학술논문

Apoptotic Signaling by AIF in Human Skeletal Muscle during Aging
Document Type
Dissertation/ Thesis
Source
Subject
human skeletal muscle
gracilis
apoptosis
aging
apoptosis-inducing factor
Language
English
Abstract
A decline of skeletal muscle mass and function is associated with aging. Apoptosis has been implicated as a mechanism for the loss of muscle cells in normal aging and plays an important role in age-related muscle loss. Several signaling pathways involved in skeletal muscle apoptosis are currently under intense investigation, particularly the caspase-independent pathway. This study investigated age-related changes in the human gracilis muscle ranging from the age of 10?s to 50?s. The gracilis muscle (n = 8) showed a significant increase in muscle apoptotic changes with age using in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). The Bcl-2, Bax, apoptosis-inducing factor (AIF), caspase-3, and calpain-1 mRNA levels were determined by RT-PCR. Western blot analyses of AIF and caspase-3 in the human gracilis muscle were performed. The caspase-3 activity in the gracilis muscle tended to change with age, although the changes were not significant, while the increase in DNA nuclei of the 50?s age group (5.561 ? 0.82) was associated with a 10?30% elevation in the expression of AIF as observed with western blotting. The AIF mRNA levels were significantly elevated by 10?60% in gracilis tissues from older individuals. In addition, a double-labeling experiment with TUNEL staining and immunofluorescence showed the co-localization of nuclear AIF-positive and TUNEL labeling. This study suggests that apoptosis in gracilis skeletal muscle in the elderly is partly mediated via the degradation of AIF.