Thursday, December 10, 2009

Global Aging: The *Real* Challenge of Our Times



Global aging is real, it's man made, and it threatens the health and economic prospects of the global population, especially the developing world.

Not only is global aging real, it's here now, and its effects are giving rise to a frighteningly new global phenomenon: a pandemic of chronic disease.

(1) Global aging is real.

In 1800, with nearly one billion people alive, life expectancy at birth did not surpass thirty years. By 2000, with more than six billion people alive, life expectancy reached nearly sixty-seven years amidst a continuing rise. (source). In just 200 short years we have more than doubled the average life expectancy that modern humans experienced for tens of thousands of years.

Today there are 600 million people over the age of 60. And by the middle of this century there will be 2 billion people over age 60. (source).

In Canada, for example, the proportion of seniors in the overall population has gone from one in twenty in 1921, to one in eight in 2001. The growth of the seniors population will account for close to half of the growth of the overall Canadian population in the next four decades (source).

Over the past half a century the global distribution of life expectancy has become less skewed. In 1960 the life expectancy of the world's quintile with the lowest life expectancy was 35.9. This had risen to 53 years by 1999, an increase of 48%, and is 80% of the global average. The quintile with the highest life expectancy went from a life expectancy of 70.1 in 1960 to 76.8 by 1999. This was an increase of 10%, and is 16% above the global average life expectancy (source). Despite serious challenges to increases life expectancy (like AIDS in Africa), a demographic convergence is occurring. Population aging is a global, not local, phenomenon.

(2) Aging is "man made"

There are no "aging genes". Unlike vision, dexterity or memory, which are the product of natural selection, aging is the product of evolutionary neglect. Leonard Hayflick describes aging as an artifact of civilization:

Humans are the only species in which a large number of members usually experience aging. Aging in numbers proportional to those seen in humans simply does not occur in feral animals. It occurs only in the animals that humans choose to protect.

....Because humans, unlike feral animals, have learned how to escape the causes of death long after reproductive success, we have revealed a process that, teleologically, was never intended for us to experience. One might conclude, therefore, that aging is an artifact of civilization. (source)

(3) The Moral Duty to Tackle Global Aging

The fact that populations are aging is a mix of good and bad news. On the good news end of things, global aging is an incredible and laudable accomplishment. A number of important advances -- such as technology (especially the sanitation revolution), medical knowledge, material resources, changes in behaviour, etc.- brought a rapid decline in infant, child, maternal and late-life mortality. Humans have never enjoyed the opportunities for health and longevity that they now enjoy.

However, biological aging, and population aging, bring unprecedented challenges. Aging individuals faced increased risks of morbidity and mortality. Chronic diseases like cancer, heart disease, stroke, arthritis, etc. are set to ravage the aging populations of the world. This means unprecedented numbers of humans will suffer years of frailty and disease. Chronic diseases have replaced infectious diseases as the greatest threat to global health. In the year 2005, chronic diseases killed 35 million people worldwide. That number is twice the number of deaths due to infectious diseases (including HIV/AIDS, tuberculosis and malaria), maternal and perinatal conditions, and nutritional deficiencies combined (source).

Aging populations place ever growing stress on health care and pensions.

So the scientific consensus is in: global aging is real. The data is beyond dispute.

And the scientific consensus on the impact senescence has on our health is in-- it increases one's risk of morbidity and mortality. That data is beyond dispute.

So what are we going to do about global aging? At the end of this century our children and grandchildren will look back and ask:

"What were they thinking? Did they not see how dire the consequences of global aging can be? Did they not care about protecting all future generations from the chronic diseases that ravage humans in late life? Did they not care about passing on the economic benefits of the longevity dividend? Why did they focus so much on very low-risk events, like terrorism or catastrophic global warming, and so little on the most likely of risks-- like the chronic diseases of aging?"


(4) What can we do?

Adaptation, Age retardation and Regeneration

Can we just adapt to global aging? No. There are some external modifications we can make to the our environment to promote the health and happiness of aging populations. We can re-design our cities to make them more hospitable to a population with more limited mobility. We can ensure there are public spaces, such as parks, to help promote the fitness of aging populations. We can encourage the population to keep their minds active to help delay the progression of cognitive decline and mental illness, etc.

But adaptation alone will not stop the tsunami of chronic diseases that await the 2 billion seniors that will exist in the year 2050. So what else can we do?

We can search for ways to directly modify our biology to help mitigate the harmful effects of biological aging. If we developed an aging pharmaceutical, for example, that could mimic the effects of calorie restriction we could slow human aging and this would confer health and economic dividends for all future generations to enjoy by increasing the human healthspan and compressing morbidity. We are closer to this than you might think (see this).

And we could also invest in regenerative medicine and develop new interventions that help aging populations enjoy more health and vitality.

We should be bold and imaginative in our deliberations concerning how to meet the challenges of global aging.

But before we can have a serious debate about what to do to address global aging, we must get our heads out of the clouds and acknowledge the reality of what are the most pressing and probable problems that await humanity this century. And global aging should be at the top of that list.


Cheers,
Colin

Saturday, September 26, 2009

Obesity and Aging Linked




Sometimes it is tricky to make the link between important related (even complementary) societal goals. Over the years I have emphasized the importance of tackling obesity. See, for example, my 3 part post on childhood obesity (here) or my post on how exercise can help prevent depression here.

Over the years I have also exerted a lot of energy emphasizing the importance of tackling aging itself. A search for "aging" on the search function for my blog gives this lengthy list of posts.

Many people would of course agree that obesity is a problem. And thus they would agree that we, as both individuals and societies, ought to tackle obesity in an effort to reduce the risks of heart disease, stroke, diabetes, etc.

Yet when it comes to aging I know most people's attitudes become very different. Either they think (a) talk of mitigating aging (unlike obesity) is pure science fiction (which is what I actually thought before I started to follow the scientific developments in the field); or (b) they think it is unethical to intervene in the aging process.

And so over the past few years I have spent most of time arguing against what Richard Miller calls “gerontologiphobia” which he defines as follows:

There is an irrational public predisposition to regard research on specific late-life diseases as marvelous but to regard research on aging, and thus all late-life diseases together, as a public menace bound to produce a world filled with nonproductive, chronically disabled, unhappy senior citizens consuming more resources than they produce. No one who speaks in public about longevity research goes very far before encountering the widespread belief that research on extending the life span is unethical, because it will create a world with too many old people and not enough room for young folks.

And so I have published articles arguing that sufficiency is an inappropriate principle to invoke for the good of health, I have argued that equality requires us to mitigate age-related disadvantage, I have argued that the time has come to take on time itself, I have argued that the concerns about aggregation that arise in the case of tackling aging are not valid objections to prioritizing aging research, I have argued that we need a more inclusive vision of the medical sciences, and I have argued that it is both rational and reasonable to aspire to decelerate the rate of aging.

So I think the reasons for tackling aging are many, diverse and, most importantly, compelling! And yet the struggle to overcome gerontologiphobia goes on.

Well, this article in the latest issue of Nature Medicine illustrates why the we ought to be consistent in our attitudes towards health when it comes to tackling both obesity and aging. It turns out that obesity actually accelerates aging!


Here is a brief excerpt from the News and Views section on the study:

As technology has improved hygiene, the food supply and living standards overall, there has been a rise in such age-related illnesses as cardiovascular disease, cancer, degenerative diseases of the brain and other organs, and metabolic disorders such as diabetes. Age-related disorders have become widespread throughout the world, replacing infectious diseases as the leading cause of death in developed countries. As we age, many people develop the metabolic syndrome, characterized by central (visceral) obesity, insulin resistance, impaired glucose tolerance or overt diabetes, hypertension, dyslipidemia and cardiovascular complications.

Diabetes is also a recognized cause of accelerated aging, but the mechanisms linking diabetes and aging are not well understood. Work from Minamino et al.1 in this issue of Nature Medicine offers insights into how obesity affects the aging of adipose tissue, influencing inflammation and glucose homeostasis.

...In obese states, adipose tissue is subjected to oxidative stress, resulting in aging, accumulation of macrophages, production of proinflammatory cytokines and suppression of adiponectin. Activation of p53 tumor suppressor is pivotal in the aging process, stimulates inflammation and possibly attenuates the capacity of stem cell renewal. The aging of adipose tissue induces insulin resistance in adipose tissue, liver and muscle and mediates the progression to diabetes.


And here is the abstract of the study:

Various stimuli, such as telomere dysfunction and oxidative stress, can induce irreversible cell growth arrest, which is termed 'cellular senescence'1, 2. This response is controlled by tumor suppressor proteins such as p53 and pRb. There is also evidence that senescent cells promote changes related to aging or age-related diseases3, 4, 5, 6. Here we show that p53 expression in adipose tissue is crucially involved in the development of insulin resistance, which underlies age-related cardiovascular and metabolic disorders. We found that excessive calorie intake led to the accumulation of oxidative stress in the adipose tissue of mice with type 2 diabetes–like disease and promoted senescence-like changes, such as increased activity of senescence-associated beta-galactosidase, increased expression of p53 and increased production of proinflammatory cytokines. Inhibition of p53 activity in adipose tissue markedly ameliorated these senescence-like changes, decreased the expression of proinflammatory cytokines and improved insulin resistance in mice with type 2 diabetes–like disease. Conversely, upregulation of p53 in adipose tissue caused an inflammatory response that led to insulin resistance. Adipose tissue from individuals with diabetes also showed senescence-like features. Our results show a previously unappreciated role of adipose tissue p53 expression in the regulation of insulin resistance and suggest that cellular aging signals in adipose tissue could be a new target for the treatment of diabetes.

OK, so bringing the insights of the link between obesity and aging together with attitudes towards biological aging in general... When it comes to a disease like progeria, which is an extreme form of accelerated aging, I assume we would all agree that we should seek ways of preventing the disadvantage that comes with the disease. No child deserves to be robbed of the opportunity to have a healthy childhood and develop into a healthy adult. Progeria is very rare, affecting about 1 in 8 million births.

When it comes to obesity, which also accelerates aging (though is less severe than progeria, but much, much more prevalent) we also think we should strive to prevent this. No one deserves diabetes or heart disease in their 50's or 60's. But what about the "regular" rate of aging, which is less severe but much, much more prevalent than obesity, what should our attitude be? The inborn aging process limits average life expectancy of humans to around 85. Shouldn't we aspire to retard that rate of molecular and cellular damage if it would help prevent disease and death? Does anyone actually believe people (our to make the point more vivid, their parents, children or spouse) deserve heart disease, stroke, AD, cancer, etc. in late life? The prevalence of gerontologiphobia is among the most perverse features of our culture for it eschews the most importance science of our day. These means aging research is grossly underfunded and that young scientists who want to make the world a better place gravitate towards goals like trying to control the global climate or finding a cure for just one disease of aging (e.g. cancer) rather than investigating the aging process itself.

So this study in Nature Medicine, which suggests there is a link between aging and obesity, shows why our attitude towards aging and obesity ought to be the same. Those who believe that the "obesity status quo" is unacceptable should also view the more general "aging status quo" as unacceptable. Both subject today's populations to high risks of morbidity and mortality, risks we should seek to minimize as far as possible.

Cheers,
Colin

Monday, March 02, 2009

Aging Research and Making the Future Vivid


This post is also posted on the Women's Bioethics Project here.


In this post I try to make the case for getting those interested in bioethics and issues pertaining to women to join the cause of supporting the basic science that could lead to a deceleration of human aging.

At first blush the proposition that those interested in the health and welfare of women should support aging research might sound counterintuitive. When we hear the phrase "aging research" we might automatically envision the kinds of products we currently see advertised on TV, like "anti-aging" creams that promise to restore the youthful appearance of skin, hide wrinkles, etc. Such products reinforce demeaning ideals of "womanhood"-- that a woman's self-worth can be reduced to her physical appearance and thus every woman should do everything she can to present herself as "youthful" and conceal the signs of aging. Those are not the interventions, and that is not the message, I am talking about. Far from it.

By "aging research" I mean the scientific field of biogerontology which studies the biological processes of aging. And by an "anti-aging" intervention (which is currently hypothetical... there is nothing you can currently buy that decelerates aging) I mean a pharmaceutical that decelerates the rate of molecular and cellular damage caused by aging. An intervention could do this be mimicking the effects of calorie restriction (without actually requiring a restriction of calories). A deceleration of the aging process would delay many of the common diseases and conditions associated with aging (like heart disease, cancer, stroke, AD, etc.) and possibly compress morbidity and mortality. Thus people would enjoy more years of disease-free life than that possible given the current rate of aging for most humans.

When I talk to people about my interests in this area there are a number of reservations and concerns they have. Let me briefly identify, and address, two of them: (1) many feel that talk of retarding human aging sounds like mere science fiction; and (2) many express the viewpoint that it is distasteful to worry about decelerating aging when there is so much poverty and disease in the world. I will very quickly address (1) and then focus on (2), with particular reference to the situation of women.

Talk of retarding human aging will strike many as either pure science fiction, or, at best, the prospect of an "anti-aging" pill is a long, long ways off. This is a common reaction and one that would have been more reasonable to hold 20 or even just 10 years ago. But over the past decade amazing progress has been made in the field of longevity science which makes the prospect of a genuine anti-aging pill becoming available in the next 5-10 years a real possibility. In fact there are a number of human clinical trials currently underway involving resveratrol (an anti-aging molecule present in red wine) and Sirtris has trials for more concentrated compounds.

So the first hurdle for these products is to establish if they are safe and effective treatments for the diseases of aging. If so, they could be pursued as a preventative intervention to protect people (including all future generations) from the diseases of aging. By decelerating the rate of aging during adulthood we could reduce our risk of disease and death in late life, thus extending the number of healthy years humans could expect to live.

OK, so back to my main goal of encouraging those interested in the issues facing women to champion this area of scientific research. This brings me to concern (2). One might wonder why, given all the pressing issues facing women in the world today, that they ought to add aging and longevity science to the list of things to address. "Is it really a priority?" one might ask. "Is it a priority in a world with disease and poverty?"

This is a fair question. And the answer is "YES!". Why? Because most disease in the world today is caused by aging. Now you won't find data from the World Health Organization that states that explicitly. But what you will find are the data concerning the proximate (rather that evolutionary) causes of morbidity and mortality. But behind the proximate causes of most human deaths (like cancer and heart disease) are the biological processes of aging. In other words, it is not a coincidence that most people who suffer disease and death today are over age 60. The vulnerabilities of late life reflect the tradeoff that natural selection has made between the fitness of a parent and reproduction. Natural selection favors a strategy in which organisms invest fewer resources in the maintenance of somatic cells and tissues that are necessary for indefinite survival of the individual (source).

The enormous and unprecedented disease burden the world will experience this century makes vivid the human toll of this tradeoff. Take the year 2005, the latest year that one can easily find the stats from the World Health Organization. Approximately 55 million people died in 2005. Of that number, 35 million died of chronic disease. That number is twice the number of deaths due to infectious diseases (including HIV/AIDS, tuberculosis and malaria), maternal and perinatal conditions, and nutritional deficiencies. That is a staggering figure. Furthermore, between the years 2005-2015 WHO estimates that 220 million people will die from chronic disease, most of them (144 million deaths) in lower middle income countries like China and India. The diseases associated with aging are not, contrary to popular perception, only a problem for people living in the developed world. Indeed, being vulnerable to disability and frailty is a much greater disadvantage if one lives in a poor society with no decent health care or pension, as the link between income and "ability to work" is much more direct. So the chronic diseases associated with aging are a problem for all societies, not only the richest countries in the world.

I don't want to fixate too much on the global figures for chronic disease but some brief comparisons with other events in human history will help us get a sense of the magnitude of the problem of chronic disease. It is estimated that between the mid-14th and mid-17th centuries, the "Black Death" plague killed approximately 25 million people. This means that the current deaths caused by chronic disease in just one year is equal to the number of total deaths caused by three centuries of the "Black Death" plague! The 220 million deaths caused today by a decade of chronic disease is closer to the scale of death from a few decades of small pox. In the twentieth century small pox is estimated to have killed between 300 and 500 million people. By 1980 small pox had been eradicated thanks to the small pox vaccine.

Could we vanquish chronic diseases like heart disease and cancer this century, like we did small pox last century? To make serious headway against chronic disease we must understand the ultimate (that is evolutionary) and not just proximate cause of disease. There is no virus that is responsible for all cancers, heart disease, stroke, AD, etc. But if we better understand the biological processes of aging we may be able to modify the rate of aging so that we reduce our risk of disease and death in later life. So tackling aging is an issue of preventative medicine. An anti-aging pill that slowed down the molecular and cellular damage of aging would extend the period of healthy life humans could expect to live.

In order to appreciate the great benefits this could confer upon women, especially women in poorer countries, consider the facts of this report:

Women comprise the majority of the older population in virtually all countries, largely because globally women live longer than men. By 2025, both the proportion and number of older women are expected to soar from 107 to 373 million in Asia, and from 13 to 46 million in Africa.

And.....Osteoporosis and associated fractures are a major cause of illness, disability and death, and are a huge medical expense. It is estimated that the annual number of hip fractures worldwide will rise from 1.7 million in 1990 to around 6.3 million by 2050. Women suffer 80% of hip fractures; their lifetime risk for osteoporotic fractures is at least 30%, and probably closer to 40%. In contrast, the risk is only 13% for men.

To fully appreciate the benefits of an intervention that decelerates human aging we must make the future health prospects for women in the world today more vivid. In particular we need to consider what the situation of those vulnerable today will be in the decades to come-- like the 373 million older women who will be living in Asia by 2025. These women will be vulnerable to the chronic diseases and disabilities of aging. But we could reduce these risks if we could decelerate human aging.

One of my favourite Ted Talks lectures is this one by Harvard psychologist Dan Gilbert. It is a brilliant presentation, outlining how our decisions are skewed by a variety of limitations and biases.

At the end there is an apt question from biogerontologist Aubrey De Grey concerning how these cognitive limitations impact our ability to see aging for the threat that it actually is. Gilbert responds by noting that humans can imagine the near future much more vividly than the far future. That is why we are more likely to address the problems of today rather than those of tomorrow. And this is a real problem for humanity given that the health problems facing 2 billion persons over age 60 by 2050 will be enormous.

To get people to make more sage decisions about the far future we need to provide them with details. We need to help them become psychologically connected with the future. The more detail people have about the far future the more likely they will make decisions about it like they do the near future (though we don't always do the latter well either, but that is the subject for another post! :)).

So my plea for getting those interested in women's health and welfare to get behind aging research is one that seeks to make vivid the threat that senescence poses to the health prospects of women this century. Senescence will likely cause more disease and disability for women this century than any other cause. Senescence not only threatens our health and survival by increasing the risk of fatal diseases (like heart disease and cancer), but also one's ability to contribute to their communities and families. Aging research is thus a vital component of developmental economics. The sooner we increase public support and funding for this science, the sooner we will be able to reduce the risk of morbidity and mortality for the world's aging female populations.

Cheers,
Colin

Monday, October 20, 2008

Why Worry About Aging?




Humans are vulnerable to seemingly endless intrinsic and extrinsic risks. Consider for a moment the multitude of environmental risks we face each day. These range from being in a traffic accident and consuming contaminated food we purchased at the grocery store or a restaurant to being assaulted or falling down a stairway.

Taking some risks is unavoidable. Locking oneself inside their home all day will not insulate one from risks of harm. For such behaviours have their own risks- like malnourishment, muscle atrophy and jeopardizing one’s mental health! Furthermore, no one lives on an isolated island like Robinson Crusoe. So even one’s home is only as safe as one’s neighbourhood... country... planet.

Given the diverse and pervasive nature of the risks facing any given population, we need to think clearly and rationally about managing these risks. As individuals, we must consider the consequences of our lifestyle- like our diet and physical activity. These actions can have a dramatic impact (for better or worse) on our health prospects. And governments must prioritize the various policies they could pursue to protect and improve the health prospects of the population.

Given the magnitude of the stakes involved in these kinds of deliberations about risk, it should be apparent that such deliberations are among one of the most important things individuals and societies could do. For if we invest all our energies into tackling the smallest and most trivial of risks, we then leave ourselves vulnerable to the most probable and costly of harms. Tragically, we do not do a good job of thinking rationally about risk (see this great book, for example).

Examples of the errors we commonly make about thinking sensibly and consistently about risks are all too common. For example, think of the case of an overweight smoker who decides to stop consuming anything with aspartame because they are worried about its possible adverse effects on their health. Or a mother who smokes while pregnant and then worries about having her child immunized for fear that it will cause her child to develop autism.

And governments do not always fare much better. Recall this post and the obsession the Bush Administration has paid to reducing the likelihood that any American will die from terrorism. And yet this Administration has done little to prevent the 300,000 deaths a year associated with obesity and excess weight, or the 400,000 deaths a year associated with cigarette smoking. And while global action to tackle climate change often dominates the news, there is little attention paid to things that could actually aid the globally disadvantaged now (and for little cost), like providing bed nets for malaria and removing farming subsidizes.

There is a vast array of empirical research that examines how individuals and groups reason poorly about tackling risks. These range from problems of limited knowledge and biases to group polarization. I am now spending a good deal of my time reading this literature and doing so has proved very useful in bringing together diverse threads of my academic research. Here I will mention just one- the importance of aging research.

When people ask me what I am working on I inevitably mention aging and the aspiration to retard human aging. This provokes many different responses. The most common response is a sense of surprise that we might actually be able to do something about aging. This is of course understandable, for if one had not been following the field of biogerontology for the past few years one might assume that aging is immutable, for that was a common belief. But this belief has been proven wrong- aging is not immutable.

Once I note this people often persist in their scepticism, and express doubt that we could actually develop a technology that could slow aging in humans (rather than just in mice). Again, this scepticism is understandable, indeed some scepticism is warranted. But I often ask them how much scepticism they have about finding a cure for cancer, or reversing climate change. And when it comes to these issues they are pretty optimistic about the likelihood that these goals could be achieved.

So I push them a bit further... and it becomes evident that this optimism is not based on any scientific experiments that demonstrate a particular therapy could cure all 200+ types of cancer, or that climate experiments demonstrated that we could reverse the rise in global temperature. What their optimism is based upon is the desire to achieve these things, that they would create enormous benefits for humanity. Again, I understand the appeal of this line of thinking. We want to believe that we can achieve those things that would really do a lot of good in the world.

Well, when it comes to aging the good news is there is an even sounder scientific basis for thinking we could actually retard human aging AND the magnitude of these benefits (say slowing aging by just 7 years) would be even bigger than a cure for cancer or reversing climate change. And so these points provide all the more reason for getting behind longevity science!

And so this takes me to the title of this post- “Why Worry About Aging?” Well, let me give you a few reasons. Firstly, we should worry about aging because aging is one of the biggest risks factors for death and disease in the world. Odds are, most people you know who have died in your lifetime were older than you are. This is not just a coincidence! Aging increases the risks of morbidity and mortality. After age 28, your risk of death increases almost exponentially. Biodemographers estimate that every 7 years during your adult life your risk of frailty, disability and death doubles. That is a very sobering insight!

So given the magnitude of the harms of aging, coupled with the fact that scientists have made incredible advances in understanding the biology of aging (like which genes can increase the lifespan of a species), you would expect everyone to be worried about aging. Is this so? My own sense is that this story is mixed and complex.

As individuals, few adults are overjoyed with the fact that they have aged yet one more year every time they celebrate a birthday. In fact, I think it is only children who really *celebrate* a birthday. Most adults grumble and complain about getting older. They would prefer not to be reminded of how old they are with a cake filled with a wide stack of candles.

And so at some level everyone knows, to some degree, that aging is a big problem for them as individuals. No one enjoys the fact that their risk of cancer, heart disease, stroke, AD, etc. will continue to rise for all of their remaining years. When in certain moods, we can all admit this. But we don’t want to go on and on about it every day. It’s depressing! And so we tend to bury these feelings deep inside and go on with our daily activities wearing “aging-blinders”.

And so we find there is an enormous disconnect between what the public actually demands of their governments- like protection from terrorists, tackling abortion , etc.- and what would actually substantively improve their lives. If you really want government to reduce your chances of death and disease, then get behind aging research. If there was no chance that scientists could actually develop a drug or intervention that could modify the rate at which the molecular and cellular damage of aging occurs then it would be cruel to tell people to “worry about aging”. But given where the science actually is, it is irrational and irresponsible *not* to tell them to worry about aging. Especially when people fear so many things that really do not pose a great threat to their health and well being.

And this highlights another challenge for longevity scientists- trying to motivate people to get behind aging research by telling them they have good reason to worry about aging, and yet at the same time not depressing people so much that their mental health is jeopardized! So I don’t subscribe to instilling “fear of aging”. Fear is usually the enemy of sound, responsible policy-making. But I admit that walking the “worry about aging” line is a challenging and fine line to tread.

People are often very disturbed when I start telling them about the realities of aging; like how it increases our risks for disease and death. They wonder how I sleep a night. They fail to see that my concern with aging is not primarily driven by a concern about my own health prospects (though of course I do care about that), but rather about the impact aging will have on the future of humanity. Senescence will cause more disease and death this century than anything else. What does trouble me most at night is that fact that we invest very little in the science that could actually substantively improve the life prospects of those living in both poor and rich countries.

And so I think more public discussion of why would should worry about aging can be a good thing. The way I look at it is like this- we all worry about something. And it is best to worry about those things that (a) are really a big (rather than small) problem and (b) are problems we could actually do something about. Once you realize there is a scientific basis for believing that aging satisfies (b), then you will want to get people more worried about aging and supporting aging research.

Cheers,
Colin

Saturday, May 30, 2009

The Availability Heuristic and the Inborn Aging Process


Two weeks ago I gave a new paper entitled "Why Aging Research? The Moral Imperative to Retard Human Aging" to a group of scientists who work on biomedical gerontology at this conference in Quebec.

This talk was a unique experience for me as it was the first time I gave a talk to an audience where most people believe that (a) aging is a serious health problem, and (b) it is a problem we can actually do something about.

Why is it the case that this particular audience, unlike most audiences I address, hold beliefs (a) and (b)? The answer is simple- because this audience was composed of scientists who spend their lives studying and manipulating the biological processes of aging. So they are well aware of what happens to the biology of different species as they age, and the different kinds of interventions (e.g. dietary restriction, genetic manipulation, etc.) that can modulate the rate of aging.

Over the 3 days of the conference I met many interesting people, listened to some fascinating talks about experiments on worms, mice, and flies, and also had fascinating philosophical debates about aging and the "good life". In fact this conference was among one of the most enjoyable and rewarding conferences I have ever attended.

While at the conference I met people involved with the LifeStar Institute, and was invited to join their list of advisors. I was happy to accept, and urge you to watch the compelling and moving video on their web site.

Over the past few weeks I have also been busy making revisions to the paper that this talk is based on. And in this post I would like to bring together many of the thoughts I have been pondering. So, down to the details....

Here is a thought experiment:

Rank, from the most probable to the least probable, the following list of risks of mortality:

1. You and your loved ones will die from climate change.
2. You and your loved ones will die from a terrorist attack.
3. You and your loved ones will die from cancer.
4. You and your loved ones will die from a stroke.
5. You and your loved ones will die from Alzheimer's Disease.
6. You and your loved ones will die in a car accidence.
7. You and your loved ones will die from homicide.
8. You and your loved ones will die from pollution.
9. You and your loved ones will die from a poor diet.
10. You and your loved ones will die from the inborn aging process.

Once you have come up with your rankings, do the ranking again, but this time change the content of the first part of each sentence so it reads:

"Most people living in the world today will die from...."

These two tests do many things. Firstly, they test how accurate (or rather inaccurate) our intuitions about the major risks of mortality that we and our loved ones face are with the facts. Secondly, they test how accurate our intuitions are about the risks that face humanity as a whole.

One risk factor on this list is by far the greatest risk factor to your health, the health of your children and loved ones, and the health of the world's population-- aging (which is also implicated in risks 3,4, and 5).

I know, I know, many are sceptical about this claim. "If aging kills so many people, how come the Centre for Disease Control doesn't list aging as the leading cause of death?", you might reasonably ask. My short reply: "Because the current classifications for death, as is explicit in the title of the CDC, focuses exclusively on the proximate (e.g. specific diseases) rather than ultimate causes of mortality".

Most deaths in the world today (see here and here) are caused by chronic disease (like cancer, heart disease and stroke). And most chronic diseases afflict people in late life (over age 60). Why is this the case? Why do most cancer deaths, strokes, heart attacks, etc. occur after the sixth decade?

Evolutionary biology provides the answer. Most people alive today will die from the chronic diseases of aging. And the ultimate cause of this situation is evolutionary neglect. The inevitability of death due to hazardous external environments (e.g. predation, starvation, etc.) means that reproduction is made a higher biological priority than is indefinite maintenance. Natural selection does not influence the post-reproductive period of the human lifespan, hence why our bodies and minds begin to fall apart when they do.

But there is another problem. Because evolutionary neglect is not something we can directly observe (unlike melting polar ice caps and 9/11 terrorist attacks), few perceive the current rate of aging for the problem that is really is. No one walks into a nursing home and says: "Well, it is evident that evolutionary neglect has really left the human species vulnerable to frailty and disease in late life, let's do something about this!". The media does not report gripping stories on the impact evolutionary neglect has on scarce health care resources. Nor do politicians get elected by promising to combat the effects of evolutionary neglect. This is a problem, a big problem. It means we end up neglecting the leading cause of disease and death in the world. That's a perverse situation. Indeed, it's harder to think of a more perverse situation! And this is why I have dedicated so much of my research and energies into trying to help raise greater awareness about these issues.

In a rational world, aging research would be at the forefront of a global collaborative initiative to improve the health and economic prospects of today's aging populations (and all future generations).

But humans are not rational. We suffer many cognitive biases. One prominent bias is the availability heuristic. Risks that are easily brought to mind are given a higher probability; and conversely, the less vivid a risk, the more likely we are to underestimate the probability of their occurring.

The two tests above reveal how prominent this heuristic is in your own comprehension of the risks facing yourself, your loved ones and humanity. Because death by aging is not something that is vivid is most people's minds (though it is in the minds of the scientists who study the biology of aging and thus know all too well how it affects a species functional capacities), odds are you probably underestimated it as a risk of mortality. When you attempt to picture the scenario of someone dying from aging you probably picture a peaceful, painless death- perhaps a centenarian who, while asleep, suffers heart failure and dies immediately. Sadly this is not the reality. Very few humans have the "longevity genes" that centenarians have. Most people have the genes typical of the adults who populate nursing homes. The only thing separating you from them is the number of years you have been alive. Normal aging entails a period of chronic disease, which means a prolonged period of painful, and expensive, existence.

The reality is that almost everyone you and I know will die from the chronic diseases caused by the inborn aging process. This means your children will probably die from the same diseases that killed your parents and grandparents.

If there was nothing we could do to alter this state of affairs then it would be depressing and pointless to go on about all this. But we now know that ageing is not immutable. Humans do not have to endure the disease and frailty that the current rate of aging imposes on us. Retarding aging would add more years of health and compress morbidity at the end of life. The goal of age retardation is thus among one of the greatest priorities for humanity this century.

Sadly, not only does the availability heuristic impair our ability to perceive the risks of the inborn aging process, but it also impairs our ability to accurately evaluate the magnitude of the benefits of age retardation.

Here is another thought experiment:

Imagine what would happen if a safe and effective drug was developed that could retard human aging (by mimicking calorie restriction), thus adding 20-30 years to the human healthspan. What would the consequences of this be?

Many people's intuitions immediately gravitate towards negative consequences that can easily be make vivid in their minds- like global overpopulation and growing health inequalities between the rich and poor. But these consequences, which come up a lot in discussions of these issues, are not premised on empirical evidence. They are based on the availability heuristic.

So what are the most likely consequences of a drug that retards human aging? Well, like immunizations- that have helped reduce early-life morbidity and mortality- the most obvious consequence would be a reduction in late-life morbidity and mortality. Fewer people would get cancer, have a stroke, suffer from arthritis, be frail, suffer from dementia, suffer bone fractures, burden their families by requiring constant care, etc. So the population would be healthier and economies would flourish. But these realities are much harder to make vivid in our minds than the imagined negative consequences. It is so much easier to imagine worst case scenarios, even if they have no basis in reality. And this impedes some of the most important scientific advancements of our time.

Thus two distinct legacies of our evolutionary history present formidable challenges. The first, the inborn aging process, causes most disease and death in the world. And given how many aged people there are in the world (600 million over age 60 today, and this will rise to 2 billion by 2050) the inborn aging process will kill, for the first time ever, more people this century than any other cause. Each year chronic disease kills more people than three centuries of the "Black Death" plague killed.

The second legacy of our evolutionary history are cognitive biases, like the availability heuristic. We have evolved to perceive risks through our five senses. So a charging tiger is easily perceived as a risk. But evolutionary neglect is not. To make serious headway against aging we must also make serious headway against the faulty heuristics we commonly premise our decision-making on.

If you really care about the future your children will inherit from us, then I urge you to join the battle against chronic disease and the battle against irrationality. And championing the cause of aging research is at the forefront of both of these battles. Our children do not have to suffer the same fate that our parents and grandparents suffered in late life. Please support the science that could help reduce most disease and death in the world. Please support aging research.

Cheers,
Colin

Thursday, October 01, 2009

International Day of Older Persons (2009)



October 1st is International Day of Older Persons. See the WHO website here.

There is no better day to promote the importance of aging research than on this day. If we want to promote the health and economic prospects of the world's aging populations then we must get serious about the science which seeks to understand, and then ameliorate, the aging process itself.

Below I re-post three important entries that are appropriate on this day.

The first, originally posted in November 2008, is entitled "Ten Things You Probably Didn’t Know (But Should) About Aging".

The second post, entitled "Idealism Meets Realism: Tackling Chronic Disease Via Age Retardation" was posted in June 2009.

The third and final post, entitled "The Availability Heuristic and the Inborn Aging Process", was originally post in May 2009. Enjoy!

Cheers,
Colin


"Ten Things You Probably Didn’t Know (But Should) About Aging"



Why, you might wonder, would a philosopher and political theorist spend so much time worrying about aging (see here, here and here)?

Well, because I believe aging is the most important neglected issue of our time! If you don't believe me, consider the following ten facts about aging you probably didn't know:


1. The inborn aging process is now the major risk factor for disease and death after around age 28 in the developed countries and limits average life expectancy at birth to approximately 85 years (source).

2. Why do we age? Aging occurs because natural selection favors a strategy in which organisms invest fewer resources in the maintenance of somatic cells and tissues that are necessary for indefinite survival of the individual. (source)

3. Aging is not immutable. The lifespan of organisms such as worms, flies, and mice can be extended by restricting food intake. And experiments with the fruit fly Drosophila melanogaster have demonstrated that their lifespan can be doubled by delaying reproduction over generations. (source) Castration of salmon (source) and humans (source) can also extend lifespan.

4. Approximately 1 in 10 000 Americans are centenarians (source). Having a centenarian sibling increases one’s chances of survival to very old age. (source). The FOXO3A genotype is strongly associated with human longevity (source).

5. The first human clinical trials for an anti-aging molecule began this year. (sources here and here)

6. If you live to 95, you actually stop aging! (but have a very high risk of mortality) (source)

7. In the two hundred years from 1800 - 2000, life expectancy at birth in the world increased from below 30 to 67. (source).

8. There are approximately 600 million persons aged 60 years and over; this total will double by 2025 and will reach virtually two billion by 2050 - the vast majority of them in the developing world. (source) October 1st is the International Day of Older Persons.

9. Despite the fact that the vast majority of the world's 6.5+ population will die from age-related causes, aging research is underfunded. In the year 2006, the National Institutes of Health was funded at $28 billion and yet less than 0.1% of that funding was spent on understanding the biology of aging. (source)

10. Even a modest deceleration in human aging could be this century’s most important medical intervention. Furthermore, there is a sound scientific basis for believing this could be achieved. We are closer to this goal than we are to eliminating cancer or heart disease. Furthermore, age retardation could yield health dividends far greater than those that would be achieved by the elimination of any specific disease of aging. This is the case because of the fact of co-morbidity. This means that eliminating all cancers would only add a few years to life expectancy as one of the other afflictions of senescence would soon ravage an aged person (e.g. heart disease, stroke, diabetes, AD, etc.). So delaying all these afflictions is much more important than eliminating just a couple of them.


"Idealism Meets Realism: Tackling Chronic Disease Via Age Retardation"



An idealist is one who aspires to bring about a better state-of-affairs than those realized in the status quo.

The idealist looks at the world around them and says: "Things could be better, things should be better. Let's get it done".

Most of us are idealists about some things. The world needs more idealists.

A realist is one who grounds their aspirations in an understanding of the constraints of reality.

The realist looks at the world around them and says: "While we might not always like the ways things are, we should not forget how bad things used to be and how difficult (and sometimes fleeting) positive change can be. Meaningful progress can be made, but it takes time and much more than good intentions."

Most of us are realists about some things. The world needs more realists.

When I reflect on my own beliefs and aspirations I realize how intricate and complex this balance of idealism and realism is. There are some things I am an idealist about, and some things I am a realist about.

When I hear someone championing a cause that perhaps coheres with my idealist sensibilities, but clearly violates my realist sensibilities, I usually categorize their aspirations (after a thorough re-examination of my own realist and idealist sensibilities!) in the "naive utopian" pile of ideas.

Conversely, when I hear someone making a pragmatic argument that is perhaps sympathetic to my realist sensibilities but contravenes my idealist sensibilities, I usually categorize their aspirations (after a thorough re-examination of my own realist and idealist sensibilities!) in the "too conservative and unimaginative" pile of ideas.

The tension between my idealism and my realism helps keep my goals and aspirations in check. I don't espouse ideals that I think are unrealistic (like control of the global surface temperature) nor are my ideals tempered by realist constraints that I genuinely believe are not, in the long run, insurmountable.

Between the extremes of the cockeyed idealist and the short-sighted and unimaginative realist lies the tenuous temperate of the "realistic idealist".

The idealist in me aspires for a world with less disease. Such a world would provide humans with greater opportunities to flourish: more opportunities to love, to play, to spend time with friends and family, to cultivate new interests, etc.

A world with less disease is a world with more health. Many things impede the ideal of a more healthy world- poverty, infectious diseases like HIV and malaria, inactive lifestyles, etc. And so the idealist in me recognises that many, many things must be done to make the world a more healthy world. There is no single, "silver bullet" solution to all the risks of morbidity that humans face in the world today.

The realist in me then thinks: OK, let's take this ideal a bit further by prioritizing among the various things that could be done to improve the health prospects of humanity. To do this we must ask two important questions:

(1) what causes most disease in the world today?

and

(2) what are the most likely, and cost-effective, interventions that would yield the most significant health dividends?

The idealist in me can't help but admit that these realist sensibilities are important considerations. So I agree to incorporate these empirical considerations into my "big picture" grasp of the challenges, and potential solutions, to the world's health problems.

So let's consider the first question: what causes most disease in the world today? Well, if we head over to the World Health Organization we realize that most disease-related deaths are caused by chronic diseases. In the year 2005, 55 million people died, and chronic diseases were responsible for 35 million of these deaths. That number is twice the number of deaths due to infectious diseases (including HIV/AIDS, tuberculosis and malaria), maternal and perinatal conditions, and nutritional deficiencies combined.

OK, so these real-world facts make it clear that, among the problems facing the health prospects of humanity, chronic disease is a BIG problem. And it is not a problem just for the richest countries (as many naive idealists assume). In fact, most deaths from chronic disease occur in more populous lower-middle income countries, like China and India. WHO estimates that between 2005 and 2015, 220 million people will die from chronic illness, and a 144 million of these deaths will be in these lower middle income countries.

These numbers are sobering. Never before in human history have so many people been ravaged by chronic diseases. And chronic diseases do not kill people quickly, they are long-lasting, leading to years of pain and suffering, disability and often financial hardship for families and rising health care costs.

When the idealist in me sees the data on chronic disease I say: "Things could be better, things should be better".

But how do we best combat chronic disease? While the idealist in me hopes we can make progress with treating chronic diseases, the real ideal would be to prevent them from developing in the first place. But unlike communicable diseases, which can be prevented by things like vaccinations, bed nets and condoms, chronic diseases are more difficult to prevent. There are things people can do, like quit smoking, eat a decent diet and exercise. But is there something else we should also consider?

Perhaps we are overlooking something? Something so obvious that it might have been easy to overlook? hmm... Let's back up and reflect on the fact that, historically, very few people developed, let alone died from, chronic disease. The tsunami of chronic disease that now exists is a novel development in human history. What really caused this tsunami? What explains why the 21st century is the century of chronic disease? Is it something that people now eat that is causing all these chronic diseases? Is it something in the lifestyles we now live? No.

There is one obvious reason why chronic diseases are the leading cause of death in the world: because people are living longer. Most chronic diseases are in fact caused by the inborn aging process. A 20 year-old smoker has less risk of developing cancer in the next 10 years than does a 80 year-old who never smoked in his life. And a 20-year old who eats a poor diet and rarely exercises has a greater chance of living another decade than does an 80 year-old who eats a good diet and exercises every day. The impact of smoking and inactivity pale in comparison to the impact a few extra decades of senescence has on a person's health prospects.

Maybe we have been looking in the wrong place in terms of identifying the leading causes of chronic disease. Perhaps, unlike communicable diseases that have proximate causes we can (now) easily identify- like the HIV virus and bacterium Vibrio cholerae- the real culprit to study and mitigate with chronic disease is the ultimate (rather than proximate) cause.

The vast majority of people who die from chronic disease are over the age of 60. Why does the number of years you have lived have such a strong bearing on your risk of chronic disease? The answer to this question requires us to go beyond the findings of epidemiology and the fixation on proximate causes. We need to invoke the findings of biodemography. Biodemography is the scientific study of common age patterns and causes of death observed among humans and other sexually reproducing species and the biological forces that contribute to them (source).

You might wonder why you haven't heard about biodemography before. Well, it's a relatively new new scientific discipline, just a few decades old. You might also wonder why the CDC or WHO don't invoke the ultimate causes of morbidity and mortality in their classifications of human deaths? That's a good (and very important) question. My guess is that it is simply a case of inertia. The conceptual tools and empirical insights that proved useful in helping us combat communicable diseases are still being applied (with some, but limited, success) to chronic diseases. In time this will, hopefully, change [this is my idealist speaking now!]. To change it doctors need to learn about evolutionary biology, we need to fight for science, .... well... I digress....

So what causes most chronic disease in the world today? The short answer is: evolutionary neglect. Reproduction was made a higher biological priority rather than indefinite maintenance. The post-reproductive period of the human lifespan, unlike the pre-reproductive and reproductive periods, is not influenced by natural selection. Hence why our hair turns gray, our skin wrinkles, our joints ache, and, eventually, we develop one or more chronic diseases and die.

Now let's turn to the realist question #2: what can be done? The idealist in me would see no point in listening to all the points listed above if there was no possible good news at the end of the day!! So, the short answer: we need to re-programme the human metabolism. But we must aspire to do more than follow the simple advice given by your doctor (e.g. eat sensibly and exercise, which of course everyone should do!). Lifestyle modifications alone will not be sufficient to make serious headway against the diseases of aging.

To achieve the latter we must develop a drug that mimics the effects of calorie restriction (CR). CR (unlike exercise alone) has been shown to extend the lifespan of a variety of organisms, including mice, by retarding aging, thus delaying and preventing the progression of the diseases that would otherwise have killed them sooner.

What would the development of such an "anti-ageing" drug mean for humans? It would mean that by taking a daily pill (call it the "vitality vitamin") one could reduce their risk of all age-related diseases and disorders. It would extend the number of years of health and vigour that people could expect to enjoy. Humans with a re-programmed metabolism might have the health and vitality of today's 50 year-olds even when they celebrate their 80th birthday! And when their health does seriously decline as they approach 110-120 years old, the period of morbidity would be compressed compared to what that period is under the current rate of aging.

Such an intervention is currently being tested in human clinical trials (see here). So the realist in me says "hey, this is not as far fetched as most people might think!). These trials will see if such an intervention is a safe and effective treatment for the diseases of aging. If it is, then the prospect of taking such a pill as a preventative measure, by retarding the rate of aging, is on the table.

Given where the science already is, with more support and a serious push perhaps today's adults could expect to add a decade of healthy life and compress morbidity at the end of life. And for the children of today, its conceivable that just over 3 decades of extra disease-free life could be enjoyed, compared to what the current rate of aging offers.

So what is a "realistic utopia" for the 21st century? In my view, it is a world where our children do not have to suffer the late-life morbidity that our parent's generation suffered. Age retardation would increase the human health span and compress morbidity at the end of life. This would constitute incredible progress towards my ideal of a world with more opportunities for health (though we would still need to tackle poverty and infectious disease). A world of humans with re-programmed metabolisms would mean a world where people can spend more time with loved ones and friends, more time learning about this fascinating world and universe, more time playing, and..... it would also create enormous economic benefits.

Few people in the world today believe that decelerating human aging is (a) possible and (b) an important priority. So the realist in me knows that it will be a difficult battle to fight for the realization of this ideal. But progress is being made towards this ideal as I write these words. Below are a few random links worth visiting to just get a brief glimpse of the fascinating research being done on aging. These kinds of research could lead to applied gerontological interventions that help treat and prevent the chronic disease of aging.

One... Two... Three... Four... Five... Six... Seven... Eight... Nine... Ten... and the list goes on.... [and I can't leave this important one off the list!]

Championing the cause of age retardation reflects my stance as a "realistic idealist". The most plausible and effective way to really tackle chronic disease is to delay their onset via retarding the rate of the inborn aging process. We can already do this for a vareity of organisms, including mammals like mice and monkeys. So let's do it for humans! Let's leave future generations something that will really improve their lives. Let's leave them a re-programmed metabolism that picks up the slack left by evolutionary neglect.

Cheers,
Colin

"The Availability Heuristic and the Inborn Aging Process"




Two weeks ago I gave a new paper entitled "Why Aging Research? The Moral Imperative to Retard Human Aging" to a group of scientists who work on biomedical gerontology at this conference in Quebec.

This talk was a unique experience for me as it was the first time I gave a talk to an audience where most people believe that (a) aging is a serious health problem, and (b) it is a problem we can actually do something about.

Why is it the case that this particular audience, unlike most audiences I address, hold beliefs (a) and (b)? The answer is simple- because this audience was composed of scientists who spend their lives studying and manipulating the biological processes of aging. So they are well aware of what happens to the biology of different species as they age, and the different kinds of interventions (e.g. dietary restriction, genetic manipulation, etc.) that can modulate the rate of aging.

Over the 3 days of the conference I met many interesting people, listened to some fascinating talks about experiments on worms, mice, and flies, and also had fascinating philosophical debates about aging and the "good life". In fact this conference was among one of the most enjoyable and rewarding conferences I have ever attended.

While at the conference I met people involved with the LifeStar Institute, and was invited to join their list of advisors. I was happy to accept, and urge you to watch the compelling and moving video on their web site.

Over the past few weeks I have also been busy making revisions to the paper that this talk is based on. And in this post I would like to bring together many of the thoughts I have been pondering. So, down to the details....

Here is a thought experiment:

Rank, from the most probable to the least probable, the following list of risks of mortality:

1. You and your loved ones will die from climate change.
2. You and your loved ones will die from a terrorist attack.
3. You and your loved ones will die from cancer.
4. You and your loved ones will die from a stroke.
5. You and your loved ones will die from Alzheimer's Disease.
6. You and your loved ones will die in a car accidence.
7. You and your loved ones will die from homicide.
8. You and your loved ones will die from pollution.
9. You and your loved ones will die from a poor diet.
10. You and your loved ones will die from the inborn aging process.

Once you have come up with your rankings, do the ranking again, but this time change the content of the first part of each sentence so it reads:

"Most people living in the world today will die from...."

These two tests do many things. Firstly, they test how accurate (or rather inaccurate) our intuitions about the major risks of mortality that we and our loved ones face are with the facts. Secondly, they test how accurate our intuitions are about the risks that face humanity as a whole.

One risk factor on this list is by far the greatest risk factor to your health, the health of your children and loved ones, and the health of the world's population-- aging (which is also implicated in risks 3,4, and 5).

I know, I know, many are sceptical about this claim. "If aging kills so many people, how come the Centre for Disease Control doesn't list aging as the leading cause of death?", you might reasonably ask. My short reply: "Because the current classifications for death, as is explicit in the title of the CDC, focuses exclusively on the proximate (e.g. specific diseases) rather than ultimate causes of mortality".

Most deaths in the world today (see here and here) are caused by chronic disease (like cancer, heart disease and stroke). And most chronic diseases afflict people in late life (over age 60). Why is this the case? Why do most cancer deaths, strokes, heart attacks, etc. occur after the sixth decade?

Evolutionary biology provides the answer. Most people alive today will die from the chronic diseases of aging. And the ultimate cause of this situation is evolutionary neglect. The inevitability of death due to hazardous external environments (e.g. predation, starvation, etc.) means that reproduction is made a higher biological priority than is indefinite maintenance. Natural selection does not influence the post-reproductive period of the human lifespan, hence why our bodies and minds begin to fall apart when they do.

But there is another problem. Because evolutionary neglect is not something we can directly observe (unlike melting polar ice caps and 9/11 terrorist attacks), few perceive the current rate of aging for the problem that is really is. No one walks into a nursing home and says: "Well, it is evident that evolutionary neglect has really left the human species vulnerable to frailty and disease in late life, let's do something about this!". The media does not report gripping stories on the impact evolutionary neglect has on scarce health care resources. Nor do politicians get elected by promising to combat the effects of evolutionary neglect. This is a problem, a big problem. It means we end up neglecting the leading cause of disease and death in the world. That's a perverse situation. Indeed, it's harder to think of a more perverse situation! And this is why I have dedicated so much of my research and energies into trying to help raise greater awareness about these issues.

In a rational world, aging research would be at the forefront of a global collaborative initiative to improve the health and economic prospects of today's aging populations (and all future generations).

But humans are not rational. We suffer many cognitive biases. One prominent bias is the availability heuristic. Risks that are easily brought to mind are given a higher probability; and conversely, the less vivid a risk, the more likely we are to underestimate the probability of their occurring.

The two tests above reveal how prominent this heuristic is in your own comprehension of the risks facing yourself, your loved ones and humanity. Because death by aging is not something that is vivid is most people's minds (though it is in the minds of the scientists who study the biology of aging and thus know all too well how it affects a species functional capacities), odds are you probably underestimated it as a risk of mortality. When you attempt to picture the scenario of someone dying from aging you probably picture a peaceful, painless death- perhaps a centenarian who, while asleep, suffers heart failure and dies immediately. Sadly this is not the reality. Very few humans have the "longevity genes" that centenarians have. Most people have the genes typical of the adults who populate nursing homes. The only thing separating you from them is the number of years you have been alive. Normal aging entails a period of chronic disease, which means a prolonged period of painful, and expensive, existence.

The reality is that almost everyone you and I know will die from the chronic diseases caused by the inborn aging process. This means your children will probably die from the same diseases that killed your parents and grandparents.

If there was nothing we could do to alter this state of affairs then it would be depressing and pointless to go on about all this. But we now know that ageing is not immutable. Humans do not have to endure the disease and frailty that the current rate of aging imposes on us. Retarding aging would add more years of health and compress morbidity at the end of life. The goal of age retardation is thus among one of the greatest priorities for humanity this century.

Sadly, not only does the availability heuristic impair our ability to perceive the risks of the inborn aging process, but it also impairs our ability to accurately evaluate the magnitude of the benefits of age retardation.

Here is another thought experiment:

Imagine what would happen if a safe and effective drug was developed that could retard human aging (by mimicking calorie restriction), thus adding 20-30 years to the human healthspan. What would the consequences of this be?

Many people's intuitions immediately gravitate towards negative consequences that can easily be make vivid in their minds- like global overpopulation and growing health inequalities between the rich and poor. But these consequences, which come up a lot in discussions of these issues, are not premised on empirical evidence. They are based on the availability heuristic.

So what are the most likely consequences of a drug that retards human aging? Well, like immunizations- that have helped reduce early-life morbidity and mortality- the most obvious consequence would be a reduction in late-life morbidity and mortality. Fewer people would get cancer, have a stroke, suffer from arthritis, be frail, suffer from dementia, suffer bone fractures, burden their families by requiring constant care, etc. So the population would be healthier and economies would flourish. But these realities are much harder to make vivid in our minds than the imagined negative consequences. It is so much easier to imagine worst case scenarios, even if they have no basis in reality. And this impedes some of the most important scientific advancements of our time.

Thus two distinct legacies of our evolutionary history present formidable challenges. The first, the inborn aging process, causes most disease and death in the world. And given how many aged people there are in the world (600 million over age 60 today, and this will rise to 2 billion by 2050) the inborn aging process will kill, for the first time ever, more people this century than any other cause. Each year chronic disease kills more people than three centuries of the "Black Death" plague killed.

The second legacy of our evolutionary history are cognitive biases, like the availability heuristic. We have evolved to perceive risks through our five senses. So a charging tiger is easily perceived as a risk. But evolutionary neglect is not. To make serious headway against aging we must also make serious headway against the faulty heuristics we commonly premise our decision-making on.

If you really care about the future your children will inherit from us, then I urge you to join the battle against chronic disease and the battle against irrationality. And championing the cause of aging research is at the forefront of both of these battles. Our children do not have to suffer the same fate that our parents and grandparents suffered in late life. Please support the science that could help reduce most disease and death in the world. Please support aging research.

Cheers,
Colin

Tuesday, October 28, 2008

Why Worry About Aging? (Part 2)


This post continues the issues addressed in this earlier post.


While we face an almost infinite array of risks to our health and survival, it is important to recognize the fact that not all risks of harm are equal.

Some risks of harm have a very low probability of being realized (like being hit by lightening, which is around 1 in 10 000 000). Other risks have a high probability (like risk of dying from cancer, which is almost 1 in 4 for males, and 1 in 5 for females, in the U.S.).

Some risks concern harms that are minor (like your washing machine breaking). Other risks concern things that are very severe (like disease and death).

As a species we have evolved ways of avoiding some risks. For example, if you inadvertently place your hand on a hot stove your body will quickly process the danger and send the message to your brain in the form of “PAIN! MOVE HAND! QUICKLY!”. And if you cut your arm a complex process of “wound healing” will be set in motion. Inflammatory leukocytes will be sent to the wound site to protect against infection, and different tissue and cell behaviors will be triggered by the genes we have inherited from living in a world prone to mammalian skin wound.

And as a society we have adopted measures (like laws) to avoid some risks. For example, in the province of Ontario wearing a seat belt is the law. It wasn’t always the law. However, empirical evidence showed that the risk of serious injury and death (like putting your head through the windshield) could be reduced by wearing a seat belt. And now we all wear seat belts.

When we think about risks rationally- instead of letting our perceptions be shaped and molded by emotive responses to vivid images of particular kinds of risk- it makes best sense to focus on the most probable and severe harms. Furthermore, when thinking about possible solutions to these risks of harm we should consider the costs and likelihood that we can actually do something to mitigate these harms.

Putting all this together... the biggest mistake a society could make is to ignore the most certain and severe harms that could have been most likely mitigated for little cost.

Thus the following four issues are vital:

1. The certainty of the harm (e.g. 0.1% vs 70% chance)
2. The severity of the harm (e.g. broken leg vs death)
3. The likelihood of mitigating the harm (e.g. 0.1% vs 70%)
4. The cost of mitigating the harm ($1 billion vs $1 trillion)

To make serious headway in getting people to “worry about aging” we thus need to highlight all four of these issues.

Firstly, we know that senescence causes death and disease. The scientific consensus is in. So the risks of aging are very high (and eventually become a certainty of harm for most people on the planet).

The harms of aging are also very severe. Aging increases one’s risk of disease and death. So the empirical evidence clearly shows that aging scores very high on (1) and (2). These facts alone show that aging is a BIG problem.

How about issues (3) and (4)? People are most likely to (mistakenly) assume aging research scores low on both these fronts. That is, people are skeptical that we can actually modify the biological processes of aging. But there are countless experiments in a variety of organisms that show aging is not immutable. And so the goal of retarding human aging scores reasonably well on (3). And once you add considerations (1) and (2) into the mix, it becomes evident that the current neglect of aging research is unjustified.

People will also falsely assume that (4) will require vast amounts of money. But here one must put things in their proper context. A lot of money compared to what? What we spend on national defence? National defense spending in the U.S. has reached approximately $1,600 per capita, compared to $97 per capita for federal spending on biomedical research (source)

But then the story gets even more dire when we consider how much of the funding invested in biomedical research goes towards the science that could actually make serious headway against the diseases of aging- aging research. In the year 2006, the National Institutes of Health was funded at $28 billion and yet less than 0.1% of that funding was spent on understanding the biology of aging (source).

Should we increase that spending? Yes! By how much? Well, now that is an intelligent and important conversation for us to have. The answer depends on the findings of (1), (2) and (3). Contrary to what many people think, slowing aging might be as simple as taking a “a longevity pill” that mimics the effects of calorie restriction. Taking this daily vitamin could delay all the diseases of aging and increase the number of healthy years humans all around the globe could expect to live. In fact numerous clinical trials involving an anti-aging molecule are already taking place in humans right now! So this is the science of today, not a 100 years from now.

If a longevity pill could be developed, these benefits could be enjoyed by all future generations. Generations that would be spared from the ravages of the diseases of aging. Hence why I think we really need to “worry about aging”.

Cheers,
Colin

Friday, June 15, 2012

How to Put Aging and Biogerontology in the "Justice" Spotlight



Over the past decade I have worked at the intersection of issues in political philosophy/theory and the medical sciences. I have tried to help bridge what I take to be a troublesome divide between the field most concerned with ideals of justice and equality, and scientific advances (especially in the field of biogerontology) which could profoundly improve human health and prosperity. These two things are linked in important ways, but there is very little actually written by theorists on these kinds of topics.

Bridging this gap is an up-hill struggle for a variety of reasons. The theoretical concepts and normative theories developed in political philosophy over the past 4 decades either ignored the realities of morbidity (e.g. like the fact that aging is a major risk factor for disease) or just assumed people went through their complete lives as "healthy and productive members of society". This meant the (almost exclusive) focus of theories of distributive justice was on the distribution of wealth and income. A fair society could be measured, so went the reasoning, to a large extent by the pattern of the distribution of a society's wealth. And the extent to which theories of justice have expanded, in the last 2 decades, to tackle topics like global justice and health, they are still constrained by the original assumptions and limited perspectives/concepts with which the dominant normative theories were originally devised. In other words, taking a theory of domestic justice designed to apply to a healthy and affluent society and then trying to make a few modifications once you take disease and debt seriously is not, imho, a recipe for success (though much more would have to be said about what constitutes "success" for a theory of justice).

Rawls's method of "reflective equilibrium" prioritized the importance of our "moral intuitions" about justice, something which has further marginalized the importance of well-ordered science to debates concerned with justice and good governance. We come hardwired with intuitions about the distribution of food and importance of social status, but a host of cognitive biases and limitations impair our ability to think sagely about issues that go beyond our primal moral instincts. Such instincts are unlikely to help us navigate the complex challenges facing today's aging world.

This has created an enormous challenge for me as a scholar, as I have been working on a book-length project for over a decade now on the social and ethical implications of the genetic revolution and have struggled to find an adequate normative framework which will do justice to the complexity of issues that arise in this context. When I first started working on these issues I envisioned taking a "top down" approach, by which I mean I had a normative theory in mind (broadly Rawlsian), and envisioned extending and applying that theory to advances in the biomedical sciences. And 3 years into the book I had a near complete draft of this project completed. But as time went on, and I learned more about the empirical realities of human biology (especially aging) and the advances in the biomedical sciences, I came to appreciate how impoverished my initial approach was. If the goal of a normative theory is to help us diagnosis the problems and challenges we have in the real world, both today and in the near future, a "top down" approach will be of little help. And I didn't want to write a book that would be of little to no use.

So instead I have opted for a "bottom up" approach. I began to pay closer attention to the empirical discoveries being made, and the potential interventions these discoveries could lead to, and then began to fashion and develop a normative theoretical framework from this. This "bottom-up" approach certainly requires a great deal more empirical work, patience and interdisciplinary competence, but I believe the payoff will be worth it as one's contribution will better exemplify the intellectual virtues (e.g. attention to details, understanding, etc.) than a contribution misinformed or aloof to the subject matter in question.

Those who have followed my posts over the past 5 years will know that aging and biogerontology have been a central focus of my research for the past few years. But one would find very few (there are some) papers written by philosophers and theorists which address the justice issues raised by aging populations. But global aging is among one of the greatest challenges facing developed and developing countries this century. And if political philosophers/theorists hope to develop theories and principles which take the realities of today's world seriously we must begin to take these considerations seriously.

Before turning to the main point I wish to make in this post, it is worth pointing out that the case for tackling aging and prioritizing the study of the biology of aging is easy to make from a utilitarian perspective. Utilitarianism maintains that we should maximize the greatest happiness of the greatest number. When we adopt the lens of minimizing pain and suffering in today's aging world it is very easy to see why the science of aging ought to be a top priority. I have emphasized this point in various other papers and posts so I won't re-hash that point here.

Utilitarianism has of course fallen on hard times in the past 40 years in ethics and political philosophy (at least in academia). And so much more elaborate theories and principles have been derived that make the commonsensical aspiration of aspiring to stave off the chronic diseases of late life much less obviously a moral requirement or duty of justice. Consider, for example, infectious disease and poverty. These of course have been a reality for human populations for all of our species' existence. Humans living in a "state of nature" died from communicable diseases, malnourishment, etc. This unfortunate state of affairs does not have to be construed as "human-made" before our moral sensibilities kick in. And yet today many professional philosophers have constructed elaborate theories and debates which aspire to reveal the insight that poverty and disease are the result of global capitalism and thus ought, as a matter of justice, to be redressed.

When what we might call the human-agency thesis [injustice = human actions which adversely affect the welfare of others] drives our normative theories it can pervert our moral sensibilities as well as distort our understanding of human history. And so there is something valuable to be gained by utilitarianism's simplicity. But alas I digress as the task today is to link aging with the human-agency view of justice. So let us return to that task.

Most theories of justice today focus on inequalities, disadvantages, etc. that are created by our social institutions. Feminists, for example, focus on role of the family and law in creating and perpetuating patriarchy. Egalitarians focus on the vulnerabilities and inequalities of capitalism. Libertarians might focus on the inefficiencies of government and what they take to be the potential "tyranny of the masses" of democratic government. The focus on the responsibility social institutions play in creating and promoting undesirable state-of-affairs stems from a commitment to the "human-agency" view of justice. This assumption is central to social contract theories of justice, for example, because the focus is on the terms of agreement that would be acceptable to all if all were equal participants in the social contract.

This author, for example, argues that the ordinary meaning of the word "justice" is associated with the morally appropriate, and, in particular, equitable treatment of persons and groups. As such justice is a concept utilized to assess social institutions, "a social system's practices or "rules of the game"" (37).

Claims to justice thus arise, according to the human-agency view, because human action has resulted in outcomes (e.g. patriarchy, inequality, inefficiency, poverty) that ought not to have occurred. Once social institutions are implicated in this fashion, a theory of justice will aspire to derive appropriate principles that provide guidance to help redress the shortcomings of the status-quo.

Is there a way to tell the story about the aging of the human species that resonates with the human-agency view of justice? I believe there is. And part of the difficulty in trying to expand the frontiers of justice to include modulating the rate of aging is that most people (mistakenly) assume that aging is "natural". That humans age today like they always did. And if humans aged in "the state of nature" like they do today then there is no "injustice" that needs the redressed.

Pointing out the mistakes in this assumption could thus be of some real value. Far from aging being "natural", it is actually very "unnatural", and a product of human intervention. This will no doubt strike many as counterintuitive, but this insight becomes evident once we adopt the lens of comparative biology.

Before I explain how aging is a product of human intervention, I first want to emphasize what my claim is NOT. I am not suggesting, as some do, that the problems of aging (e.g. diabetes, cancer, etc.) are created by our fat diet, inactive lifestyles, etc. While it is true that diet and lifestyle can help delay or accelerate the onset of morbidity, these are not the factors that *cause* aging. So then in what sense are humans responsible for aging?

Look around nature at, for example, wild mice, birds, and fish. Do we find the populations of these species aging? No. The birds you find sitting in the trees in your backyard, the field mice living in your garden shed, they are healthy and vigorous. In the wild they do not age because as soon as their health or agility begins decline they soon become dinner for one of their many and hungry predators. As Hayflick argues, aging is actually an artefact of civilization. Because we have, thanks to sanitation, antibiotics, increases in material prosperity, etc., significantly reduced early and mid-life mortality, we have created a very artificial environment for living things, not only for us humans, but also for our pets and other domesticated animals we protect.

So we can tell the story of aging and chronic disease as a story which implicates the human-agency premise: We have created environments that are so effective at mitigating the external threats to life for humans that our populations now experience aging. This would not occur naturally, in the "state of nature". Population aging is a product of human artifice. Aging is of course an unintended consequence of civilization. We did not create sanitation, more efficient crop production, modern medicine, etc. so that we could age. These interventions have helped postpone disease and death for today's populations. However, a consequence of these interventions is that the chronic diseases of late-life, which are often slow, expensive and painful ways to die, afflict unprecedented numbers of human beings. More human beings die year after year from chronic disease than from any other cause. And there is a duty of justice to do what we can to mitigate this tragic state of affairs.

By drawing attention to the fact that aging is a product of human action one can invoke the human agency thesis to help buttress the case for tackling the inborn aging process. It is shortsighted and arbitrary to limit the demands of justice to reducing early and mid-life morbidity and mortality. The interests children and young adults have in remaining healthy and vigorous does not decline as they enter the post-reproductive period of life. Justice requires us to prioritize the science which could significantly improve the health prospects of today's aging populations.

Cheers,
Colin