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!


"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?


(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.


"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.