Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice

Michael P. Siegel, Shane E. Kruse, Justin Percival, Jorming Goh, Collin C. White, Heather C. Hopkins, Terrance J. Kavanagh, Hazel H. Szeto, Peter S. Rabinovitch, David J. Marcinek

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Mitochondrial dysfunction plays a key pathogenic role in aging skeletal muscle resulting in significant healthcare costs in the developed world. However, there is no pharmacologic treatment to rapidly reverse mitochondrial deficits in the elderly. Here, we demonstrate that a single treatment with the mitochondrial-targeted peptide SS-31 restores in vivo mitochondrial energetics to young levels in aged mice after only one hour. Young (5 month old) and old (27 month old) mice were injected intraperitoneally with either saline or 3 mg kg-1 of SS-31. Skeletal muscle mitochondrial energetics were measured in vivo one hour after injection using a unique combination of optical and 31P magnetic resonance spectroscopy. Age-related declines in resting and maximal mitochondrial ATP production, coupling of oxidative phosphorylation (P/O), and cell energy state (PCr/ATP) were rapidly reversed after SS-31 treatment, while SS-31 had no observable effect on young muscle. These effects of SS-31 on mitochondrial energetics in aged muscle were also associated with a more reduced glutathione redox status and lower mitochondrial H2O2 emission. Skeletal muscle of aged mice was more fatigue resistant in situ one hour after SS-31 treatment, and eight days of SS-31 treatment led to increased whole-animal endurance capacity. These data demonstrate that SS-31 represents a new strategy for reversing age-related deficits in skeletal muscle with potential for translation into human use.

Original languageEnglish
Pages (from-to)763-771
Number of pages9
JournalAging Cell
Volume12
Issue number5
DOIs
StatePublished - Oct 1 2013

Fingerprint

Skeletal Muscle
Peptides
Adenosine Triphosphate
Therapeutics
Muscles
Oxidative Phosphorylation
Health Care Costs
Oxidation-Reduction
Fatigue
Glutathione
Magnetic Resonance Spectroscopy
Injections

Keywords

  • Aging
  • Mitochondria
  • Oxidative stress
  • Sarcopenia
  • Skeletal muscle

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. / Siegel, Michael P.; Kruse, Shane E.; Percival, Justin; Goh, Jorming; White, Collin C.; Hopkins, Heather C.; Kavanagh, Terrance J.; Szeto, Hazel H.; Rabinovitch, Peter S.; Marcinek, David J.

In: Aging Cell, Vol. 12, No. 5, 01.10.2013, p. 763-771.

Research output: Contribution to journalArticle

Siegel, MP, Kruse, SE, Percival, J, Goh, J, White, CC, Hopkins, HC, Kavanagh, TJ, Szeto, HH, Rabinovitch, PS & Marcinek, DJ 2013, 'Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice', Aging Cell, vol. 12, no. 5, pp. 763-771. https://doi.org/10.1111/acel.12102
Siegel, Michael P. ; Kruse, Shane E. ; Percival, Justin ; Goh, Jorming ; White, Collin C. ; Hopkins, Heather C. ; Kavanagh, Terrance J. ; Szeto, Hazel H. ; Rabinovitch, Peter S. ; Marcinek, David J. / Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. In: Aging Cell. 2013 ; Vol. 12, No. 5. pp. 763-771.
@article{492219785aa040f5aac0c4c1302580a8,
title = "Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice",
abstract = "Mitochondrial dysfunction plays a key pathogenic role in aging skeletal muscle resulting in significant healthcare costs in the developed world. However, there is no pharmacologic treatment to rapidly reverse mitochondrial deficits in the elderly. Here, we demonstrate that a single treatment with the mitochondrial-targeted peptide SS-31 restores in vivo mitochondrial energetics to young levels in aged mice after only one hour. Young (5 month old) and old (27 month old) mice were injected intraperitoneally with either saline or 3 mg kg-1 of SS-31. Skeletal muscle mitochondrial energetics were measured in vivo one hour after injection using a unique combination of optical and 31P magnetic resonance spectroscopy. Age-related declines in resting and maximal mitochondrial ATP production, coupling of oxidative phosphorylation (P/O), and cell energy state (PCr/ATP) were rapidly reversed after SS-31 treatment, while SS-31 had no observable effect on young muscle. These effects of SS-31 on mitochondrial energetics in aged muscle were also associated with a more reduced glutathione redox status and lower mitochondrial H2O2 emission. Skeletal muscle of aged mice was more fatigue resistant in situ one hour after SS-31 treatment, and eight days of SS-31 treatment led to increased whole-animal endurance capacity. These data demonstrate that SS-31 represents a new strategy for reversing age-related deficits in skeletal muscle with potential for translation into human use.",
keywords = "Aging, Mitochondria, Oxidative stress, Sarcopenia, Skeletal muscle",
author = "Siegel, {Michael P.} and Kruse, {Shane E.} and Justin Percival and Jorming Goh and White, {Collin C.} and Hopkins, {Heather C.} and Kavanagh, {Terrance J.} and Szeto, {Hazel H.} and Rabinovitch, {Peter S.} and Marcinek, {David J.}",
year = "2013",
month = "10",
day = "1",
doi = "10.1111/acel.12102",
language = "English",
volume = "12",
pages = "763--771",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice

AU - Siegel, Michael P.

AU - Kruse, Shane E.

AU - Percival, Justin

AU - Goh, Jorming

AU - White, Collin C.

AU - Hopkins, Heather C.

AU - Kavanagh, Terrance J.

AU - Szeto, Hazel H.

AU - Rabinovitch, Peter S.

AU - Marcinek, David J.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Mitochondrial dysfunction plays a key pathogenic role in aging skeletal muscle resulting in significant healthcare costs in the developed world. However, there is no pharmacologic treatment to rapidly reverse mitochondrial deficits in the elderly. Here, we demonstrate that a single treatment with the mitochondrial-targeted peptide SS-31 restores in vivo mitochondrial energetics to young levels in aged mice after only one hour. Young (5 month old) and old (27 month old) mice were injected intraperitoneally with either saline or 3 mg kg-1 of SS-31. Skeletal muscle mitochondrial energetics were measured in vivo one hour after injection using a unique combination of optical and 31P magnetic resonance spectroscopy. Age-related declines in resting and maximal mitochondrial ATP production, coupling of oxidative phosphorylation (P/O), and cell energy state (PCr/ATP) were rapidly reversed after SS-31 treatment, while SS-31 had no observable effect on young muscle. These effects of SS-31 on mitochondrial energetics in aged muscle were also associated with a more reduced glutathione redox status and lower mitochondrial H2O2 emission. Skeletal muscle of aged mice was more fatigue resistant in situ one hour after SS-31 treatment, and eight days of SS-31 treatment led to increased whole-animal endurance capacity. These data demonstrate that SS-31 represents a new strategy for reversing age-related deficits in skeletal muscle with potential for translation into human use.

AB - Mitochondrial dysfunction plays a key pathogenic role in aging skeletal muscle resulting in significant healthcare costs in the developed world. However, there is no pharmacologic treatment to rapidly reverse mitochondrial deficits in the elderly. Here, we demonstrate that a single treatment with the mitochondrial-targeted peptide SS-31 restores in vivo mitochondrial energetics to young levels in aged mice after only one hour. Young (5 month old) and old (27 month old) mice were injected intraperitoneally with either saline or 3 mg kg-1 of SS-31. Skeletal muscle mitochondrial energetics were measured in vivo one hour after injection using a unique combination of optical and 31P magnetic resonance spectroscopy. Age-related declines in resting and maximal mitochondrial ATP production, coupling of oxidative phosphorylation (P/O), and cell energy state (PCr/ATP) were rapidly reversed after SS-31 treatment, while SS-31 had no observable effect on young muscle. These effects of SS-31 on mitochondrial energetics in aged muscle were also associated with a more reduced glutathione redox status and lower mitochondrial H2O2 emission. Skeletal muscle of aged mice was more fatigue resistant in situ one hour after SS-31 treatment, and eight days of SS-31 treatment led to increased whole-animal endurance capacity. These data demonstrate that SS-31 represents a new strategy for reversing age-related deficits in skeletal muscle with potential for translation into human use.

KW - Aging

KW - Mitochondria

KW - Oxidative stress

KW - Sarcopenia

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=84883807865&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883807865&partnerID=8YFLogxK

U2 - 10.1111/acel.12102

DO - 10.1111/acel.12102

M3 - Article

VL - 12

SP - 763

EP - 771

JO - Aging Cell

JF - Aging Cell

SN - 1474-9718

IS - 5

ER -