Late life maintenance and enhancement of functional exercise capacity in low and high responding rats after low intensity treadmill training

Lemuel A Brown; Peter C Macpherson; Lauren G Koch; Nathan R Qi; Steven L Britton; Susan V Brooks

doi:10.1016/j.exger.2019.110657

Late life maintenance and enhancement of functional exercise capacity in low and high responding rats after low intensity treadmill training

Exp Gerontol. 2019 Oct 1:125:110657. doi: 10.1016/j.exger.2019.110657. Epub 2019 Jul 12.

Authors

Lemuel A Brown¹, Peter C Macpherson¹, Lauren G Koch², Nathan R Qi³, Steven L Britton⁴, Susan V Brooks⁵

Affiliations

¹ Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States of America.
² Department of Physiology and Pharmacology, The University of Toledo, Toledo, OH, United States of America.
³ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America.
⁴ Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States of America; Department of Anesthesiology, University of Michigan, Ann Arbor, MI, United States of America.
⁵ Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, United States of America; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States of America. Electronic address: svbrooks@umich.edu.

Abstract

Intrinsic exercise capacity is predictive of both lifespan and healthspan but whether adaptive exercise capacity influences the benefits achieved from aerobic training implemented later in life is not known.

Aim: To determine if exercise late in life provides any functional improvements or underlying beneficial biochemical adaptations in rats bred to have a high response to training (HRT rats) or little to no response to training (LRT rats).

Methods: Adult (11 months) and old (22 months) female LRT and HRT rats either remained sedentary (SED) or were exercised (EXER) on a treadmill 2-3 times/week at 60% of their initial maximum running speed and distance for 4 months. At 26 months of age, exercise capacity was re-evaluated and extensor digitorum longus, gastrocnemius (GTN), and tibialis anterior (TA) muscles were excised for histological and biochemical analysis.

Results: Both SED-HRT and SED-LRT rats showed decreased exercise capacity from 22 to 26 months, but with 4 months of treadmill training, EXER-HRT rats displayed a 50% improvement in exercise capacity while EXER-LRT rats maintained pre-training levels. Protein levels of antioxidant enzymes PRDX3, CuZnSOD, and PRXV were 6-fold greater in TA muscles of aged HRT rats compared to LRT rats. PGC-1α protein levels were ~2-fold greater in GTN and TA muscles of aged HRT than in LRT rats and TFAM protein was similarly elevated in GTN muscles of aged HRT rats compared with LRT rats. BNIP3 protein levels were 5-fold greater in TA muscles of aged HRT than in LRT rats while PINK1 protein content was reduced by 78% in GTN muscles of aged HRT rats compared with LRT rats.

Conclusion: HRT rats retained the ability to improve exercise capacity into late life and that ability was associated with inherent and adaptive changes in antioxidant enzyme levels and markers of and mitochondrial quality related to healthspan benefits in aging. Moreover, low intensity exercise prevented the age-associated decline in functional exercise capacity in LRT rats.

Keywords: Aging; Antioxidant enzymes; Mitochondrial biogenesis; Nonresponders; Skeletal muscle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptation, Physiological
Animals
Antioxidants / metabolism
Exercise Tolerance*
Female
Longevity / physiology*
Male
Mitochondrial Proteins / metabolism
Muscle, Skeletal / physiology
Physical Conditioning, Animal / physiology*
Rats

Substances

Antioxidants
Mitochondrial Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding