Weakness, SR function and stress in gastrocnemius muscles of aged male rats

Exp Gerontol. 2014 Feb;50:40-4. doi: 10.1016/j.exger.2013.11.018. Epub 2013 Dec 4.


Aging is associated with a decline in muscle force that exceeds loss of muscle mass, suggesting that factors other than sarcopenia affect age-related muscle weakness. Here, we investigate in situ muscle force and sarcoplasmic reticulum (SR) properties in gastrocnemius muscles of adult (6-8 months) and aged (24 months) rats. Despite minimal loss of muscle mass, peak tetanic force was significantly reduced (-28%) in aged muscles. Adjusting for differences in muscle cross-sectional area mitigated the age difference (-23%), but it remained significant. The SR calcium release function was also impaired (-17%) with aging, although calcium uptake was not, and SR-associated glycogen increased (+30%) with aging. Western blotting revealed age related increases in Grp78, serinepalmitoyltransferase and neutral sphingomyelinase, suggesting that age increased the stress response and ceramide metabolism in the SR. In contrast Parkin, a protein associated with autophagic signaling, was reduced in the aged SR. These findings are consistent with a hypothesis that age-related impairments of the SR, possibly due to impaired autophagy and/or altered membrane metabolism, contribute to age-related muscle weakness, independent of changes in muscle mass.

Keywords: 78kD glucose regulated protein; Autophagy; CSA; Calcium; Ceramide; ER; E–C coupling; GP; Grp78; MHC; Parkin; SPT; SR; Sarcopenia; aSMase; acid sphingomyelinase; cross-sectional area; endoplasmic reticulum; excitation–contraction coupling; glycogen phosphorylase; l(o); myosin heavy chain; nSMase; neutral sphingomyelinase; optimal length; sarcoplasmic reticulum; serine palmitoyltransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Aging / pathology
  • Aging / physiology*
  • Animals
  • Autophagy / physiology
  • Body Weight / physiology
  • Calcium / metabolism
  • Male
  • Muscle Contraction / physiology
  • Muscle Weakness / metabolism
  • Muscle Weakness / pathology
  • Muscle Weakness / physiopathology*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology*
  • Myosin Heavy Chains / metabolism
  • Organ Size / physiology
  • Rats
  • Rats, Inbred F344
  • Sarcoplasmic Reticulum / metabolism
  • Sarcoplasmic Reticulum / physiology*


  • Myosin Heavy Chains
  • Calcium