April 18, 2006

The Skinny on Longevity

It’s been known for some time that skinny rats live longer than fat rats. They have to be extremely svelte for this effect to kick in: laboratory rats that consume 60% of the usual rat diet live 30% longer than the average rat. Studies are underway in primates, but because monkeys live for many years, the results of “caloric restriction,” as the intervention is called, on their longevity is not yet know. But a new study in the Journal of the American Medical Association suggests that a comparable phenomenon is at work in people.

A team of researchers from Louisiana State University in Baton Rouge and the Garvan Institute for Medical Research in Darlinghurst, Australia reported on a randomized study involving 48 people (see Leonie Heilbron, Lilian de Jonge, Madlyn Frisard et al, “Effect of 6-Month Calorie Restriction in Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals,” Journal of the American Medical Association 2006; 295:1539-48). The 48 people included men under 50 and women under 45 who were healthy but sedentary and overweight but not obese. It was hard to find people to participate: of 599 people who were screened for participation, 460 failed to meet the criteria. Another 91 people decided as they were being screened that they weren’t interested in participating. For the 48 people who did enroll, 12 served as controls and were kept on a weight-maintenance diet; 12 were assigned to a calorie restricted diet (25% restriction of their baseline energy requirements); 12 were assigned to a combination of calorie restriction and exercise (12.5% calorie restriction and 12.5% increase in energy expenditure through exercise); and 12 were assigned to a very low calorie group (890 kcal/day). Midway through the study and then at the end of the 6-month study period, all sorts of measurements were performed, including tests reflecting metabolism, tests of DNA damage, and of course weight.

What the authors found was that after six months of the prescribed regime, insulin levels and core body temperature were decreased in the intervention groups, both of which are “biomarkers of longevity.” They also found evidence of “metabolic adaptations,” i.e. lower energy expenditure in the groups on the special diets. While they could not conclude anything about whether these changes would persist if the subjects continued on their diets indefinitely and they certainly could not conclude that the subjects would live longer if they kept up the diet, they found the results “suggestive.”

The interesting aspect of this work is the possibility not that we could live longer if we starved ourselves, but rather that the aging process might be slowed down if we could find ways to emulate the effects of caloric restriction. Nobody seriously believes that large numbers of people are going to go on an 890 calorie diet indefinitely in a society where we cannot even find ways to prevent obesity or to help markedly overweight individuals lose weight. Most people aren’t really interested in living to be 100, particularly not if it means a long period of physical frailty and cognitive impairment. But if scientists could design chemicals that mimic the effects of calorie restriction and if these chemicals are able to delay aging, then conceivably all the major disorders of old age—heart disease, cancer, dementia—would have a later age of onset.

Of course it’s far from clear from a study of 48 people conducted over a mere 6 months that caloric restriction will have the desired age-delaying effect. And even if caloric restriction does prove effective, it will be a long way to finding a pill that produces the desirable consequences of caloric restriction without any significant side effects.

Before any older individuals cut down on food in the hope of preventing disability, it’s critically important to note that among older people today, malnutrition rather than obesity is a major problem. In the National Health and Nutrition Examination Survey, a study conducted periodically by the federal government, the incidence of malnutrition is reported to range between 12 and 50% among hospitalized older people and from 23-60% among institutionalized older adults. In the community, where malnutrition rates are lower, it remains a problem among people with low income, difficulty digesting or chewing food, and people who have trouble shopping or cooking (See Carol Evans, “Malnutrition in the Elderly: A Multifactorial Failure to Thrive,” Permanente Journal 2005; 9:3).

Facing our mortality is not easy. But phantasmagorical dreams of perpetual life are not the answer. What I argue in my book, The Denial of Aging: Perpetual Youth, Eternal Life, and Other Dangerous Fantasies is that immortality projects are better ways to cope with knowledge of our finitude than are searches for the elixir of life. Immortality projects—whether a book we write, a company we found, or the children we nurture—help us transform our painful awareness of our own limits into enduring memories. They are the way we leave a mark on the world, even after we ourselves have departed.

April 06, 2006

Newsweek Interview

Here's an interview Newsweek did a few days ago.