DIET & AGING

A long-term focus in our lab has been on studies to identify specific genetic mechanisms of aging, and its modulation by nutrient availability, using Drosophila as a model system. Dietary restriction, where lifespan is increased by restricting nutrient intake to roughly 65% of what animals would eat when allowed to feed ad libitum promotes health and lifespan across taxa. In rodents, dietary restriction maintains most physiological processes in an apparently youthful state, and it delays the occurrence and/or progression of age-associated disease. We have shown that in Drosophila, alterations in diet composition affect behavior, metabolism, and lifespan. Providing flies with a diet rich in protein but limiting in carbohydrates produced lean, reproductively-competent animals with a reduced appetite. These results reveal that diet composition, rather than caloric intake, modulates aging, appetite, and fat storage in flies. Recent studies using rodents exposed to a broad dietary landscape suggest that our results in flies apply to mammals as well. We have identified a series of candidate mechanisms of dietary restriction, including olfactory and NFkB signaling. Most recently, we discovered that upregulation of the transsulfuration pathway (TSP) is sufficient to increase lifespan and is required for diet restriction to increase fly lifespan. In mammals, the TSP controls the metabolism of sulfur-containing amino acids including methionine, an essential amino acid. Methionine availability affects protein synthesis and methylation, and it has been implicated in murine aging (Miller et al. 2005). The relationship between transsulfuration and diet restriction has recently been shown to be present in mice. 

1. Pletcher, S. D., S. J. Macdonald, R. Marguirie, U. Certa, S. C. Stearns, D. B. Goldstein, and L. Partridge. 2002. Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster. Current Biology 12:712-723. (Featured article in Current Biology Minireview 12: R311-R312). (pubmed)

2. Mair, W., P. Goymer, S. D. Pletcher and L. Partridge. 2003. Demography of dietary restriction and death in Drosophila. Science 301:1731-1733. (pubmed)

3. McCarroll S. A., C. T. Murphy, S. G. Zou, S. D. Pletcher, C.S. Chin, Y.N. Jan, C. Kenyon, Bargmann, C.I., H. Li. 2004. Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nature Genetics 36: 197-204. (pubmed)

4. Kabil, H., O. Kabil, R. Banergee, L. Harshman, and S. D. Pletcher. 2011. Increased transulfuration mediates dietary restriction in Drosophila. PNAS. 108:16831-16836. PMCID: 3189063. (pubmed)