Nature Insight

Special Section on Aging in Nature Magazine (November 9, 2000).

Evolutionary history has determined that individuals thrive for long enough to produce and nurture their offspring. Thereafter, the aging process involves a slow decline in physiological vigor and an increasing susceptibility to age-related disease. Much of human culture and thinking has been shaped by the inevitability of our aging and death.

1. Thomas B. L. Kirkwood and Steven N. Austad, "Why Do We Age?," Nature, Vol. 408, pp. 233 - 238 (November 9, 2000).

The evolutionary theory of aging explains why aging occurs, giving valuable insight into the mechanisms underlying the complex cellular and molecular changes that contribute to senescence. Such understanding also helps to clarify how the genome shapes the aging process, thereby aiding the study of the genetic factors that influence longevity and age-associated diseases.

2. Toren Finkel and Nikki J. Holbrook, "Oxidants, Oxidative Stress, and the Biology of Aging," Nature, Vol. 408, pp. 239 - 247 (November 9, 2000).

Living in an oxygenated environment has required the evolution of effective cellular strategies to detect and detoxify metabolites of molecular oxygen known as reactive oxygen species. Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to aging and life span.

3. Ronald A. Depinho, "The Age of Cancer," Nature, Vol. 408, pp. 248 - 254 (November 9, 2000).

A striking link exists between advanced age and increased incidence of cancer. Here I review how several of the age-related molecular and physiological changes might act in concert to promote cancer, and in particular epithelial carcinogenesis. Experimental data indicate that the aged, cancer-prone phenotype might represent the combined pathogenetic effects of mutation load, epigenetic regulation, telomere dysfunction, and altered stromal milieu. Further verification of the role of these effects should in turn lead to the design of effective therapeutics for the treatment and prevention of cancer in the aged.

4. Leonard Guarente and Cynthia Kenyon, "Genetic Pathways that Regulate Aging in Model Organisms," Nature, Vol. 408, pp. 255 - 262 (November 9, 2000).

Searches for genes involved in the aging process have been made in genetically tractable model organisms such as yeast, Caenorhabditis elegans (nematode), Drosophila melanogaster (fruit fly), and mice. These genetic studies have established that aging is indeed regulated by specific genes, and have allowed an analysis of the pathways involved, linking physiology, signal transduction, and gene regulation. Intriguing similarities in the phenotypes of many of these mutants indicate that the mutations may also perturb regulatory systems that control aging in higher organisms.

5. George M. Martin and Junko Oshima, "Lessons from Human Progeroid Syndromes," Nature, Vol. 408, pp. 263 - 266 (November 9, 2000).

A number of human genes have been identified in which mutations can lead to the accelerated emergence of features of senescence. Studies of these genes, and of the functions of their protein products, may lead to a clearer understanding of the nature of senescence, and could provide clues for ways in which aging might be retarded.

6. Leonard Hayflick, "Commentary: The Future of Aging," Nature, Vol. 408, pp. 267 - 269 (November 9, 2000).

Advances in our knowledge of age-associated diseases have far outpaced advances in our understanding of the fundamental aging processes that underlie the vulnerability to these pathologies. If we are to increase human life expectancy beyond the fifteen-year limit that would result if today's leading causes of death were resolved, more attention must be paid to basic research on aging. Determination of longevity must be distinguished from aging to take us from the common question of why we age to a more revealing question that is rarely posed: Why do we live as long as we do? But if the ability to intervene in aging ever becomes a reality, it will be rife with unintended and undesirable consequences.