Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis, and remodeling in the rat heart.
Aging is characterized by loss of myocytes, remodeling, and impaired contractile function in the heart. The rate of programmed cell death, or "apoptosis," in the left ventricle increases with age, and contributes to a 30% reduction in myocytes. Aging may preferentially target the Bcl-2 pathway of apoptosis in the heart. Exercise can protect cardiac function of the aging heart, although the mechanisms are poorly understood. We tested the hypothesis that 12 wk of exercise training would attenuate age-induced increases in remodeling, apoptosis, and Bax/Bcl-2 ratio in rat left ventricle. We found that exercise training provided significant protection against loss of cardiac myocytes, reduction in number of myonuclei, reactive hypertrophy of remaining myocytes, and increased connective tissue in left ventricle of the aging rat heart. Exercise training significantly attenuated age-induced increases of apoptosis in the left ventricle, as indicated by lower DNA fragmentation, TUNEL-positive staining, and caspase-3 cleavage, when compared with left ventricles from the age-matched sedentary group. Further, exercise training in the aging reduced caspase-9 levels and Bax/Bcl-2 ratio by lowering Bax protein expression while increasing Bcl-2 levels. These are the first data to demonstrate protective effects of endurance exercise training against elevated apoptosis and remodeling in the aging heart.
Kwak
Hyo-Bum
HB
Redox Biology and Cell Signaling Laboratory, Texas A&M University, College Station, Texas 77843-4243, USA.
Song
Wook
W
Lawler
John M
JM
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers; D020169:Caspases; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
C494828:Bax protein, rat; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D020169:Caspases