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Evidence that endurance exercise improves cardiac function in POLG mice
Author(s) -
Hill Blake,
Fu Vivian,
Ugras George,
Prolla Tomas
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.794.13
Subject(s) - mitochondrion , medicine , mitochondrial dna , biology , endocrinology , mitochondrial biogenesis , endurance training , cardiac function curve , premature aging , physiology , genetics , heart failure , gene
Aging is caused by a variety of factors, but a common thread is impaired function in the organelle central to cellular metabolism and energy production: the mitochondrion. Each cell contains ~500–1000 mitochondria (depending on tissue) and each mitochondrion contains its own DNA (~2–10 copies). The mitochondrial DNA (mtDNA) accumulate mutations with age in several species including humans and it has long been suggested that mitochondria are central to human aging. Highlighting the crucial role of mitochondria to aging, a genetic lesion that increases mtDNA damage causes premature aging. This lesion resulted in a residue substitution (D257A) in the highly conserved exonuclease domain of the sole mammalian mtDNA polymerase, POLG, impairing its proofreading ability. Homozygous knock‐in mice with the POLG‐D257A substitution (POLG mice) show a profound aging syndrome with reduced life span and premature aging including weight loss, decreased subcutaneous fat, alopecia, kyphosis, osteoporosis, anemia, reduced fertility, and cardiac dysfunction. Recently endurance exercise was shown to reverse this aging syndrome. Here the exercise protocol was repeated and followed by measurements of blood and cardiac function. Aging in POLG mice was associated with reduced levels of hemoglobin and white blood cells. Endurance exercise failed to prevent age‐related changes. By contrast, many cardiac parameters as measured by high‐resolution echocardiography showed statistically significant differences between young and old sedentary POLG mice. Statistically significant differences were also found between old POLG mice that were either sedentary or exercised. The results indicate that exercise improves some measures of cardiac dysfunction in POLG mice and suggest that interventions may exist to overcome the deleterious effects of mtDNA damage. Support or Funding Information This study was funded by a grant from Breakout Labs to CyteGen Corp. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .