Saturday, September 26, 2009

Obesity and Aging Linked

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

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

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

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

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

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

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

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

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

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

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

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

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

And here is the abstract of the study:

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

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

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

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