Jonathan Wanagat

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Mitochondrial DNA (mtDNA) mutations are thought to have a causal role in many age-related pathologies. Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and provide evidence for a homology-directed DNA repair mechanism in mitochondria that is directly linked to the formation of mtDNA(More)
Mitochondrial defects have been found in aging and several age-related diseases. Mice with a homozygous mutation in the exonuclease encoding domain of mitochondrial DNA polymerase gamma (Polg(m/m)) are prone to age-dependent accumulation of mitochondrial DNA mutations and have shown a broad spectrum of aging-like phenotypes. However, the mechanism of(More)
We hypothesized that cardiac aging in the rat involves mitochondrial genetic damage and mitochondrial enzymatic dysfunction of individual cardiomyocytes as has been demonstrated previously only in primate myocardium. Myocardium from Fischer 344 x Brown Norway F(1)hybrid rats of ages 5, 18 and 36-38 months was examined for mitochondrial genetic and enzymatic(More)
Adult-onset calorie restriction (A-CR) is an experimental model of life extension and healthy aging less explored, compared with calorie restriction begun at early ages, but one more realistic for human application. We examined the effect of A-CR on the aging rat kidney with respect to common structural age-dependent changes and the accumulation of(More)
The effects of aging on cardiovascular function and cardiac structure were determined in a rat model recommended for gerontological studies. A cross-sectional analysis assessed cardiac changes in male Fischer 344 x Brown Norway F1 hybrid rats (FBN) from adulthood to the very aged (n = 6 per 12-, 18-, 21-, 24-, 27-, 30-, 33-, 36-, and 39-mo-old group). Rats(More)
Interleukin-6 (IL-6) is a member of the family of cytokines collectively termed "the interleukin-6 type cytokines." Among its many functions, IL-6 plays an active role in immunology, bone metabolism, reproduction, arthritis, neoplasia, and aging. IL-6 expression is regulated by a variety of factors, including steroidal hormones, at both the transcriptional(More)
The hypothesis that the accumulation of electron transport system (ETS) abnormalities and sarcopenia are linked was investigated. Vastus lateralis, soleus, and adductor longus muscles were studied in 5-, 18-, and 36-mo-old male Fischer 344 x Brown Norway F(1) hybrid rats. A significant decrease in soleus and vastus lateralis muscle mass was observed with(More)
Exciting new studies are increasingly strengthening the link between mitochondrial mutagenesis and tumor progression. Here we provide a comprehensive review and meta-analysis of studies reporting on mitochondrial DNA mutations in common human cancers. We discuss possible mechanisms by which mitochondrial DNA mutations may influence carcinogenesis, outline(More)
Hacker, Timothy A., Susan H. McKiernan, Pamela S. Douglas, Jonathan Wanagat, and Judd M. Aiken. Age-related changes in cardiac structure and function in Fischer 344 Brown Norway hybrid rats. Am J Physiol Heart Circ Physiol 290: H304–H311, 2006. First published September 2, 2005; doi:10.1152/ajpheart.00290.2005.— The effects of aging on cardiovascular(More)
Impaired estrogen receptor α (ERα) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we established that reduced ERα expression in muscle is associated with(More)