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Research Description:
My research program is focused on understanding the molecular basis of the aging process and its retardation by caloric restriction. Our studies have uncovered a central role for mitochondria and energy metabolism in both aging and its retardation by caloric restriction. We use the mouse as model system and most of our studies are based on the construction of mouse models of accelerated or retarded aging. We generate these models through the use of gene targeting in ES cells, as well as transgenic animal construction. An example of such work from our Laboratory is a widely used model of age-related mitochondrial dysfunction, mice deficient in the exonuclease domain of the mitochondrial DNA polymerase gamma (PolgD257A).
We have previously used DNA microarrays to shown that caloric restriction leads to a “metabolic reprogramming” at the transcriptional level. Our more recent studies have focused on the role of the sirtuin SIRT3 in mediating the beneficial effects of caloric restriction in aging, including such metabolic reprogramming. SIRT3 is a NAD+ dependent deacetylase located in the mitochondrial matrix that induces metabolic shifts in response to caloric restriction. Such metabolic shifts appear to increase oxidative stress resistance and prevent an increase in age-related apoptosis. We are investigating if this metabolic adaptation underlies the beneficial effects of caloric restriction in age-related diseases as well as age-related physiological declines. The long-term goal of our studies is to identify critical pathways in aging and find either natural or synthetic compounds that modulate such pathways in a favorable manner.
Research Interests
Papers共 163 篇Author StatisticsCo-AuthorSimilar Experts
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Modern Pathologyno. 12 (2023): 100332-100332
Rashpal S. Dhillon, Yiming Qin,Paul R. van Ginkel,Vivian Fu,James M. Vann,Alexis J. Lawton,Cara L Green, Fúlvia de Barros Manchado-Gobatto,Cláudio Alexandre Gobatto,Dudley W. Lamming,Tomas A. Prolla,John M. Denu
Aging Cellno. 12 (2022)
biorxiv(2022)
Skeletal Muscleno. 1 (2021)
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