RESEARCH INTERESTS:

Our goal is to identify and investigate genetic mechanisms that are likely to be important for aging and age-related disease in humans by focusing on equivalent, conserved processes in the fruit fly, Drosophila melanogaster. Currently we are studying genes involved in linking diet, obesity, and immune function with aging and aging-related disease.

One area of research focuses on the phenomenon of dietary restriction, where lifespan is increased by restricting nutrient intake to roughly 65% of what animals would eat when allowed to feed ad libitum. 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 described a molecular signature of aging and used it to show that, as it does in mammals, dietary restriction delayed significant changes in gene expression that occur in many different biological processes in the aging animal. We also showed that life-long adherence to a strict dietary restriction regime is not required for flies to experience longevity-extending benefits: as little as two days of diet restriction will suffice. More recently was have shown that longevity in general (and diet restriction in particular) is regulated by olfaction and food-derived odors. Mutation of the odorant receptor gene Or83b, for example, results in flies that are broadly anosmic, long-lived, stress resistance, and fat. We are currently investigating the hypothesis that olfactory signaling is an evolutionarily conserved aging regulatory system that may be present in mammals.

We also use Drosophila as a model for studying the role of inflammatory responses on aging. These processes, which originate from the innate immune system, have been implicated as predictors/initiators of, or contributors to, chronic diseases and conditions of human aging. Mechanisms of innate immunity are highly conserved across species, and work from our laboratory and others has established that flies exhibit remarkable upregulation of innate-immunity-related genes with advancing age. Expression of these genes is dependent on NFkB-like transcription factors, which are also critical mediators of mammalian inflammation. We are testing the hypothesis that the observed activation of NFkB signaling pathways is caused by endogenous, aging-related changes in the fly that generates a condition homologous to mammalian inflammation.

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SELECTED PUBLICATIONS:
1. Libert S, Zwiener J, Chu X, Vanvoorhies W, Roman G, Pletcher SD (2007). Regulation of Drosophila life span by olfaction and food-derived odors. Science 315: 1133-1137.

2. Libert S, Chao Y, Chu X, Pletcher SD (2006). Trade-offs between longevity and pathogen resistance in Drosophila melanogaster are mediated by NFkappaB signaling. Aging Cell 5: 533-543.

3. Pletcher SD, Libert S, Skorupa D (2005). Flies and their golden apples: the effect of dietary restriction on Drosophila aging and age-dependent gene expression. Ageing Res. Rev. 4: 451-480.

4. Zheng J, Edelman SW, Tharmarajah G, Walker DW, Pletcher SD, Seroude L (2005). Differential patterns of apoptosis in response to aging in Drosophila. Proc. Natl. Acad. Sci. USA. 102: 12083-12088.

5. McCarroll SA, Murphy CT, Zou S, Pletcher SD, Chin CS, Jan YN, Kenyon C, Bargmann CI, Li H (2004). Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nat. Genet. 36: 197-204.

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

7. Pletcher SD, Macdonald SJ, Marguerie R, Certa U, Stearns SC, Goldstein DB, Partridge L (2002). Genome-Wide Transcript Profiles in Aging and Calorically Restricted Drosophila melanogaster. Curr. Biol. 12: 712-723.

8. Pletcher SD (1999). Model fitting and hypothesis testing for age-specific mortality data. J. Evol. Biol.
12: 430-440.

9. Pletcher SD, Houle D, Curtsinger JW (1998). Age-specific properties of spontaneous mutations affecting mortality in Drosophila melanogaster. Genetics 148: 287-303.

For more publications, see listing on Pub Med.

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CONTACT INFORMATION:
Scott D. Pletcher, Ph.D.
Huffington Center on Aging and
Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, N803
Houston TX 77030

Telephone: 713-798-5524
Fax: 713-798-4161
E-mail:

Pletcher lab web site: http://www.hcoa.org/scott

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