Age-Related Attenuation of Aerobic Exercise Training Adaptation in 24-Week Old Rats

Abstract

Studies of age related declines in health and function often focus on the end of the lifespan. However, chronic diseases such as type 2 diabetes (T2D) develop in middle age. The purpose of this study was to determine the effect of aerobic exercise training on vascular and skeletal muscle responses in mature rats. We hypothesized that mature rats would have attenuated adaptations to exercise training. Young (Y; 12-week old; n = 8) and mature (M; 24 week-old; n = 8) male Wistar rats performed 3-weeks of treadmill running (Ex) or remained sedentary (S). After this time period, insulin and glucose were greater in mature compared with young rats (P < 0.03) and were not different with Ex. Mature rats had lower exercise capacity measured by run to fatigue distance (Y-S: 675 ± 172 vs. M-S: 585 ± 22 m; P < 0.001) and a significantly reduced change in exercise capacity in response to exercise training (Y-Ex: 2387 ± 177 vs. M-Ex: 1341 ± 161 m; P < 0.01). Ex vivo aortic function in response to phenylephrine was impaired and aortic mitochondrial respiration was elevated in mature animals (P < 0.01) and neither endpoint responded to exercise training in the mature rats. Skeletal muscle AMPK activation was 81% greater in the Y-Ex compared with Y-S and this response was attenuated (8% greater) in the M-Ex compared with M-S (P = 0.05). Similarly, muscle PGC1α was greater with exercise training in the young rats and this response was abrogated in the mature rats (P = 0.05). In summary, mature rats develop insulin resistance and have lower exercise capacity and training adaptation. Vasomotion is impaired and skeletal muscle bioenergetic adaptation to Ex is blunted. As exercise is a cornerstone of therapy for T2D, it is crucial to define the interaction between age and exercise adaptation, and to determine whether T2D modulates or accelerates the impact of age. Future studies will focus on understanding the mechanisms of this age related impairment of exercise adaptation for identification of optimal exercise training and/or pharmacological interventions. Disclosure R.L. Scalzo: None. G.F. Evans: None. S.E. Hull: None. L. Knaub: None. L.A. Walker: None. J.E. Reusch: Research Support; Self; Merck & Co., Inc.. Board Member; Self; American Diabetes Association. Research Support; Self; AstraZeneca. Other Relationship; Self; Sanofi-Aventis.