Table 1.

A selection of Evolutionarily Conserved Longevity Determinants

A small number of genes or interventions are known to increase life span in different model organisms. A selection of these are shown here.

Antioxidant enzymes — Increased expression of antioxidant enzymes, such as superoxide dismutase and catalase increase life span in yeast, flies, and mice [23, 26–29]. The free radical theory of aging posits that many age-associated phenotypes result from damage caused by oxidative free radicals, which are likely to be reduced by increased expression of antioxidant enzymes [30].

Dietary restriction (calorie/caloric restriction) — Dietary restriction increases life span in yeast, worms, flies, mice, rats, and other organisms [31, 32]. The mechanisms by which dietary restriction promotes longevity and retards disease remain unknown, although several hypotheses have been proposed.

Insulin/IGF-1 — Mutations that decrease insulin/IGF-1-like signaling increase life span in worms, flies, and mice [33–35].

Resveratrol — Increases life span in fish, worms, and flies [36, 37]. Resveratrol is a polyphenolic compound found in red wine and grapes that acts on several cellular proteins, including sirtuins, AMP kinase, mitochondrial ATP synthase and complex III, fatty acid synthase, protein kinase C, p53, MEK1, TNF– and NFκB [38].

Ribosomal Proteins — Deletion or RNAi inhibition of individual ribosomal proteins increases life span in yeast and worms [6, 13, 39].

S6 Kinase — Decreased S6 kinase activity increases life span in worms and flies [14, 21]. S6 kinase is a TOR target that promotes ribosome maturation.

Sch9/Akt — Deletion of Sch9 increases life span in yeast and RNAi of Akt isoforms increases life span in C. elegans [3, 24, 40, 41].

Sirtuins — Increased activity of Sir2 orthologs increases life span in yeast, worms, and flies [42–44].

TOR — Mutations that decrease activity of the nutrient-responsive TOR kinase increase life span in yeast, worms, and flies [6, 7, 19–21].