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Science 305 (5689): 1419-

Copyright © 2004 by the American Association for the Advancement of Science

Deconstructing Aging

Lisa Chong, Heather McDonald, and Evelyn Strauss

Contents
News
Coming to Grips With Bone Loss
Viewpoint
Aging in Rhesus Monkeys: Relevance to Human Health Interventions
G. S. Roth, J. A. Mattison, M. A. Ottinger, M. E. Chachich, M. A. Lane, D. K. Ingram
Review
What Can Progeroid Syndromes Tell Us About Human Aging?
D. Kipling, T. Davis, E. L. Ostler, R. G. A. Faragher
See related STKE and
SAGE KE material
, and Editorial.
Experts argue about what drives our decline over time, but most would agree about one hallmark feature of aging: It predisposes our bodies to fall apart. Organs, tissues, and even individual cells start misbehaving, rendering us susceptible to the familiar conditions that, for example, weaken our bones, scramble our neural messages, and condemn us to pain. This special joint issue of Science and two of its online sites, Science of Aging Knowledge Environment (SAGE KE) and Signal Transduction Knowledge Environment (STKE), explores how we age piece by piece.

Two articles focus on osteoporosis, a disease that undermines our skeletons. In a News story (p. 1420), Marx looks at some of the recent trends in research on this debilitating illness, with particular emphasis on the therapies that drug designers are developing to combat it. In an STKE Review (www.sciencemag.org/sciext/aging2004), Hughes-Fulford examines signaling pathways involved in the proliferation of bone-building cells--osteoblasts--in response to mechanical stress, such as weight-bearing exercise. Mechanical stress can even counteract some of the bone-weakening effects of estrogen loss after menopause.

Like our bones, the cartilage that promotes smooth joint movement can break down with age. In SAGE KE (www.sciencemag.org/sciext/aging2004), a Case Study by Shakoor and Loeser describes the ravages of osteoarthritis, a major cause of disability and chronic pain in the elderly.

People with Werner syndrome display the premature onset of not only osteoporosis and osteoarthritis but many other age-related conditions. In their Review (p. 1426), Kipling et al. present evidence from investigations of this disease that suggests that somatic cell senescence promotes normal aging. A Viewpoint by Roth et al. (p. 1423) discusses another model for studying aging: nonhuman primates. Many similar age-related perturbations occur in rhesus monkeys and humans. In both creatures, for instance, concentrations of dehydroepiandrosterone sulfate (DHEAS) wane with increasing age. Blood-borne quantities of this compound are higher than normal in monkeys subjected to the life-extending regime of calorie restriction and in long-lived men. A SAGE KE Review by Hornsby explores the mechanisms by which the DHEAS- secreting adrenal cortex might change as we grow older.

Although the lethargy of many physiological activities seems to encourage aging, the exuberance of others might also contribute to our downfall. A SAGE KE Perspective by Mobbs probes the idea that neuroendocrine activity involving the pituitary, reproductive, or adrenal systems fosters age-related decay.

As researchers gain insight into how we disintegrate, they also are striving to renew our tired bodies. Kennedy points out in his Editorial (p. 1369) that stretching longevity without such bolstering of our ailing systems would be an unwelcome tradeoff. In a SAGE KE News story, Davenport surveys regeneration biology--an ancient field that is feeling new life from the application of modern genetic techniques. Using historical records as well as current interview material, a SAGE KE News story by Chen delves into the parallels between the public's responses to in vitro fertilization in the 1970s and to stem cell technology today. Time will tell whether emerging stem cell-based technology will evolve into a routine fixture of medical practice, as test tube baby-making has.

These articles detail attempts to understand the body's unraveling and to counteract it. Through such a piece-by-piece approach, answers to the mystery of aging are bound to come together.



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