Friday, December 28, 2012

Reader's Digest Interview on Aging and Longevity Science

One of the major obstacles the field of biogerontology faces is the public's perception of the importance of an applied gerontological intervention.

Having a rational and informed discussion about the pros and cons of life extension is difficult to have in the media where sound bites and exaggerated claims tend to rule the day. So scientists who work on aging face a difficult task that scientists who work on specific diseases, like cancer, stroke or AD, do not face. And I think it is unfair to expect biogerontologists themselves to take on the sole responsibility of communicating the significance of the biology of aging to the general public and policy experts. Scholars in the humanities and social sciences must also engage with these issues. And so I sometimes do offer my 2 cents worth when asked for it (and sometimes when it is not asked for :).

A few months ago I was interviewed for a piece on aging and longevity science for the January 2013 issue of The Reader's Digest (Canadian edition). I was emailed a list of set questions, and my full responses are noted below.

The magazine article only quotes two sentences from the full interview ("sound bites"), so I thought I would post the full interview here to provide a more accurate picture of my views on this topic.

Question: What are the latest and most important trends/developments/discoveries in longevity research?

Answer: The field of research known as biogerontology, which studies the biology of aging, is a truly fascinating, though often misunderstood, area of scientific research. In 2011 the gnome of the naked-mole rat was sequenced. This rodent is only the size of a mouse, and one might wonder what the significance of sequencing its genome could possibly be. But the naked-mole rate is the longest living rodent, it has a maximum lifespan exceeding 30 years and an exceptional resistance to cancer. Understanding the biology of this species could help unlock the mystery of healthy aging. A variety of experiments on fruit flies, mice and other species have demonstrated that the rate of aging can be manipulated, either by calorie restriction or by activating particular genes. Such research could eventually lead to the development of a drug that safely mimics the effects of caloric restriction (which delays the onset of disease) or actives the “longevity genes” that help protect against the diseases of late life.

Question: How can positive biology help us find the key to longevity?

Answer: The lion’s share of funding for medical research is spent on disease research, such as research on cancer, heart disease or Alzheimer’s disease. This approach, which I call “negative biology”, assumes that the most important question to answer is “what causes disease?”. Unfortunately this is a severely limited approach, especially for older populations. Even if you cured all 200+ forms of cancer (and we have not yet eliminated even just one cancer despite investing enormous sums of money for decades now), one of the other diseases of aging would quickly replace cancer as the leading cause of death because most people in late life are vulnerable to multiple diseases. So “positive biology” takes a different intellectual starting point. It assumes that the puzzles of exemplar health are just as important to understand as the development of disease. How can some (very rare) humans live over a century of disease-free life? Understanding these exemplar examples of health might prove to be more significant than trying to understand, treat and cure every specific disease of late life.

Question: Do you think a life extension pill is possible? If so, when do you foresee something like this becoming available?

Answer: Yes, I believe a safe and effective intervention in the aging process will be developed. It would, at a minimum, delay the onset of disease and frailty, but it might also compress the period of time people live with severe disability, suffering and disease. So the goal is to increase the number of healthy years people can have, not extend the period of time we are alive by managing multiple diseases, which is the current route negative biology is taking us down. It is very difficult to estimate the timeline for an aging intervention. Much depends on the amount of funding and resources we devote to the basic science of aging. With sufficient support I believe it is safe to assume that the children alive today will age differently than their grandparents are currently aging. That is a conservative prediction, something may be developed in time to also benefit the parents and grandparents of today. But that is less likely to happen unless biogerontology is made a much greater societal priority than it currently is.

Question: To what extent is aging and dying a psychological process versus a biological process?

Answer: That is an interesting question, and of course our psychology is a biological process as well. As we advance with age and acquire more experience and an appreciation for how finite the time we have alive is, this alters our priorities for life. There is a growing literature on the science of happiness which shows that happiness increases at older ages. So the story of aging is not just about how our risks of disease, frailty and death increase over time, it is also a story about how adaptive the human mind and spirit can be. And that part of the story is a positive one.

Question: When it comes to longevity, what role do genes versus lifestyle play?

Answer: The scientific evidence on this issue is very clear, but it is easy get confused or be misled about the issues. It really depends on whether one is talking about the average person, who has a maximum lifespan of around 85 years, or those rare individuals who can live 100+ years. For the most of us, lifestyle is extremely important in terms of determining our risk of disease in late life. Smoking, poor diet, and inactivity dramatically increase the chances we will have a premature death from cancer, heart disease or stroke. However, even ideal lifestyle would not result in people living to 100 years. The story of the determinants of exceptional longevity is one of genetics rather than lifestyle. The rare individuals that can survive beyond a century of life are not former Olympic athletes, or vegetarians or those that only eat organic food or practice yoga daily. What these individuals do share are protective “longevity genes”, which run in their families. That is why it is so important to learn about the biology of people who age in this exceptional manner, so that we could design drugs to mimic their biology so everyone has the opportunity to enjoy more health in late life.

Question: Why do you think humans are obsessed with extending their time on earth?

Answer: I think what humans are obsessed with is staying healthy and alive, rather than extending their time on earth. Everyone would like to wake up tomorrow morning alive and healthy. If we did not have this survival instinct our species would have died off long ago. And the world is an adventurous place, and our time here is very limited. So I think it is natural that we aspire to have more time to experience all that life has to offer.

Question: Some argue that immortality might be a feasible goal in the future (see Immortality Project 2045 at ), what is you view on the prospect of humans achieving immortality?"

Answer: While I think it is likely that the aging process will be slowed in the foreseeable future, this does not mean humans will become immortal. It just means we could reduce the prevalence of the diseases of aging compared to what they would be under the current rate of aging. People would still die from disease, not to mention car accidents, homicide, suicide, etc. I do not believe the science supports talk of “immortality”, that is more science fiction than science.

Question: What are the five most important lifestyle choices a person can make if they want to live to 100?

Answer: Well, I’m afraid no lifestyle choice will guarantee people make it to their 100th birthday (you need the “longevity genes” for that!). Nonetheless, one can adopt certain habits of body and mind which will help ensure people have more health and happiness in the time they have. So my list would be:
1. Live an active and social life.
2. Appreciate and treasure the joys of your life, like time with loved ones, walks in nature, and hobbies that interest you.
3. Try not to fixate on the little things in life that irritate or frustrate you or the things you cannot control.
4. Be sure to frequently reflect upon the achievements you are most proud of in your life, such as your contributions to your family, community, country and humankind.
5. The one lifestyle choice people can make which could increase the odds of their making it to a 100 would be to support the scientific study of aging and longevity!

Question: You say that those who make it past 100 have special longevity genes. How does this idea coincide with the stat showing 25-40 percent of our longevity is predetermined?

Answer: Part of the difficulty with making estimates about the precise % to be attributed to genes and extrinsic factors we can control (like lifestyle) is that it really depends on whether one is talking about the average (maximal) lifespan for humans, or the maximum lifespan (which is at least 122 years). And it also depends on what we take the background extrinsic factors to be. For example, if there is no food available for humans to eat, then their longevity will be nil. In that sense, extrinsic factors determine lifespan by 100%. But the stat you mention is one generated against a certain background of extrinsic risks, those typical of a developed country like the United States.

Most people do not possess the genetic determinants required to reach the exceptional longevity of 100+ years. Of course the average person does possess the genes needed to live beyond 60 years of age, provided they are protected from extrinsic risks like infectious disease, poverty, etc. And how things play out for these people in the 6th, 7th and 8th decade of life is significantly influenced by extrinsic factors (e.g. did they smoke, exercise, etc.). So the story of the role of lifestyle in longevity is much larger when considering average people who are unlikely to die very young (because they do not have the (rare) genes implicated in early onset disorders) or live exceptionally long lives (because they don't have the "longevity genes").

But for the outlier cases- very short lives (caused by genetic disorders) and very long lives- genes have a much greater influence. If you are born with the genetic mutation for infantile Tay-Sachs disease, for example, you are unlikely to live past early childhood. So for is group of people their genes play a much greater role in limiting their lifespan. And the story is similar for those at the other end of the spectrum. For the longest lived their genes play a greater role in longevity than for the average person. And because such individuals are rare, it means that genes play, in the larger picture of things, a smaller role in human longevity when we consider the overall picture of things for average people.