title: Weakness, SR function and stress in gastrocnemius muscles of aged male rats.
abstract: 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.
authors: Division of Physical Therapy, Ohio University, Athens, OH, USA; Ohio Musculoskeletal and Neurological Institute (OMNI), Heritage College of Osteopathic Medicine, Athens, OH, USA. Electronic address: russd@ohio.edu.
authors: David W
authors: DW
authors: Russ
authors: Division of Physical Therapy, Ohio University, Athens, OH, USA.
authors: Allison M
authors: AM
authors: Wills
authors: Division of Physical Therapy, Ohio University, Athens, OH, USA.
authors: Iva M
authors: IM
authors: Boyd
authors: Division of Physical Therapy, Ohio University, Athens, OH, USA.
authors: Jodi
authors: J
authors: Krause
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018908:Muscle Weakness / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology*
chemical_list: D018995:Myosin Heavy Chains; D002118:Calcium
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