About

Tomas Prolla is a Professor in the Department of Genetics at the University of Wisconsin–Madison. He earned his Ph.D. from Yale University in 1994 and completed postdoctoral research at Baylor College of Medicine in the Department of Genetics and Medical Genetics. His research program is focused on understanding the molecular basis of the aging process and its retardation by caloric restriction. His studies have uncovered a central role for mitochondria and energy metabolism in aging and its modulation through caloric restriction. He uses the mouse as a model system, constructing models of accelerated or retarded aging through gene targeting in embryonic stem cells and transgenic animal construction. Notably, his laboratory has developed a widely used model of age-related mitochondrial dysfunction involving mice deficient in the exonuclease domain of mitochondrial DNA polymerase gamma (PolgD257A). His research has shown that caloric restriction leads to metabolic reprogramming at the transcriptional level, with a focus on the role of the sirtuin SIRT3 in mediating the beneficial effects of caloric restriction in aging. SIRT3, a NAD+ dependent deacetylase located in the mitochondrial matrix, induces metabolic shifts that increase oxidative stress resistance and prevent age-related apoptosis. His long-term goal is to identify critical pathways in aging and find natural or synthetic compounds that modulate these pathways in a favorable manner.

Research topics

• Genetics
• Biology
• Endocrinology
• Pathology
• Medicine
• Anatomy
• Biochemistry
• Internal medicine

Selected publications

• Somatostatin Receptor Type 2 and Thyroid-Stimulating Hormone Receptor Expression in Oncocytic Thyroid Neoplasms: Implications for Prognosis and Treatment

  Modern Pathology · 2023-09-15 · 9 citations

  articleOpen access
  PublisherOA PDFDOI

• Living high - training low model applied to C57BL/6J mice: Effects on physiological parameters related to aerobic fitness and acid-base balance

  Life Sciences · 2023-01-26 · 6 citations

  article
  PublisherDOI

• SIRT3 deficiency decreases oxidative-metabolism capacity but increases lifespan under caloric restriction

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-05-10

  preprintOpen accessCorresponding

  Summary Mitochondrial NAD + -dependent protein deacetylase Sirtuin3 (SIRT3) has been proposed to mediate calorie restriction (CR)-dependent metabolic regulation and lifespan extension. Here, we investigated the role of SIRT3 in CR-mediated longevity, mitochondrial function, and aerobic fitness. We report that SIRT3 is required for whole-body aerobic capacity but is dispensable for CR-dependent lifespan extension. Under CR, loss of SIRT3 ( Sirt3 -/- ) yielded a longer overall and maximum lifespan as compared to Sirt3 +/+ mice. This unexpected lifespan extension was associated with altered mitochondrial protein acetylation in oxidative metabolic pathways, reduced mitochondrial respiration, and reduced aerobic exercise capacity. Also, Sirt3 -/- CR mice exhibit lower physical activity and favor fatty acid oxidation during the postprandial period, leading to a pseudo-fasting condition that extends the fasting period. This study shows uncoupling of lifespan and healthspan parameters (aerobic fitness and spontaneous activity), and provides new insights into SIRT3 function in CR adaptation, fuel utilization, and aging.

  PublisherOA PDFDOI

• <scp>SIRT3</scp> deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction

  Aging Cell · 2022 · 24 citations

  • Biology
  • Endocrinology
  • Biochemistry

  CR mice exhibit lower spontaneous activity and a trend favoring fatty acid oxidation during the postprandial period. This study shows the uncoupling of lifespan and healthspan parameters (aerobic fitness and spontaneous activity) and provides new insights into SIRT3 function in CR adaptation, fuel utilization, and aging.

  PublisherOA PDFDOI

• Aerobic training associated with an active lifestyle exerts a protective effect against oxidative damage in hypothalamus and liver: The involvement of energy metabolism

  Brain Research Bulletin · 2021-07-22 · 10 citations

  article
  PublisherDOI

• Roles of Bak and Sirt3 in Paraquat-Induced Cochlear Hair Cell Damage

  Neurotoxicity Research · 2021-04-26 · 7 citations

  articleOpen access
  PublisherOA PDFDOI
• RETRACTED

  Retraction Note to: Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice

  Skeletal Muscle · 2021-03-30 · 2 citations

  retraction

  An amendment to this paper has been published and can be accessed via the original article.

  PublisherOA PDFDOI

• Prematurely aging mitochondrial DNA mutator mice display subchondral osteopenia and chondrocyte hypertrophy without further osteoarthritis features

  Scientific Reports · 2020 · 32 citations

  • Medicine
  • Endocrinology
  • Pathology

  mice displayed a specific bone phenotype characterized by osteopenia of epiphyseal trabecular bone and subchondral cortical plate. Trabecular thickness was significantly associated with osteocyte apoptosis rates and osteoclasts numbers were increased in subchondral bone tissues. While chondrocyte apoptosis rates in articular and growth plate cartilage were similar between groups, homozygous mitochondrial DNA mutator mice displayed elevated numbers of hypertrophic chondrocytes in articular calcified cartilage. Low grade cartilage degeneration, predominantly loss of proteoglycans, was present in all genotypes and the development of osteoarthritis features was not found accelerated in premature aging. Somatically acquired mitochondrial DNA mutations predispose to elevated subchondral bone turnover and hypertrophy in calcified cartilage, yet additional mechanical or metabolic stimuli would seem required for induction and accelerated progression of aging-associated osteoarthritis.

  PublisherOA PDFDOI

• A Novel Micronutrient Blend Mimics Calorie Restriction Transcriptomics in Multiple Tissues of Mice and Increases Lifespan and Mobility in C. elegans

  Nutrients · 2020-02-14 · 10 citations

  articleOpen access

  Background: We previously described a novel micronutrient blend that behaves like a putative calorie restriction mimetic. The aim of this paper was to analyze the beneficial effects of our micronutrient blend in mice and C. elegans, and compare them with calorie restriction. Methods: Whole transcriptomic analysis was performed in the brain cortex, skeletal muscle and heart in three groups of mice: old controls (30 months), old + calorie restriction and old + novel micronutrient blend. Longevity and vitality were tested in C. elegans. Results: The micronutrient blend elicited transcriptomic changes in a manner similar to those in the calorie-restricted group and different from those in the control group. Subgroup analysis revealed that nuclear hormone receptor, proteasome complex and angiotensinogen genes, all of which are known to be directly related to aging, were the most affected. Furthermore, a functional analysis in C. elegans was used. We found that feeding C. elegans the micronutrient blend increased longevity as well as vitality. Conclusions: We describe a micronutrient supplement that causes similar changes (transcriptomic and promoting longevity and vitality) as a calorie restriction in mice and C. elegans, respectively, but further studies are required to confirm these effects in humans.

  PublisherOA PDFDOI

• Establishment of Quantitative PCR Assays for Active Long Interspersed Nuclear Element-1 Subfamilies in Mice and Applications to the Analysis of Aging-Associated Retrotransposition

  Frontiers in Genetics · 2020 · 11 citations

  • Biology
  • Genetics

  mice showed higher levels of the type GfII LINE-1 in the basal ganglia than the wild-type mice did, highlighting the importance of assays that focus on an individual active LINE-1 subfamily.

  PublisherDOI

Recent grants

• NIH Grant R01AG021905

  NIH · $2.0M · 2009

• NIH Grant R01CA078723

  NIH · $699k · 2003

• NIH Grant R01AG020681

  NIH · $1.5M · 2009

• NIH Grant R01AG038679

  NIH · $1.6M · 2017

Frequent coauthors

• Richard Weindruch

  102 shared

• Gregory C. Kujoth

  University of Wisconsin–Madison

  63 shared

• Shinichi Someya

  University of Florida

  43 shared

• David B. Allison

  31 shared

• Christiaan Leeuwenburgh

  University of Florida

  31 shared

• Tsuyoshi Kayo

  28 shared

• Masaru Tanokura

  The University of Tokyo

  26 shared

• Jason D. Morrow

  The University of Texas Health Science Center at San Antonio

  26 shared

Labs

• Laboratory of GeneticsPI

Education

• Ph.D., Genetics

  University of Wisconsin–Madison

  2000

• M.S., Genetics

  University of Wisconsin–Madison

  1996

• B.S., Genetics

  University of Wisconsin–Madison

  1994