Hyperactivation of p53 leads to a reduction in tumor formation and an unexpected shortening of life span in two different model systems . The decreased life span occurs with signs of accelerated aging, such as osteoporosis, reduction in body weight, atrophy of organs, decreased stress resistance, and depletion of hematopoietic stem cells. These observations suggest a role for p53 in the determination of life span and the speculation that decreasing p53 activity may result in positive effects on some aging phenotypes . In this report, we show that expression of dominant-negative versions of Drosophila melanogaster p53 in adult neurons extends life span and increases genotoxic stress resistance in the fly. Consistent with this, a naturally occurring allele with decreased p53 activity has been associated with extended survival in humans . Expression of the dominant-negative Drosophila melanogaster p53 constructs does not further increase the extended life span of flies that are calorie restricted, suggesting that a decrease in p53 activity may mediate a component of the calorie-restriction life span-extending pathway in flies.

Loss of an olfactory receptor that senses carbon dioxide increases longevity and fecundity and alters overall physiology in fruit flies.

No abstract

In several species, immune signaling networks are emerging as critical modulators of disease resistance, energy metabolism, and aging. In this issue of Cell Metabolism, Ren et al. (2007) lay the groundwork for dissecting the mechanisms of this coordination by characterizing the interplay between microbial pathogens and aging in the fly.