Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1α dependent manner

TY - JOUR

T1 - Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1α dependent manner

AU - Halling, Jens Frey

AU - Jørgensen, Stine Ringholm

AU - Olesen, Jesper

AU - Prats Gavalda, Clara

AU - Pilegaard, Henriette

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Aging is associated with impaired mitochondrial function, whereas exercise training enhances mitochondrial content and function in part through activation of PGC-1α. Mitochondria form dynamic networks regulated by fission and fusion with profound effects on mitochondrial functions, yet the effects of aging and exercise training on mitochondrial network structure remain unclear. This study examined the effects of aging and exercise training on mitochondrial network structure using confocal microscopy on mitochondria-specific stains in single muscle fibers from PGC-1α KO and WT mice. Hyperfragmentation of mitochondrial networks was observed in aged relative to young animals while exercise training normalized mitochondrial network structure in WT, but not in PGC-1α KO. Mitochondrial fission protein content (FIS1 and DRP1) relative to mitochondrial content was increased with aging in both WT and PGC-1α KO mice, while exercise training lowered mitochondrial fission protein content relative to mitochondrial content only in WT. Mitochondrial fusion protein content (MFN1/2 and OPA1) was unaffected by aging and lifelong exercise training in both PGC-1α KO and WT mice. The present results provide evidence that exercise training rescues aging-induced mitochondrial fragmentation in skeletal muscle by suppressing mitochondrial fission protein expression in a PGC-1α dependent manner.

AB - Aging is associated with impaired mitochondrial function, whereas exercise training enhances mitochondrial content and function in part through activation of PGC-1α. Mitochondria form dynamic networks regulated by fission and fusion with profound effects on mitochondrial functions, yet the effects of aging and exercise training on mitochondrial network structure remain unclear. This study examined the effects of aging and exercise training on mitochondrial network structure using confocal microscopy on mitochondria-specific stains in single muscle fibers from PGC-1α KO and WT mice. Hyperfragmentation of mitochondrial networks was observed in aged relative to young animals while exercise training normalized mitochondrial network structure in WT, but not in PGC-1α KO. Mitochondrial fission protein content (FIS1 and DRP1) relative to mitochondrial content was increased with aging in both WT and PGC-1α KO mice, while exercise training lowered mitochondrial fission protein content relative to mitochondrial content only in WT. Mitochondrial fusion protein content (MFN1/2 and OPA1) was unaffected by aging and lifelong exercise training in both PGC-1α KO and WT mice. The present results provide evidence that exercise training rescues aging-induced mitochondrial fragmentation in skeletal muscle by suppressing mitochondrial fission protein expression in a PGC-1α dependent manner.

KW - Aging

KW - Exercise

KW - Mitochondria

KW - Muscle

KW - PGC-1α

UR - http://www.scopus.com/inward/record.url?scp=85020243963&partnerID=8YFLogxK

U2 - 10.1016/j.exger.2017.05.020

DO - 10.1016/j.exger.2017.05.020

M3 - Journal article

C2 - 28577890

AN - SCOPUS:85020243963

SN - 0531-5565

VL - 96

SP - 1

EP - 6

JO - Experimental Gerontology

JF - Experimental Gerontology

ER -