Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice.
Mitochondrial DNA (mtDNA) mutations are thought to have a causative role in age-related pathologies. We have shown previously that mitochondrial mutator mice (PolgD257A/D257A), harboring a proofreading-deficient version of the mtDNA polymerase gamma (POLG), accumulate mtDNA mutations in multiple tissues and display several features of accelerated aging. Calorie restriction (CR) is known to delay the onset of age-related diseases and to extend the lifespan of a variety of species, including rodents. In the current study we investigated the effects of CR on the lifespan and healthspan of mitochondrial mutator mice. Long-term CR did not increase the median or maximum lifespan of PolgD257A/D257A mice. Furthermore, CR did not reduce mtDNA deletions in the heart and muscle, accelerated sarcopenia, testicular atrophy, nor improve the alterations in cardiac parameters that are present in aged mitochondrial mutator mice. Therefore, our findings suggest that accumulation of mtDNA mutations may interfere with the beneficial action of CR in aging retardation.
Department of Aging and Geriatric Research, University of Florida, Gainesville, Florida, United States of America.
Shinichi
http://orcid.org/0000-0001-9895-6227
S
Someya
Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin, United States of America.
Gregory C
GC
Kujoth
Department of Aging and Geriatric Research, University of Florida, Gainesville, Florida, United States of America.
Mi-Jung
MJ
Kim
Department of Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.
Timothy A
TA
Hacker
Center for Mitochondrial and Epigenomic Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Marc
M
Vermulst
Veterans Administration Hospital, Geriatric Research, Education and Clinical Center, University of Wisconsin, Madison, Wisconsin, United States of America.
Richard
R
Weindruch
Departments of Genetics & Medical Genetics, University of Wisconsin, Madison, Wisconsin, United States of America.
Tomas A
TA
Prolla
D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D031204:Caloric Restriction; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D004452:Echocardiography; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009929:Organ Size / Q000235:genetics / Q000502:physiology; D013737:Testis / Q000378:metabolism
D004272:DNA, Mitochondrial; D004259:DNA-Directed DNA Polymerase