Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

Sira Karvinen; Mika Silvennoinen; Petra Vainio; Lea Sistonen; Lauren G Koch; Steven L Britton; Heikki Kainulainen

doi:10.1016/j.exger.2016.03.015

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

Exp Gerontol. 2016 Jun 15:79:46-54. doi: 10.1016/j.exger.2016.03.015. Epub 2016 Mar 31.

Authors

Sira Karvinen¹, Mika Silvennoinen², Petra Vainio³, Lea Sistonen⁴, Lauren G Koch⁵, Steven L Britton⁶, Heikki Kainulainen²

Affiliations

¹ Department of Biology of Physical Activity, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Jyväskylä, Finland. Electronic address: sira.karvinen@jyu.fi.
² Department of Biology of Physical Activity, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Jyväskylä, Finland.
³ Department of Biosciences, Åbo Akademi University, BioCity, Artillerigatan 6, FI -20520 Turku, Finland.
⁴ Department of Biosciences, Åbo Akademi University, BioCity, Artillerigatan 6, FI -20520 Turku, Finland; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Artillerigatan 6, FI -20520 Turku, Finland.
⁵ Department of Anesthesiology, University of Michigan Medical School, 2021 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan, USA, 48109-2200.
⁶ Department of Anesthesiology, University of Michigan Medical School, 2021 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan, USA, 48109-2200; Department of Molecular & Integrative Physiology, University of Michigan Medical School, 2021 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan, USA, 48109-2200.

PMID: 27038700
DOI: 10.1016/j.exger.2016.03.015

Abstract

Aim: Sirtuins are proteins that connect energy metabolism, oxidative stress and aging. Expression of heat shock proteins (Hsps) is regulated by heat shock factors (HSFs) in response to various environmental and physiological stresses, such as oxidative stress. Oxidative stress accumulates during aging which makes cells more prone to DNA damage. Although many experimental animal models have been designed to study the effects of knockdown or overexpression of sirtuins, HSFs and Hsps, little is known about how aging per se affects their expression. Here we study the impact of intrinsic aerobic capacity, aging and voluntary exercise on the levels of sirtuins, HSFs and Hsps in skeletal muscle.

Methods: We studied the protein levels of sirtuins (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7), HSF1, HSF2, Hsp10, Hsp27 and Hsp70 before and after one-year of voluntary running intervention of rat strains selectively bred for intrinsic aerobic exercise capacity; high capacity runners (HCR) and low capacity runners (LCR) differ by more than 30% for median lifespan. This setup enabled us to discern the effects of inborn aerobic capacity, aging and exercise activity on the protein levels of sirtuins, HSFs and Hsps in skeletal muscle.

Results: Our results revealed that the longer lived HCR rats had higher SIRT3, HSF1 and HSF2 contents in skeletal muscle (gastrocnemius, p < 0.05) than LCRs. Neither aging nor voluntary running had a significant effect on the studied sirtuin proteins. Aging significantly increased the protein levels of HSF1, HSF2 and Hsp27 (p < 0.05).

Conclusion: Our finding of elevated SIRT3 levels in HCR rats is in line with previous studies; SIRT3 in general is linked to elevated fatty acid oxidation and oxidative phosphorylation, which previously have been associated with metabolic profile of HCRs. HSF1, HSF2 and Hsp27 levels increased with aging, showing that aged muscles responded to aging-related stress. Our study shows for the first time that SIRT3 protein level is linked to high inborn aerobic capacity, and may be directly interconnected to longevity.

Keywords: aging; oxidative stress; physical activity; sirtuin; skeletal muscle.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aging / metabolism*
Animals
Body Weight / physiology
Citrate (si)-Synthase / biosynthesis
Energy Intake / physiology
Female
Heat-Shock Proteins / metabolism*
Muscle, Skeletal / metabolism*
Oxidative Stress / physiology
Physical Conditioning, Animal / physiology
Rats, Inbred Strains
Running / physiology*
Sirtuins / metabolism*

Substances

Heat-Shock Proteins
Citrate (si)-Synthase
Sirtuins

Abstract

Publication types

MeSH terms

Substances

Grants and funding