Age-related changes of cell death pathways in rat extraocular muscle

Exp Gerontol. 2009 Jun-Jul;44(6-7):420-5. doi: 10.1016/j.exger.2009.03.006. Epub 2009 Mar 31.

Abstract

Changes in the structure and function of aging non-locomotor muscles remains understudied, despite their importance for daily living. Extraocular muscles (EOMs) have a high incidence of age-related mitochondrial defects possibly because of the metabolic stress resulting from their fast and constant activity. Apoptosis and autophagy (type I and II cell death, respectively) are linked to defects in mitochondrial function and contribute to sarcopenia in hind limb muscles. Therefore, we hypothesized that apoptosis and autophagy are altered with age in the EOMs. Muscles from 6-, 18-, and 30-month-old male Fisher 344-Brown Norway rats were used to investigate type I cell death, caspase-3, -8, -9, and -12 activity, and type II cell death. Apoptosis, as measured by TUNEL positive nuclei, and mono- and oligo-nucleosomal content, did not change with age. Similarly, caspase-3, -8, -9, and -12 activity was not affected by aging. By contrast, autophagy, as estimated by gene expression of Atg5 and Atg7, and protein abundance of LC3 was lower in EOMs of aged rats. Based on these data, we suggest that the decrease in autophagy with age leads to the accumulation of damaged organelles, particularly mitochondria, which results in the decrease in function observed in EOM with age.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / pathology*
  • Animals
  • Apoptosis / physiology*
  • Autophagy / physiology*
  • Caspase 3 / metabolism
  • Immunohistochemistry
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Oculomotor Muscles / metabolism
  • Oculomotor Muscles / pathology*
  • Rats
  • Rats, Inbred F344
  • Sarcopenia / pathology*

Substances

  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • Caspase 3