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Genetics of Longevity in Model Organisms: Debates and Paradigm Shifts

Gems, David, Partridge, Linda·2013·Annual Review of Physiology
DOI 10.1146/annurev-physiol-030212-183712
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Abstract

Discovering the biological basis of aging is one of the greatest remaining challenges for science. Work on the biology of aging has discovered a range of interventions and pathways that control aging rate. A picture is emerging of a signaling network that is sensitive to nutritional status and that controls growth, stress resistance, and aging. This network includes the insulin/IGF-1 and target of rapamycin (TOR) pathways and likely mediates the effects of dietary restriction on aging. Yet the biological processes upon which these pathways act to control life span remain unclear. A long-standing guiding assumption about aging is that it is caused by wear and tear, particularly damage at the molecular level. One view is that reactive oxygen species (ROS), including free radicals, generated as by-products of cellular metabolism, are a major contributor to this damage. Yet many recent tests of the oxidative damage theory have come up negative. Such tests have opened an exciting new phase in biogerontology in which fundamental assumptions about aging are being reexamined and revolutionary concepts are emerging. Among these concepts is the hyperfunction theory, which postulates that processes contributing to growth and reproduction run on in later life, leading to hypertrophic and hyperplastic pathologies. Here we reexamine central concepts about the nature of aging.

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  • The time-dependent accumulation of cellular damage is widely considered the general cause of aging.

    “The time-dependent accumulation of cellular damage is widely considered the general cause of aging (Gems and Partridge, 2013; Kirkwood, 2005; Vijg and Campisi, 2008).”

    From The Hallmarks of Aging (2013) · cites this paper as Gems and Partridge, 2013

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Metadata

Authors
Gems, D., & Partridge, L.
Affiliations
  • Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom
  • Max Planck Institute for Biology of Ageing, Cologne D-50931, Germany;
Venue
Annual Review of Physiology
Publisher
Annual Reviews
Published
2013-02-10
Volume
75
Issue
1
Pages
621-644
ISSN
  • 0066-4278
  • 1545-1585
DOI
10.1146/annurev-physiol-030212-183712
Cited by
499
References
30
Language
en

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