Coming of age: molecular drivers of aging and therapeutic opportunities
Christopher B. Newgard, Norman E. Sharpless
Christopher B. Newgard, Norman E. Sharpless
Published March 1, 2013
Citation Information: J Clin Invest. 2013;123(3):946-950. https://doi.org/10.1172/JCI68833.
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Review Series

Coming of age: molecular drivers of aging and therapeutic opportunities

Abstract

Aging is like the weather: everyone talks about it, but no one seems to do anything about it. We believe this may soon change, as an improved understanding of the molecular and genetic pathways underlying aging suggests it is possible to therapeutically target the aging process and increase health span. This Review series focuses on fundamental cellular mechanisms of aging and their relationship to human disease. These pathways include telomere dysfunction in cellular senescence and induction of the senescence-associated secretory phenotype (SASP) in systemic aging, sirtuin family regulation of metabolism and aging-associated diseases, mitochondrial metabolism in aging, the mechanistic target of rapamycin (mTOR) signaling pathway and the use of mTOR inhibitors to increase longevity, the progressive decline of the immune system with age, and aging-associated changes to pancreatic islet β cells that may contribute to diabetes. Together, these articles explore pathways affecting aging and possible interventional targets to slow or delay the onset of age-related pathologies.

Authors

Christopher B. Newgard, Norman E. Sharpless

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Figure 1

Molecular pathways implicated in aging.

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Molecular pathways implicated in aging. Molecular pathways that drive ce...
Molecular pathways that drive cellular senescence may contribute to aging and age-related diseases by disrupting tissue homeostasis through impaired stem cell renewal and by promoting the spread of senescence and inducing chronic inflammation through the SASP. Reviews in this series highlight several of these pathways, including the contribution of telomere dysfunction to age-associated disease (24), the mTOR signaling pathway and mechanisms underlying mTOR inhibitors in increasing longevity (13), the role of the sirtuin family of proteins in regulating metabolism and aging-associated diseases (16), the role of mitochondrial dysfunction in aging, including caveats of the long-held free radical hypothesis of aging (8), and the role of cellular senescence and the induction of the SASP in systemic aging (23). The SASP may promote increased tissue inflammation and dysfunction, which leads to aging phenotypes such as the decline in immune system function (26). Aging also decreased β cell regeneration in pancreatic islets (25).