Mitochondria: A Nexus for Aging, Calorie Restriction, and Sirtuins?
Leonard Guarente






Recent studies of calorie restriction in several organisms demonstrate an increase in mitochondrial activity that is associated with the salutary effects of this dietary restriction regimen. In this Essay, I speculate on how an increase in mitochondrial activity might provide benefit and discuss how diet, mitochondria, and sirtuins might interact in a pathway to slow aging and associated diseases.

Conclusion
Mitochondria have long been proposed to play an important role in aging. Recent genetic findings in lower organisms have pinpointed sirtuins as antiaging genes, and at least four of the seven mammalian sirtuin homologs have mitochondria-associated functions. CR is perhaps the most robust intervention that extends mammalian life span and has been associated with an increase in SIRT1 levels in several tissues and a corresponding increase in mitochondrial components. Here, I have presented several models for how this increase in mitochondria may have the effect of slowing aging and disease. Some of the models rely on an important role of ROS in the aging process, whereas others do not. It is hoped that the next few years will see a further convergence of genetic pathways with mitochondrial function, which will provide a comprehensive view of aging and antiaging mechanisms and will also explain how CR works. It seems likely that we are on the right track of acquiring this understanding, and that it will involve mechanisms rich in new and old ideas about aging and how to counteract it.

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