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Research Lab
Molecular genetic approach
With Drosophila melanogaster we investigate mutations that affect
rates of aging. Mutants of the insulin-like receptor (InR) increase
life span by 50-85%. InR is a homolog of C. elegans daf-2, which
was among the first genes recognized to modulate aging. Mutants
of InR possess many phenotypes that could extend life: high fat
content, small body size and reduced fecundity. We found that reduce
fecundity results from deficiency of the endocrine juvenile hormone,
and that this hormonal itself is sufficient to modulate adult aging
in the fly.
Our current aim is to understand how insulin and the insulin-like
receptor modulate neuroendocrine synthesis of juvenile hormone,
and in turn how this hormone affects somatic traits with respect
to aging. Our strategy is to integrate genetic, molecular and physiological
techniques to develop a comprehensive model for the regulation and
cause of Drosophila aging.
Biology of aging in natural populations
Melanoplus grasshoppers of the Sierra Nevada occur along an elevational
gradient. Populations are genetically differentiated in a number
of life history traits; senescence is fastest in adults from high
elevations. In the laboratory, we use stocks derived from field
populations to explore the genetic and demographic basis of aging.
Our current aim is to distinguish the relative importance of pleiotropy
versus mutation and drift as the genetic basis of senescence evolution.
One future goal is to return to the field and establish whether
the age-specific patterns of natural selection are sufficient to
predict the evolved patterns of aging revealed by detailed laboratory
demographics.
Drosophila also provide opportunities to assess the ecological
context of senescence evolution. Endemic Drsophila of Japan and
of Finland overwinter as adults in a state of photoperiod induced
reproductive diapause. We find that this diapause is associated
with negligible rates of aging. With these endemic species we are
beginning to explore the physiological basis of senescence plasticity.
We hope to extend this work into the realm of comparative genomics
through the cross-hybridization of with D. melanogaster spotted
arrays.
Somatic and reproductive aging in primates
Baboons are perhaps the best primate model to study the genetics
and demography of aging. Wild populations in East Africa reveal
robust patterns of demographic senescence that are mirrored by a
captive population at the Southwest Regional Primate Center. In
collaboration with field, clinical and laboratory scientists I am
developing an initiate to characterize the aging phenotypes of baboon
and to genetically map loci that lead to differences in senescence
and female perimenopause.
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