The genetics and molecular analysis of aging in Drosophila
We combine experimental, theoretical, and computational approaches to study genetic mechanisms underlying the
biology of aging. Experimentally, we couple the power of demographic analysis with advanced genetic techniques available in Drosophila
to understand the molecular mechanisms that influence age-dependent physiological deterioration in the fly. We are using modern inducible
expression systems and traditional transgenic techniques to identify genes with age-dependent effects and to characterize how such genes
interact in genetic pathways to influence the rate of aging. We are also investigating the molecular genetic basis of environmental
manipulations, such as caloric restriction, which have been shown to extend lifespan.
Aging is complex and likely to be influenced by a large number of genes, which interact through different pathways. We
are therefore very active in characterizing the system of transcription and gene expression in aging adult organisms. Using
whole-genome microarrays, we have shown that aging is a highly dynamic process in the fly, with many genes exhibiting
complicated, age-dependent patterns of expression. Understanding and simplifying this complexity is one of our goals. For
example, we find that much of the information in age-dependent profiles can be integrated into a powerful molecular
signature of aging, which might be used to characterize genetic manipulations that influence aging.
A crucial element of the research program involves the development and implementation of analytical techniques to
study the genetic basis of age-dependent traits. We are actively developing computational and statistical tools for novel
inference from large (genomic) data sets; for estimation and quantification of sources of variation in age-dependent data;
and for identification and description of treatment interactions in survival data.
Selected Publications
Jaffrezic F, Pletcher SD (2000) Statistical models for estimating the genetic basis of repeated measures and
other function-valued traits. Genetics 156:913-922.
Pletcher SD, Jaffrezic F (2002) Generalized character process models: estimating the genetic basis of traits
that cannot be observed and that change with age or environmental conditions. Biometrics 58:157-162.
Pletcher SD, Stumpf MP (2002) Population genomics: ageing by association. Current Biology 12:R328-R330.
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. Current Biology. 12:712-723.
Mair W, Goymer P, Pletcher SD, Partridge L (2003) Demography of dietary restriction and death in Drosophila.
Science 301:1731-1733.
Jaffrezic F, Thompson R, Pletcher SD (2004) Multivariate character process models for the analysis of two or
more correlated function-valued traits. Genetics 168:477-487.
Zheng J, Edelman SW, Tharmarajah G, Walker DW, Pletcher SD, Seroude L (2005) Differential patterns of apoptosis
in response to aging in Drosophila. Proceedings of the National Academy of Sciences U.S.A. 102:12083-12088.
Wertheim B, Kraaijeveld AR, Schuster E, Blanc E, Hopkins M, Pletcher SD, Strand MR, Partridge L, Godfray HC
(2005) Genome-wide gene expression in response to parasitoid attack in Drosophila. Genome Biology 6:R94.
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 Research Reviews. 4:451-480.
Libert S, Chao Y, Chu X, Pletcher SD (2006) Trade-offs between longevity and pathogen resistance in Drosophila
melanogaster are mediated by NFκB signaling. Aging Cell 5:533-543.
Contact Information
- Scott D. Pletcher, Ph.D.
- Huffington Center on Aging and
- Department of Molecular and Human Genetics
- Baylor College of Medicine
- One Baylor Plaza, N803
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-5524
- Fax: (713) 798-4161
- E-mail: pletcher@bcm.tmc.edu
|
