title: Differential expression of apoptosis-related factors induces the age-related apoptosis of the gracilis muscle in humans.
abstract: In the normal aging process, apoptosis has been implicated as a mechanism responsible for the loss of muscle cells 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 the age-related apoptotic changes occurring in the gracilis muscle in humans between 10 and 50 years of age. For this purpose, muscle samples were divided into 5 groups (n=8). Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and immunofluorescence detection were performed to determine the number of apoptotic muscle cells in each group. In addition, the expression levels of apoptosis-related factors, such as Bcl-2, Bax, apoptosis-inducing factor (AIF), caspase-3 and calpain-1 were determined by RT-PCR and western blot analysis. TUNEL assay revealed a significant increase in gracilis muscle apoptosis with aging. The activity of caspase-3 in the gracilis muscle tended to change with age, although the changes were not significant, while the increase in DNA nuclei in muscle from 50 years of age (5.419±0.97) was associated with an increase in the expression of AIF, as observed both at protein (10-30%) and mRNA level (10-60%) in gracilis tissues. Taken together, our results demonstrated that the relative Bcl-2 expression decreased with aging, while Bax expression was upregulated compared to 10-year-olds. In addition, a double-labeling experiment with TUNEL staining and immunofluorescence revealed the co-localization of nuclear AIF-positive and TUNEL-labeled cells. This study suggests that apoptosis in gracilis skeletal muscle in the elderly is partly mediated through the expression of Bcl-2/Bax and the degradation of AIF.
authors.affiliation: Graduate School of Education, Yong In University, Seoul 130-701, Republic of Korea.
authors.forename: Soo Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Prescriptionology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Kyoung Ho
authors.initials: KH
authors.lastname: Yoon
authors.affiliation: Department of Prescriptionology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Seong Kyu
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Prescriptionology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Mun Seog
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3