Friday, October 30, 2009

Nature Editorial on Gene Therapy


The latest issue of Nature has this insightful, and refreshing, editorial on renewing our optimism for gene therapy. Here is a sample:

In the early 1990s, when the first human trials got under way, it seemed to many that the era of gene therapy was at hand: the techniques of modern molecular biotechnology would make it possible to repair genetic defects by inserting healthy DNA directly into a patient's cells. The excitement was short-lived. Lasting effects proved difficult to obtain in early trials, and the community quickly grew sceptical. Then, in 2003, when it was announced that several gene-therapy patients in a Paris-based clinical trial had developed leukaemia, and that one of them had died, the mood became bleak. Subsequent reports of successful and effective gene-therapy trials have done little to lift the prevailing sense of doom. For most researchers, gene therapy now seems like a dead end.

....To reverse this trend, it is time for researchers and industry to refresh their perspective on gene therapy and to consider its successes with as much intensity as its setbacks. The focus on adverse events has had positive consequences: researchers dissected the exact molecular mechanisms that led to cancer, designed better vectors, devised animal models to test these vectors and developed sophisticated assays for monitoring patients. As a result, both scientists and clinicians now have a battery of extraordinarily refined tools for preclinical and clinical studies of gene therapy. The field is ripe for further successes.

Cheers,
Colin

Thursday, October 29, 2009

21st Century Humanism


As a humanist I believe in the equal worth of all human beings. My humanist sentiments open my eyes to the problem of global poverty, the pervasiveness of patriarchy and the dangers of extremism.

My humanist sentiments also open my eyes to the shortcomings of evolution (evident by the prevalence of chronic disease in late life) and the prevalence of "ageism". In this post I will address these latter concerns.

If humanists reflected critically and consistently upon their basic moral convictions, I believe they would become strong advocates of aging research and the aspiration to decelerate human aging. However, most humanists are not (at least yet) strong advocates of this scientific research; indeed many probably oppose this research or at the least do not think it an important priority. In this post I will explain why this is a mistake given the foundational moral premises of humanism.

What separates me from those humanists who ignore or eschew aging research is that I am a 21st century humanist, while they are 20th century humanists. A 21st century humanist endorses the aspirations of 20th century humanists (e.g. racial equality, the elimination of gender, the elimination of world poverty, etc.), but we go one step further by incorporating the challenges of an aging world and the rapid advances in biomedical science into our purview of the demands of justice (see this excellent article which played a major role in bringing me around to thinking more rationally about these issues).

A 21st century humanist recognizes the fact that no person, regardless of race, gender, nationality or *age*, deserves to suffer morbidity and mortality. And thus we ought to aspire to reduce these risks when it is feasible to do so, whether it be by providing access to clear drinking water, bed nets to protect against malaria or developing new drugs that re-programme our metabolism and help protect against chronic diseases.

For the first time in human history, most disease and death this century will occur in late life. Aging will cause hundreds of millions of cancer deaths, strokes, bone fractures, infections, etc. Furthermore, these chronic diseases are extremely costly. The Centre for Disease control estimates that chronic diseases account for 70% of all deaths in the United States and the medical care for people with chronic diseases account for more than 75% of the nation’s $2 trillion medical care costs. (source)

20th century humanists seek to mitigate socially created harm and oppression, whereas 21st century humanism extends the concern for the equal worth of all beyond the harms created by social institutions. 21st century humanism also seeks to mitigate the adverse consequences of natural selection- in particular, the evolutionary neglect that leaves humans vulnerable to late-life morbidity and mortality.

The average age of life expectancy, at birth, in the world today is 67. This means that most people born today will live long enough to suffer one of the chronic diseases of aging, like cancer or heart disease. This is a fate suffered by millions every year now, especially in the developing world (contrary to what most people in the developed world think).

21st humanists ought to be among the strongest and loudest advocates of biogerontology. For the goal of "healthy aging" is one that follows from the core humanist sentiment that the worth of all human life, regardless of chronological age, is equal. Once humanists open their eyes to the reality of today's aging world, appreciate the incredible advances that are being made in the biomedical sciences, and discard their ageism, perhaps they will embrace a public philosophy well suited for meeting the full range of challenges we face in the "here and now" (and in the years to come).

Cheers,
Colin

Friday, October 23, 2009

Biogerontology Paper on Framing the Inborn Aging Process
















My paper entitled "Framing the Inborn Aging Process and Longevity Science" has been accepted for publication in the journal Biogerontology.

This paper integrates insights from economics, psychology, evolutionary biology, demography, and epidemiology in an effort to help equip us for tackling this century's greatest challenge-- the rapid rise of chronic disease that accompanies population aging.

This paper is probably my most ambitious paper to date, and was a real labour of love. Here is the abstract:

The medical sciences are currently dominated by the “disease-model” approach to health extension, an approach that prioritizes the study of pathological mechanisms with the goal of discovering treatment modalities for specific diseases. This approach has marginalized research on the aging process itself, research that could lead to an intervention that retards aging, thus conferring health dividends that would far exceed what could be expected by eliminating any specific disease of aging. This paper offers a diagnosis of how this sub-optimal approach to health extension arose and some general prescriptions concerning how progress could be made in terms of adopting a more rational approach to health extension. Drawing on empirical findings from psychology and economics, “prospect theory” is applied to the challenges of “framing” the inborn aging process given the cognitive capacities of real (rather than rational) decision-makers under conditions of risk and uncertainty. Prospect theory reveals that preferences are in fact dependent on whether particular outcomes of a choice are regarded as “a loss” or “a gain”, relative to a reference point (or “aspiration level for survival”). And this has significant consequences for the way biogerontologists ought to characterise the central aspirations of the field (i.e. to prevent disease versus extend lifespan). Furthermore, it reveals the importance of shifting the existing reference point of the medical sciences to one that is shaped by the findings of evolutionary biology and biodemography.

Cheers,
Colin

Wednesday, October 21, 2009

Cancer Funding in Canada

Today's Globe has this interesting piece on how small the portion of cancer research spent on childhood illness is. A sample:

One dollar in every $30 invested in cancer research goes specifically to research on childhood and adolescent cancers, according to a new report.

In 2007, $13.2-million of the $402.4-million that was invested in cancer research in Canada was aimed at understanding the causes and improving the cancer of younger patients, the study from the Canadian Cancer Research Alliance shows

Now the fact that only 3% of cancer research focuses on childhood illnesses will surprise, and no doubt trouble, many people.


Let me first address the sensibility that spending only 3% of cancer funding on childhood and adolescent cancers is unfair. What most people don't realise is the fact that cancer is predominately a disease of aging. Like other chronic diseases (heart disease, AD, etc.), most people who die of cancer are over the age of 65. So if one wants to spend money on things that will help save more young lives then one should support tackling more prevalent risks. Look here, for example, to see what kills more young people than cancer. For every young person ages 14-24 that dies of cancer, 6 die in accidents, and 3 die from suicide.

Furthermore, the death rates for the young in Canada are very low, especially compared to the morbidity and mortality rates of the aged. This is not to suggest that we shouldn't do more to reduce early life morbidity and mortality (we should), but that any response should be proportionate to the risk. A 20 year-old smoker has a much lower risk of cancer and death than a 75 year-old active, non-smoker. Why? Because aging is the major risk factor for disease and death in Canada.

So while the intuition that it is unfair to spend so much on cancer research for the aged rather than the young misses the mark, there is a legitimate complaint to make here. Once we make explicit the point that cancer research aims, primarily, at benefiting people in late life, how much bang for the buck will it actually yield? Would we be better served investing more money in aging research rather than cancer research?

Imagine, as fantastical as it is, there was no cancer in Canada. That all 200+ types of cancer were eliminated overnight, just like that. How much longer could Canadians expect to live? 10 years? 20 years? 40 years? The answer will no doubt surprise you. If there were no cancer to kill us the *average* life expectancy would rise by about 3 years.

Why is the number so low? Because removing cancer as a cause of death will simply delay, by only a few years for most people, one of the other chronic diseases of aging. So a 75 year-old who doesn't die of cancer will probably suffer a stroke or heart attack a few years later. See this paper in Science for an overview of the estimates of the upper limits of human longevity.

Aging limits average life expectancy to around 85 years. To add real quality of life in late life we need to tackle the major cause of chronic diseases--- aging itself.

So the real problem with the current approach is that by aggressively going after each specific disease of aging, rather than the aging process itself, we pursue a sub-optimal approach to health extension. One that requires much more funding and yields smaller health dividends. Retarding aging would help delay, simultaneously, most these afflictions, thus freeing up more money to spend on improving the lives of young Canadians.

Thus everyone, young and old alike, would benefit from a more inclusive approach to medicine. To get there we need doctors and medical researchers (and politicians and the general public!) to adopt a Darwinian-based approach to health and disease.

The funding numbers for cancer research reveal that cancer research is really striving to help the aged. But the problem is it focuses only on the proximate cause, rather than the ultimate cause, of mortality. If you really want to improve the health prospects of people in late life we should search for ways to modulate the biological clocks we have inherited from our Darwinian past.

Cheers,
Colin

Monday, October 19, 2009

Surfing Web Good for Older Brain













This EurekAlert! notes a recent study that found that middle-aged and older adults with little Internet experience were able to trigger key centers in the brain after just one week of surfing the Web. A sample:

The findings, presented Oct. 19 at the 2009 meeting of the Society for Neuroscience, suggest that Internet training can stimulate neural activation patterns and could potentially enhance brain function and cognition in older adults.

As the brain ages, a number of structural and functional changes occur, including atrophy, reductions in cell activity and increases in deposits of amyloid plaques and tau tangles, which can impact cognitive function.

Research has shown that mental stimulation similar to that which occurs in individuals who frequently use the Internet may affect the efficiency of cognitive processing and alter the way the brain encodes new information.

"We found that for older people with minimal experience, performing Internet searches for even a relatively short period of time can change brain activity patterns and enhance function," said study author Dr. Gary Small, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and the author of "iBrain," a book that describes the impact of new technology on the brain and behavior.



Cheers,
Colin

Sunday, October 18, 2009

Nature News Feature on Cognitive Enhancement


The latest issue of Nature has this interesting "News Feature" story on the current state of neuroscience and the goal of enhanced cognition. Here is a sample:

Researchers have now created or identified at least 33 mutant mouse strains that, like Doogie, have enhanced cognitive abilities. The animals tend to learn faster, remember events longer and solve complex mazes better than ordinary mice. And because the molecular pathways used in the brain to form long-term memories are almost identical in humans and rodents, the hope is that the work will inform research into treatments for a wide variety of learning and memory problems, from dyslexia to dementia.

Much of the work involves making an adult brain behave more like a younger, more flexible version of itself by increasing the organ's plasticity. This, in turn, means that some problems, long believed to have been made permanent during development, might actually be reversed.

....Many scientists are concerned that the animal models of enhanced cognition might obscure subtle side effects, which can't be studied in rodents or primates. Farah is currently looking at the trade-off between enhanced attention — she gives human subjects a mild amphetamine — and performance on creative tasks. Other researchers have used computer models to show that memory is actually optimized by slight imperfections, as they allow one to see connections between different but related events9. "The brain seems to have made a compromise in that having a more accurate memory interferes with the ability to generalize," Farah says. "You need a little noise in order to be able to think abstractly, to get beyond the concrete and literal."

....Although Silva recognizes the risks of enhancement, he remains hopeful that the performance of the normal human brain can be improved by neuroscience. "We're getting to a point where we almost need these enhancements," he says. "We don't have enough attention, we don't have enough memory, we don't have enough awake hours. There's clearly a demand to optimize the human brain given what it needs to do in the information age."

Cheers,
Colin

Saturday, October 17, 2009

Interesting Globe Article


I seldom write anything on Canadian politics on this blog, but this article in today's Globe is very insightful and explains why, if I were a betting man, I would wager that there will be a Conservative majority government in Canada this time next year (unless the Liberals can come up some truly helpful and creative ideas and do so quickly, which I think is unlikely).

It all feels like a case of déjà vu.

The simplistic lesson to be learned from all this?

The combination of
(1) Liberty Party = Green Party
AND
(2) Conservative Party = Old Liberal Party
RESULTS IN
(3) Conservative Party = Governing Party.


Can the Liberals come up with some new ideas to give the Conservatives a real run for their money? Only time will tell.

Cheers,
Colin

Friday, October 16, 2009

Chronic Disease in the United States (and the World)



When media headlines are dominated by the economy, global warming and terrorism, it is imperative that we step back from "the hype" and turn to actual data to reveal what really are the greatest challenges we face.

This chart from the Centers For Disease Control and Prevention ought to make the headlines of the evening news every single evening (since it doesn't, it headlines this blog for tonight!).

Reporting on reality is not entertaining, hence why little attention is paid to chronic disease. But this blog does not aspire to entertain (which no doubt severely limits its readership! :)). So I will provide us with "the facts". And hopefully this will stimulate new insights to help us get serious about today's challenges.

Consider this-- in the year 2005 the total deaths caused by the three leading causes of death in the United States (heart disease, cancer and stroke) far outnumber the complete category of "unintentional deaths". For every person who dies in a car crash, plane crash or workplace accident, etc., 100 people die from one of these three chronic diseases. The next time you see a media story about a hiker who died in a remote mountain, or a person being malled by a tiger at a zoo, just bear in mind how many more deaths occur from chronic disease every single day and go unreported.

Furthermore, and it is imperative that we recognise this, most chronic diseases afflict the aged.

So most of the people who died from heart disease, cancer or stroke were over the age of 65. More than three quarters of cancer deaths (76%) occur in people aged 65 years and over (source). According to the American Heart Association, over 83 percent of Americans who die of coronary heart disease are age 65 or older (source).

Aging causes most disease and death and yet we spend a minute fraction of public funds studying the biological processes of aging compared to the vast amounts spent on national defence and trying to control the climate and the economy. Gaining some control over the biological clocks we have inherited from our evolutionary past would yield enormous health and economic dividends. Age retardation might prove to be one of the most optimal ways to prevent chronic disease. Yet the social and political obstacles that impede this vision of preventative medicine are perhaps even bigger obstacles than the scientific ones aging researchers face.

One last point. Many of you are probably thinking "yeah, yeah, aging and chronic disease are problems in rich America. But what about the rest of the world? Surely infectious diseases like HIV and malaria and poverty kill more people than chronic disease". Well, if you are inclined to think that you should think again. Yes, HIV, malaria and poverty are very serious problems in poorer countries. But chronic diseases kill far more people. In lower middle income countries like China and India the World Health Organization estimates that chronic diseases are estimated to account for 75% of all deaths over the coming decade (source). And chronic diseases are on the rise in the poorest countries in the world (see here).

The 21st century is set to be the century of chronic disease. To meet the challenges of chronic disease we need to understand the ultimate (or evolutionary) and not just proximate causes, of these diseases. Hence why aging research should be among our top priorities for a new global health initiative. One with more health, less disease, disability and suffering, and greater economic prosperity for all. That's a world worth fighting for! To achieve it we must overcome the vulnerabilities of evolutionary neglect.

Cheers,
Colin

Wednesday, October 14, 2009

New Journal: Translational Medicine


Science has just launched a new exciting journal entitled Translational Medicine. See the details here.

The latest issue of Science has this insightful editorial about the journal by Bruce Alberts. Here is a sample:

Knowledge accumulates as science advances, and science and technology are generating new knowledge at an increasing pace. The acceleration becomes understandable once one recognizes that new knowledge is formed by creatively combining old knowledge in new ways, and that, for example, 100 pieces of knowledge can be combined in 100 times more ways than can 10 pieces of knowledge. The most striking innovations often come from combining knowledge across disparate domains, but only a tiny fraction of such combinations will be useful, making research strategies ever more critical as science proceeds. Great science therefore resembles great art in the sense that an outstanding scientist has carefully selected a "subject" (the unsolved problem to attack) and the "brushes and paints" (the research strategy and techniques), using them to skillfully create a pleasing original "painting" (a new explanation of some aspect of the natural world).

The opportunities and the challenges in translational medicine are enormous, and constant waves of innovation will be needed to meet them. New ideas and approaches are essential. Too often, information with the potential to improve human quality of life is available only through silo-like channels. For example, cardiologists who only attend specialized meetings and read the cardiology literature, but not the physics or computer science literature, can miss an important breakthrough that could advance their own research. To stimulate innovation, we must intentionally catalyze the mixing of scientists and clinicians from different disciplines, knowing that new approaches will emerge from their interactions. Science Translational Medicine strives to increase such mixing by keeping researchers informed about relevant advances across all disciplines.

And the video below details the how journal aspires to translate the incredible advances being made in our understanding of biology into benefits for human health. Such an aspiration is vital if we are to meet the challenges we face today in the 21st century.



Cheers,
Colin

Tuesday, October 13, 2009

Is Retirement Actually Bad for Your Health?


...this interesting study in the latest issue of Journal of Occupational Health Psychology suggests that it might be, at least when compared to the retiree health outcomes of those who take on "bridge employment". Here is the abstract:

The present study examined the relationship between bridge employment and retirees’ health outcomes (i.e., major diseases, functional limitations, and mental health). We used a nationally representative sample of 12,189 retirees from the first 4 waves of the Health and Retirement Study. Hierarchical regression analyses showed that compared with full retirement, engaging in bridge employment either in a career field or in a different field was associated with fewer major diseases and functional limitations, whereas engaging in career bridge employment was associated with better mental health. The findings highlight the health benefits of engaging in bridge employment for retirees. The practical implications of this study are discussed at both the individual and policy levels. Limitations of the current findings are also noted in conjunction with future research directions.


Cheers,
Colin

Cell PaperFlick Video on Lifespan Extension



The latest issue of Cell has this paper which examines the mechanism involved with lifespan extension via dietary restriction. The video above (Cell's PaperFlick file) summarizes the paper's findings and here is the abstract:

Dietary restriction (DR) extends lifespan in multiple species. To examine the mechanisms of lifespan extension upon DR, we assayed genome-wide translational changes in Drosophila. A number of nuclear encoded mitochondrial genes, including those in Complex I and IV of the electron transport chain, showed increased ribosomal loading and enhanced overall activity upon DR. We found that various mitochondrial genes possessed shorter and less structured 5′UTRs, which were important for their enhanced mRNA translation. The translational repressor 4E-BP, the eukaryotic translation initiation factor 4E binding protein, was upregulated upon DR and mediated DR dependent changes in mitochondrial activity and lifespan extension. Inhibition of individual mitochondrial subunits from Complex I and IV diminished the lifespan extension obtained upon DR, reflecting the importance of enhanced mitochondrial function during DR. Our results imply that translational regulation of nuclear-encoded mitochondrial gene expression by 4E-BP plays an important role in lifespan extension upon DR.For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.


Cheers,
Colin

Friday, October 09, 2009

NEJM Review on Aging and Cancer


The latest issue of the New England Journal of Medicine has this interesting review article on aging and cancer. Here is a sample:

DNA damage has emerged as a major culprit in cancer and many diseases related to aging. The stability of the genome is supported by an intricate machinery of repair, damage tolerance, and checkpoint pathways that counteracts DNA damage. In addition, DNA damage and other stresses can trigger a highly conserved, anticancer, antiaging survival response that suppresses metabolism and growth and boosts defenses that maintain the integrity of the cell. Induction of the survival response may allow interventions that improve health and extend the life span. Recently, the first candidate for such interventions, rapamycin (also known as sirolimus), has been identified.1 Compromised repair systems in tumors also offer opportunities for intervention, making it possible to attack malignant cells in which maintenance of the genome has been weakened.

Time-dependent accumulation of damage in cells and organs is associated with gradual functional decline and aging.2 The molecular basis of this phenomenon is unclear,3,4,5 whereas in cancer, DNA alterations are the major culprit. In this review, I present evidence that cancer and diseases of aging are two sides of the DNA-damage problem. An examination of the importance of DNA damage and the systems of genome maintenance in relation to aging is followed by an account of the derailment of genome guardian mechanisms in cancer and of how this cancer-specific phenomenon can be exploited for treatment.

....DNA damage can trigger the development of cancer, accelerate aging, or both, depending on the type, amount, and location of the damage; the type of cell sustaining the damage and its stage in the cell cycle; and the specific repair, checkpoint, and effector systems involved. When the damage is not repaired, the outcome may be cancer or, if cell death or senescence occurs, protection from cancer, but the trade-off is acceleration of the aging process. The development of cancer and the process of aging can be delayed by reducing the load of DNA damage — by avoiding or limiting exposure to exogenous genotoxins and by suppressing metabolism — thereby producing fewer reactive species. However, DNA damage, like caloric restriction, can also elicit a protective survival response that promotes longevity and healthy aging. Recently, the use of sirolimus in mice was found to extend their life span and delay the development of conditions associated with aging, including cancer.1 Sirolimus is one of presumably many compounds that may elicit the survival response. The frequent derailment of DNA damage-response systems in tumors presents another possible route by which new treatments can act selectively on the tumor.

Cheers,
Colin

Thursday, October 08, 2009

Statins and Health Inequalities: Some Thoughts


Last week I read this article on statins and health disparities which provoked a few different thoughts which I wanted to note here, especially as they pertain to similar concerns that arise with respect to aging interventions and debates in biogerontology.

Before addressing the article let me say a bit about "egalitarianism". My understanding of the term "egalitarian", at least as that term is commonly utilized in contemporary debates in political philosophy, is that it is a term attributed to one who believes that distributional equality of some good or goods (like wealth or health) has considerable moral value in itself (and, conversely, that (unchosen) inequality is unjust).

As I have noted before, I myself am not an egalitarian. When it comes to the issue of how much weight to attribute to equality, the devil is really in the detail (not the abstract concept!). Much depends on the good in question, the level of disparity, and the causes of the inequality and the different challenges that often impede the realization of a more equal (or rather optimal) situation.

I take a diachronic, rather than synchronic, view of justice. Telling me that inequality X is present at time 1 tells me little (if anything) about the justness of a situation. But for those inclined to adopt a synrchonic view of justice, one that is premised on our abstract intuitions concerning what is fair, hearing that an inequality exists is all they need to hear before they are inclined to demand that we mitigate such inequalities (even possibly by levelling down, depending on how strict of an egalitarian one is).

Even though I am not an egalitarian, I am interested in learning why so many (at least academics) hold such a view and what follows from their position. In this earlier post, for example, I argued that if one is an egalitarian of the kind Cohen defends then one ought to take seriously the issue of how inclusive your choice of partner is (which I actually think is a tenable conclusion, but not by appeal to egalitarian concerns).

And in this post I brought attention to the fact that the infant health inequality among the rich and poor has narrowed. To an egalitarian, the information that the gap between the neonatal and infant mortality of rich and poor infants has narrowed might be cause for celebration. Less inequality is inherently good. However, once one notes the reason why this is so-- namely, that part of the reduction in infant health inequality is due to the fact that children of highly educated parents now have an increased risk of complications and death because mothers are more likely to utilise fertility treatments, and hence have a higher change of multiple births-- the intuition "less inequality is good" looks perverse. When it comes to health, "leveling down" is not the goal. What we really want is to bring everyone up. So prioritarianism, or sufficiency, probably underpins most the sensibilities of those who claim to be egalitarian.

This brings me to the article on statins and health inequalities. My interest in this article stems from my interest in the egalitarian objection to aging interventions. Many critics dismiss the prospect of an aging intervention because such a medical intervention, when it arrives (and I think it is really a question of when, not if) will not (at least immediately) be available to all people on the planet. And from this they form the judgement that, "all-things-considered", such a technology will exacerbate injustice and do more harm than good. And thus these kinds of sentiments impede the development of biogerontology, perhaps this century's most important science.

But such a judgement is very naive and misguided. In fact, one can only arrive at such a judgement if one develops a judgement of what justice requires "only-one-thing-considered"-- and that one thing is what weight ought we to place on the abstract value of equality? But if we insist on subjecting our moral sensibilities to a determination of what justice requires "many-things-considered"-- then we will not eschew medical innovations that might have some adverse (at least) short-term impact on relational considerations but, in absolute terms (and in the long run), will improve the situation of all.

It is important to recognise that health is not a zero-sum game- that is, a game where the total amount of health available is fixed and redistributed, so that extra health for X comes at the price of less health for Y. Of course in some cases, like rationing scarce medical resources, things are like this. Either we fund treatment for disease A or for disease B. But we should not generalize from these cases to health in general.

Health itself is not a zero-sum game. If you achieve more health via exercise and diet that benefit does not come at the cost of someone else who thus suffers more disease and an earlier death. Your remaining healthy for longer need not reduce the amount of health available to me. Indeed, by remaining healthy and productive you can increase the likelihood that health dividends will also come my way by helping to reduce the strains on medical resources that are scarce and need to be rationed.

This brings us then to the study on statins. Statins are cholesterol lowering drugs that can reduce the risk of cardiovascular disease. But statins are not freely available. And thus those who can afford them enjoy a reduced risk of heart disease. A sample from the paper:

As an innovation, statins have a number of attributes favoring effective diffusion and adoption. Classical diffusion theory considers the following factors: “relative advantage” (e.g., effectiveness relative to alternatives), lack of “complexity” (e.g., simplicity of use), “compatibility” (fit with existing values and practices), “observability” (outcomes can be observed), and “trialability” (users can experiment on a limited basis) (Rogers 2003). Statins possess, to some degree, all of these attributes, and each can be considered from the standpoint of both physician and patient as the adopter. Empirical data suggest that the diffusion of statins has indeed been rapid.

....Statins are far more powerful than prior cholesterol-lowering drugs and, of particular importance, are highly effective in lowering low density lipoprotein (LDL), the fraction of total cholesterol that is most closely associated with heart disease and the principal target of treatment guidelines (NCEP 2002). Statins can achieve reductions of up to 50 percent or more in LDL (Jones et al. 1998), but they are expensive. Simvastatin (brand name “Zocor”) is one of the most effective and frequently prescribed statins, and its cost was over $120 a month in 2003 for a starting dose of 20 milligrams per day (The Medical Letter 2003). In addition to being costly, statin use requires access to lab services and physicians who prioritize prevention, adhering to guidelines for cholesterol screening and treatment. It also requires resources such as patient willingness and ability to fast overnight and present for a scheduled blood draw. Blood analysis is essential for diagnosis, drug titration, and monitoring side effects.

....While the more advantaged were once more likely to have high levels of cholesterol and LDL, they are now definitively less likely. Additionally, exploratory analyses suggest that income is positively associated with statin use accounting for clinical need. While statins hold great promise for improving cardiovascular health, it appears that they may have contributed to expanding social disparities in cardiovascular risk.

....The influence of technologies on socioeconomic disparities is subject to two important modifiers: (1) the nature of the technological change and (2) the extent of its diffusion and adoption. While resources affect access to technologies, some technologies can also affect resources, lessening the productivity of various health inputs. In our case, statins could have helped to equalize cholesterol levels by overtaking the value of lifestyle inputs. Significant disparities in diffusion and adoption, however, resulted in a net effect of gradients favoring the wealthy. It is important to note that average cholesterol levels declined during this period at all income levels. Hence, statins have contributed to an overall improvement, yielding absolute health benefits at all incomes. Health enhancing innovations, however, are typically implemented in a context of inequalities, and an innovation that raises average health can nevertheless create new links between social factors and disease pathways.


So what to make of this? Well, if what one really wants to argue is that everyone, and not just the rich, should have access to statins, then we should invoke a prioritarian or sufficiency or even utilitarian framework. An egalitarian framework distracts us from the real concern (i.e. access to statins) and often leads people to endorse the conclusion "then none should have access to X". There is much more to be said here. But I will leave things there as this is a complex issue which requires more reflection that I can offer here at the moment. But I want to leave things with this final thought:

I believe the prevalence of egalitarian intuitions helps explain (at least in part) the dominance of the "disease model" approach to the medical sciences. People eschew aging research and positive psychology because they believe it is inappropriate to worry about improving the health and happiness of those they consider "the advantaged", when there are those who suffer early onset disease and mental illness. But we should reject this simple dichotomy and its conclusion that we should only use science to help those with the worst afflictions.

To overcome the exclusive vision of the medical sciences (namely, that medicine should only aid those who are sick and ill) we need to overcome these misplaced moral sensibilities. Fairness is much more complex than invoking simple egalitarian intuitions.

Cheers,
Colin

Tuesday, October 06, 2009

Inhibition of S6K1 Gene Increases Lifespan


This study in the latest issue of Science is yet another reason why aging research is among the most exciting, and important, areas of scientific research today.

Researchers from UCL, the Wellcome Trust, Imperial College, the University of Cincinnati and Aberdeen University have identified a gene, S6K1, that influences healthy mammalian life-span. Here is the abstract:

Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)–activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.


Cheers,
Colin

Monday, October 05, 2009

Noble Prize in Medicine (2009)


The noble prize in medicine has been awarded to three researchers for their discovery of telomeres, and working out how they protect chromosomes from degradation.

Naturenews has the scoop here. A sample:

Three US scientists have won the Nobel Prize in Physiology or Medicine for discovering the structure of molecular caps called telomeres and working out how they protect chromosomes from degradation. Their discoveries in cell biology during the 1980s and 1990s opened new avenues of work, in ageing and in cancer research, which are still highly active today.


And this interview explains this scientific research.

Cheers,
Colin

NY Times Piece on Slowing Aging


This story is a few weeks old but worth noting, the NY Times published this excellent piece on age retardation back in August that is well worth the read. It covers research on calorie restriction and sirtuin activating compounds. Here is a sample:

It may be the ultimate free lunch — how to reap all the advantages of a calorically restricted diet, including freedom from disease and an extended healthy life span, without eating one fewer calorie. Just take a drug that tricks the body into thinking it’s on such a diet.

It sounds too good to be true, and maybe it is. Yet such drugs are now in clinical trials. Even if they should fail, as most candidate drugs do, their development represents a new optimism among research biologists that aging is not immutable, that the body has resources that can be mobilized into resisting disease and averting the adversities of old age.

....In the view of evolutionary biologists, the life span of each species is adapted to the nature of its environment. Mice live at most a year in the wild because owls, cats and freezing to death are such frequent hazards. Mice with genes that allow longer life can rarely be favored by natural selection. Rather, the mice that leave the most progeny are those that devote resources to breeding at as early an age as possible.

According to this theory, if mice had wings and could escape their usual predators, natural selection ought to favor longer life. And indeed the maximum life span of bats is 3.5 times greater than flightless mammals of the same size, according to research by Gerald S. Wilkinson of the University of Maryland.

In this view, cells are so robust that they do not limit life span. Instead the problem, especially for longer-lived species, is to keep them under control lest they cause cancer. Cells have not blocked the evolution of extremely long life spans, like that of the bristlecone pine, which lives 5,000 years, or certain deep sea corals, whose age has been found to exceed 4,000 years.

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