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

Colleen A. McMullen, Amy L. Ferry, Jorge L. Gamboa, Francisco H. Andrade, Esther E. Dupont-Versteegden

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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.

Original languageEnglish
Pages (from-to)420-425
Number of pages6
JournalExperimental Gerontology
Issue number6-7
StatePublished - Jun 2009

Bibliographical note

Funding Information:
The authors wish to thank Joey Bose and Tom Newcomb for technical assistance. This work was supported by National Institutes of Health grants DC007983 (to C. A. McMullen), EY12998 (to F.H. Andrade) and AG028925 (to E.E. Dupont-Versteegden).


  • Aging
  • Apoptosis
  • Autophagy
  • Extraocular muscles
  • LC3

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology


Dive into the research topics of 'Age-related changes of cell death pathways in rat extraocular muscle'. Together they form a unique fingerprint.

Cite this