title: Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Sira
authors.initials: S
authors.lastname: Karvinen
authors.affiliation: Department of Biology of Physical Activity, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Silvennoinen
authors.affiliation: Department of Biosciences, Åbo Akademi University, BioCity, Artillerigatan 6, FI -20520 Turku, Finland.
authors.forename: Petra
authors.initials: P
authors.lastname: Vainio
authors.affiliation: 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.
authors.forename: Lea
authors.initials: L
authors.lastname: Sistonen
authors.affiliation: Department of Anesthesiology, University of Michigan Medical School, 2021 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan, USA, 48109-2200.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.affiliation: 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.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.affiliation: Department of Biology of Physical Activity, University of Jyväskylä, P.O. Box 35, FI-40014 University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Kainulainen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000096:biosynthesis; D002149:Energy Intake / Q000502:physiology; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology; D011919:Rats, Inbred Strains; D012420:Running / Q000502:physiology*; D037761:Sirtuins / Q000378:metabolism*
chemical_list: D006360:Heat-Shock Proteins; D002950:Citrate (si)-Synthase; D037761:Sirtuins
keywords: aging; oxidative stress; physical activity; sirtuin; skeletal muscle