Today I thought I'd share a readable overview of presently discovered longevity genes: how they fit into a small number of broad categories, and are surprisingly similar across a range of different organisms. It's an open access paper, so don't miss the PDF link underneath the abstract.

Longevity Genes: Insights from Calorie Restriction and Genetic Longevity Models

In this review, we discuss the genes and the related signal pathways that regulate aging and longevity by reviewing recent findings of genetic longevity models in rodents in reference to findings with lower organisms. We also paid special attention to the genes and signals mediating the effects of calorie restriction, a powerful intervention that slows the aging process and extends the lifespan in a range of organisms.

An evolutionary view emphasizes the roles of nutrient-sensing and neuroendocrine adaptation to food shortage as the mechanisms underlying the effects of CR. Genetic and non-genetic interventions without CR suggest a role for single or combined hormonal signals that partly mediate the effect of CR.

Longevity genes fall into two categories, genes relevant to nutrient-sensing systems and those associated with mitochondrial function or Redox regulation. In mammals, disrupted or reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling robustly favors longevity. CR also suppresses the GH-IGF-1 axis, indicating the importance of this signal pathway.

Surprisingly, there are very few longevity models to evaluate the enhanced anti-oxidative mechanism, while there is substantial evidence supporting the oxidative stress and damage theory of aging. Either increased or reduced mitochondrial function may extend the lifespan. The role of Redox regulation and mitochondrial function in CR remains to be elucidated.

It is my impression from watching this all develop for some few years that mitochondrial research is where the big payoff is in the mainstream of aging research - those researchers who are not yet thinking along the lines of damage repair strategies, but are instead moving ahead with a slower approach. Half the field is working on a range of interconnected metabolic control mechanisms, which I can't see producing anywhere near as dramatic results as quickly as a full-court press towards repairing mitochondrial damage. Even somewhat slowing oxidative damage to mitochondria produces gains in life span in mice that are on the same order as that of calorie restriction - imagine what we could do with one of the more comprehensive mitochondrial repair technologies presently under development.