http://www.biomedcentral.com/news/20030516/02

Mild stress increases longevity

Heat shock response and insulin signal transduction combine in the control of aging

By Cathy Holding
 

Aging is a nonadaptive process resulting from cumulative damage in cells, and the genes that control oxidative or other damage may have an effect on the timescale of the aging process. Insulin also has a role in the modulation of longevity, mediated via one of the insulin-like growth factor 1 receptor (IGF1-R) signal transduction pathways. The Caenorhabditis elegans IGF1-R homolog is known as DAF-2, and daf-2 signaling negatively regulates daf-16, a forkhead transcription factor controlling expression of genes involved in metabolism and redox control. This gene has multiple targets that could be involved in modulating the several functions of the insulin-signaling pathway. In the May 16 Science, Ao-Lin Hsu and colleagues at the University of California, San Francisco, demonstrate that a molecule important in modulating heat shock response also has a role in the control of aging and that DAF-16 and the heat shock factor 1 (HSF-1) transcription factor may work together to promote longevity (Science, 300:1142-1145, 2003).

Hsu et al. demonstrated by gene knockout, overexpression, and RNA inhibition studies that, although HSF-1 functions in the DAF-2 (IGF-1) system and although DAF-16 functions in the heat shock system, both proteins function independently of each other. Using DNA microarrays, the authors found that the levels of expression of various heat-induced genes, including four small heat shock (shsp) genes, were markedly affected when either daf-2 or hsf-1 were mutated or inhibited. The authors also demonstrated that each of these shsp genes was necessary for increased longevity.

"The small heat-shock proteins also delay the onset of polyglutamine-expansion protein aggregation, suggesting that these proteins couple the normal aging process to this type of age-related disease. Because at least some of these sHSPs are likely to be functionally redundant, together they may make a substantial contribution to longevity," conclude the authors.