Introduction to special issue

Research on Aging: The End of the Beginning

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Science  28 Feb 2003:
Vol. 299, Issue 5611, pp. 1339-1341
DOI: 10.1126/science.299.5611.1339

Comics, poets, and sages have all expounded on what it means to age. But only now can we begin to converse about the biology of aging. Why and how do we age? Researchers have asked these questions, and some answers are finally emerging. To speed up this process, in 2001 Science, with the aid of a major gift from the Ellison Medical Foundation, launched the Science of Aging Knowledge Environment (SAGE KE). This Web site provides “one-stop shopping” for researchers in the field of aging and related disciplines. For a start, SAGE KE helps researchers keep up with the literature. We offer scientist-authored commentaries and journalist-written news stories on current research findings. Visitors to our site can find authoritative reviews written by prominent scientists and can access a storehouse of community information: case studies, discussions, a calendar of meetings on aging, a database of genes/interventions and mouse models related to aging, and a directory of people working in the field. In addition, SAGEKE houses a virtual journal whose search engine is trained to find new papers on aging no matter where they are published. Access to SAGE KE is free until 26 March 2003.

In this joint special issue, Science and SAGE KE have teamed up to showcase highlights from what might be called the “end of the beginning” of research on aging. We have focused on physiological mechanisms underlying processes of aging, rather than on the large array of debilitating and costly disorders that so commonly emerge during the latter half of the life-spans of human beings. The reason for this decision is illustrated in the figure on page 1341. The “one disorder at a time” approach has limited power to delay death; rather, it is through deciphering the biological underpinnings of processes of aging that scientists will likely discover ways to extend the human life-span. This problem is being attacked from several angles, and we are seeing some emerging themes.

Feeding fewer calories to rodents—and likely primates too—makes them more stress-resistant and, perhaps because they are more stress-resistant, they live considerably longer. Several other animal model systems have mutation-induced metabolic states that are similar to those produced by calorie restriction and are also designed for withstanding adverse conditions—the dauer phase in the worm Caenorhabditis elegans, for example. These mechanisms are probably related to ancient and adaptive types of diapauses: time-outs from the business of reproduction while awaiting more favorable conditions. In their Review, Longo and Finch (p. 1342) compare these long-lived creatures, ranging from yeast to mice, and point out the commonalties, such as defects in the insulin/insulin-like growth factor 1 signaling pathway. In SAGE KE, Masoro surveys the history of research on calorie restriction, and Hopkin explores the downside of eating less. It turns out to be more than just hunger pangs.


Genetic approaches in model systems have been a gold mine in divulging which processes can tune life-span up or down. And, when interpreted in the context of more traditional endocrinological approaches, genetic results point to endocrine regulation of critical life-span-controlling functions as a possible common pathway, as summarized in Tatar et al.'s Review (p. 1346). In SAGE KE, Davenport explores new research that probes how well phenomena observed in the lab relate to those that occur in natural environments.

What are the critical downstream functions that are important for aging? Several answers are on the table, and they may well all be right. Some lines of evidence point to silencing of the expression of certain genes as a key regulator, argue Hekimi and Guarente in their Review (p. 1351), although the cumulative damage inflicted by reactive oxygen species is also a likely culprit. Indeed, in their Review, Hasty and co-workers (p. 1355) summarize how damage to DNA, perhaps by such oxygen radicals, can be better understood as a cause of aging through the comparison of clinical syndromes and mouse models. In SAGE KE, Shcherbakova and colleagues zero in on the DNA polymerases, which repair DNA damage, at least when they are working optimally; and Walter et al. examine the special case of germline genome stability.

But the topic of aging is far broader than genes and hormones and ultimately affects all of our daily lives in one way or another. For researchers in the field, their pursuits in the lab can also have a personal component, as seen firsthand in Guarente's book Ageless Quest, reviewed by Promislow in this issue (p. 1319). And for many, aging can be painful, as is poignantly clear in Bush's review of DeBaggio's recent book recounting his own experiences with Alzheimer's disease (p. 1318). But there is some good news. Two News stories by Helmuth, one in Science (p. 1300) and one on SAGE KE, give us some reasons for looking forward to the latter half of our lives. Scores on vocabulary tests appear to improve with age, and older people often outperform younger ones in interpersonal tasks.

Research on aging is increasingly important in the public policy arena as well. The Policy Forum by Juengst (p. 1323) argues that we need to start thinking about the practical and ethical ramifications of research on aging now, before the decisions are made for us by circumstance. We at Science also believe that public debate on issues surrounding aging is essential. Consequently we will be launching, in March 2003, a new portal of SAGE KE to catalyze public discourse about issues surrounding aging. Built in partnership with the Alliance for Aging Research, this new site—called SAGE Crossroads—will feature a series of Webcast debates and interviews in which prominent figures discuss controversies in research and policies on aging. The first Webcast—a discussion between Francis Fukuyama and Ronald Bailey entitled “The Future of Aging: Pitfalls and Possibilities”—occurred on 12 February and focused on the ethics of prolonging life. This debate, plus related news stories, discussions, and other resources, can be seen at SAGECrossroads. net. Scientific research on biological mechanisms of aging may be at the end of the beginning, but the larger discussions of why we study aging and the proper use for this knowledge are yet in their infancy.

Actor Charlie Chaplin once remarked that “we are all amateurs; we don't live long enough to become anything else.” If aging processes could be attenuated, humans would have additional healthy years to bring their personal goals to fruition. The challenge to society will be to ensure that those goals are compatible with the needs of humanity.

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