University of Wisconsin–Madison
College of Agriculture and Life Sciences | School of Medicine and Public Health

Tomas Prolla

Professor

taprolla@wisc.edu

608-265-5204

Genetics and Medical Genetics
DNA repair, cancer and the aging process

Address
3430 Genetics/Biotech
Education
Ph.D., Yale University, (1994), Postdoctoral Research: Baylor College of Medicine
Department
Genetics and Medical Genetics
Research Interests
DNA repair, cancer and the aging process
Research Fields
Genomics, Human and Mammalian, Gene Expression, Mouse Genetics

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.


Representative Publications:
Search PubMed for more publications by Tomas Prolla

Dillon LM, Williams SL, Hida A, Peacock JD, Prolla TA, Lincoln J, Moraes CT. Increased mitochondrial biogenesis in muscle improves aging phenotypes in the mtDNA mutator mouse. Hum Mol Genet.21:2288-97, 2012.

Hiona A, Sanz A, Kujoth GC, Pamplona R, Seo AY, Hofer T, Someya S, Miyakawa T, Nakayama C, Samhan-Arias AK, Servais S, Barger JL, Portero-Otín M, Tanokura M, Prolla TA, Leeuwenburgh C. Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice. PLoS One. 7;5(7):e11468, 2010.

Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell;143:802-12, 2010.

Someya S, Xu J, Kondo K, Ding D, Salvi RJ, Yamasoba T, Rabinovitch PS, Weindruch R, Leeuwenburgh C, Tanokura M, Prolla TA. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proc. Natl. Acad. Sci. USA. 106:19432-7, 2009.

Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 309:481-4, 2005.