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

作者：McMullen Colleen A^*; Ferry Amy L; Gamboa Jorge L; Andrade Francisco H; Dupont Versteegden Esther E

来源：Experimental Gerontology, 2009, 44(6-7): 420-425.

DOI：10.1016/j.exger.2009.03.006

• Extraocular muscles
• Aging
• Apoptosis
• Autophagy
• LC3

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 IIcell 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.

• 出版日期2009-7