Sunday, December 07, 2008

Journal of Gerontology Special Issue on Longevity

The latest issue of Journal of Gerontology: Medical Sciences is a special issue devoted to the secrets of healthy aging and longevity. This issue is further evidence of the aspiration to transcend the "disease-model" that currently shapes (and limits) medical research.

Here is a sample from the editorial of the special issue:

We have all heard stories of cigar-chomping hundred-year-olds who drink copious amounts of vodka (or other spirits) and can climb hills or swim laps faster than most fifty-year-olds. Such hardy, long-lived individuals have been a fascination of society since recorded history (1). Unfortunately, finding individuals who fit this robust description—and who possess valid birth certificates—has proven elusive. However, in the past few years, the credible study of exceptional human longevity has blossomed. In particular, more comprehensive study of long-lived individuals who are free of major clinical diseases and disability, and who might be called "exceptional survivors," is beginning (2). Some researchers believe that by studying "healthy aging" rather than focusing on specific diseases, we might find protective genetic or environmental secrets that will benefit both length and quality of life (3–5). Discovering factors that enhance odds of healthy aging and translating these findings into evidence-based interventions is becoming a research priority.

....Of great interest to gerontologists is that a subset of the exceptionally aged does seem to delay or avoid major clinical diseases and disability into their 90s or 100s (32–34). The limited autopsy data that exist on such exceptional survivors have added credibility to these remarkable clinical observations. For example, in an autopsy study of a "typical" centenarian woman in Okinawa, Bernstein and colleagues (35) found an absence of coronary artery disease, cancer, stroke, and little evidence for major damage in several organ systems. However, clear signs of "wear and tear" and past exposures had occurred including compression fractures of the spine, silicosis and scarring of the lungs, and amyloidosis in several organ systems. Larger case series of autopsies in other centenarian populations exist with a pathology burden in some individuals that is less than one might expect for 100 years of life (36,37).

In an ideal world, one would like to study aging over the life span in such individuals to more precisely assess risk and protective factors, and rates of change in health, organ function, and physical/cognitive abilities. This, however, would be a very, very long study. Therefore, most studies of exceptional survivors have traditionally had retrospective or "case-control" designs. It has been exceedingly difficult to recruit large numbers of long-lived "cases" and find age-matched, deceased "controls."

....The articles presented in this special section of the Journal represent a new and exciting direction in gerontology—a focus on health rather than disease. While some progress has been made in understanding healthy aging, much remains to be done. Phenotypes that reflect healthy aging, which are about as "complex" as they come, need further refinement in order to better understand their genetic basis. This must be accomplished before we can begin to understand the complex array of factors affecting healthy aging and longevity. Such work would be enhanced by standardization of performance-based measures of aging-related traits across populations (14), the development of consortia and/or large multiethnic cohorts for reproduction, and validation of findings and novel approaches for investigating healthy aging across the life span (41,61–63). When such criteria are met, and truly "translational" work on healthy aging is fostered, it may not be long before today's version of the "exceptional survivor" will be tomorrow's "typical" senior citizen. If this happens, the cigar-chomping, mountain-climbing supercentenarians of Shangri-La fame may not prove so elusive after all.