Skeletal muscle ATP kinetics are impaired in frail mice

Ashwin Akki, Huanle Yang, Ashish Gupta, Vadappuram P Chacko, Toshiyuki Yano, Michelle K. Leppo, Charles Steenbergen, Jeremy Walston, Robert G. Weiss

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


The interleukin-10 knockout mouse (IL10tm/tm) has been proposed as a model for human frailty, a geriatric syndrome characterized by skeletal muscle (SM) weakness, because it develops an age-related decline in SM strength compared to control (C57BL/6J) mice. Compromised energy metabolism and energy deprivation appear to play a central role in muscle weakness in metabolic myopathies and muscular dystrophies. Nonetheless, it is not known whether SM energy metabolism is altered in frailty. A combination of in vivo 31P nuclear magnetic resonance experiments and biochemical assays was used to measure high-energy phosphate concentrations, the rate of ATP synthesis via creatine kinase (CK), the primary energy reserve reaction in SM, as well as the unidirectional rates of ATP synthesis from inorganic phosphate (Pi) in hind limb SM of 92-week-old control (n=7) and IL10tm/tm (n=6) mice. SM Phosphocreatine (20.2±2.3 vs. 16.8± 2.3 μmol/g, control vs. IL10tm/tm, p<0.05), ATP flux via CK (5.0±0.9 vs. 3.1±1.1 μmol/g/s, p<0.01), ATP synthesis from inorganic phosphate (Pi → ATP) (0.58±0.3 vs. 0.26±0.2 μmol/g/s, p<0.05) and the free energy released from ATP hydrolysis (ΔG∼ATP) were significantly lower and [Pi] (2.8±1.0 vs. 5.3±2.0 μmol/g, control vs. IL10tm/tm, p<0.05) markedly higher in IL10tm/tm than in control mice. These observations demonstrate that, despite normal in vitro metabolic enzyme activities, in vivo SM ATP kinetics, high-energy phosphate levels and energy release from ATP hydrolysis are reduced and inorganic phosphate is elevated in a murine model of frailty. These observations do not prove, but are consistent with the premise, that energetic abnormalities may contribute metabolically to SM weakness in this geriatric syndrome.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
Issue number1
StatePublished - Feb 2014


  • ATP
  • Creatine kinase
  • Frailty
  • Metabolism
  • Skeletal muscle

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology


Dive into the research topics of 'Skeletal muscle ATP kinetics are impaired in frail mice'. Together they form a unique fingerprint.

Cite this