Age Dependent Apoptosis and Loss of Rhabdosphincter Cells

Strasser, Hannes; Tiefenthaler, Martin; Steinlechner, Martin; Eder, Iris E.; Bartsch, Georg; Konwalinka, G

doi:10.1016/s0022-5347(05)67106-6

Cited by 134 publications

(66 citation statements)

References 22 publications

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“…We demonstrated that apoptotic DNA fragmentation increased progressively with age in the human gracilis muscle. These results are in accordance with those presented in the study by Strasser et al (37), who found an increased incidence of apoptosis using a TUNEL assay in human rhabdosphincter skeletal muscle with age. In addition, we have previously reported the age-dependent induction of AIF and a significant increase in DNA fragmentation in the human semitendinosus skeletal muscle (33).…”

Section: Discussionsupporting

confidence: 93%

Differential expression of apoptosis-related factors induces the age-related apoptosis of the gracilis muscle in humans

Park

Lee

Kim

et al. 2014

International Journal of Molecular Medicine

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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.

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Section: Discussionsupporting

confidence: 93%

Differential expression of apoptosis-related factors induces the age-related apoptosis of the gracilis muscle in humans

Park

Lee

Kim

et al. 2014

International Journal of Molecular Medicine

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“…The urethral sphincter muscle, which is the major muscle responsible for the urinary continent system, is composed of a thin inner layer of smooth muscle and a thick outer layer of striated muscle [24]. Apoptosis of the external rhabdosphincter cells is suggested as one of the major underlying causes of stress urinary incontinence [25]. Thus, although a large part of the low urinary tract symptoms, which are reduction in bladder capacity, uninhibited contractions, and diminished urethral pressure, are related to the aging-bladder itself [26], aging-related reduction of muscle changes can also affect the low urinary tract symptoms [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis of the external rhabdosphincter cells is suggested as one of the major underlying causes of stress urinary incontinence [25]. Thus, although a large part of the low urinary tract symptoms, which are reduction in bladder capacity, uninhibited contractions, and diminished urethral pressure, are related to the aging-bladder itself [26], aging-related reduction of muscle changes can also affect the low urinary tract symptoms [24,25]. Because proving the effect of exercise on the pelvic floor muscles or urethral rhabdosphincter muscle in animal models remains difficult, we analyzed the effect of an exercise regimen such as treadmill exercise on the gastrocnemius muscle which is most representative muscle in exercise related research in an old-age rat model to determine the effect of exercise on sarcopenia and the antiaging effect of pelvic floor muscle training.…”

Section: Discussionmentioning

confidence: 99%

Aerobic Exercise Affects Myostatin Expression in Aged Rat Skeletal Muscles: A Possibility of Antiaging Effects of Aerobic Exercise Related With Pelvic Floor Muscle and Urethral Rhabdosphincter

Jeong

Kim

et al. 2014

Int Neurourol J

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PurposeAging-induced loss of muscle mass and subsequent reduction of strength is a fundamental cause of frailty, functional decline, and disability. And this may lead to muscular dysfunction, voiding dysfunction, or urinary incontinence due to pelvic muscle weakness induced by aging. Physical exercise has been recommended for the prevention and the treatment of these age-related frail states. We investigated the effects of treadmill exercise on muscle strength, myostatin mRNA and protein expression, and gastrocnemius myocytes proliferation in aged rats to investigate the possible antiaging effects of aerobic exercise on skeletal muscles such as pelvic floor muscles and urethral rhabdosphincter muscle.MethodsIn this study, 5-month-old male Sprague-Dawley rats were used as the young-age group (n=20) and 24-month-old rats were used as the old-age group (n=20). Each group was randomly divided into two groups (n=10 in each group): the sedentary and the treadmill exercise group. The rats in the exercise groups were forced to run on a motorized treadmill for 30 minutes, once a day, for 6 weeks. For this study, a weight load test, hematoxylin and eosin staining, real-time and reverse transcription polymerase chain reaction for myostatin mRNA, myostatin western blot, and 5-bromo-2'-deoxyuridine immunohistochemistry were performed in the gastrocnemius muscle.ResultsThe age-induced reduction of muscle mass and strength was associated with a decrease in myocyte proliferation and an increase in myostatin mRNA and protein expression in the gastrocnemius. However, treadmill exercise improved muscle mass and strength through suppression of myostatin mRNA and protein expression, and myocyte proliferation increase in the gastrocnemius against the aging process.ConclusionsAerobic exercise is a useful strategy for enhancing muscle function against aging-induced loss of skeletal muscle mass and functions.

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“…Skeletal muscle atrophy and the loss of myofibers are associated with sarcopenia: a reduction of muscle mass and strength occurring during normal aging in rodents and humans (8,39). The rare reports on the incidence of apoptosis in muscles during normal aging did correlate sarcopenia and the loss of muscle cells with elevated DNA fragmentation in rats and humans (40,41). In this study, the course of apoptosis has been linked to the physiological age of the f ly by taking advantage of variations in longevity resulting from the genetic background.…”

Section: Discussionmentioning

confidence: 99%

Differential patterns of apoptosis in response to aging in Drosophila

Zheng

Edelman

Tharmarajah

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Several lines of evidence suggest that programmed cell death may play a role in the aging process and the age-related functional declines of multicellular organisms. To pave the way for the use of Drosophila to rigorously test this hypothesis in a genetic model organism, this work examines the pattern of apoptosis in the adult fly during aging. The analysis across the lifespan of caspase activity and DNA fragmentation shows that apoptosis occurs in adult flies at all ages and that it is linked to physiological age. The results establish that under normal conditions, fly aging is coupled with a lifelong gradual increase of apoptosis within muscle cells and an activation of apoptosis in fat cells of old flies. The nervous system does not show signs of apoptosis. These time-and tissue-specific changes indicate that aging influences the levels and the nature of the cells that commit to apoptosis. The comparison with the apoptotic response to starvation and oxidative stresses strongly suggests that the lifelong increase in flight and leg muscles results from the accumulation of oxidative damage associated with aging. This finding presents an attractive mechanism to account for the decline of locomotor functions and muscle loss in the elderly and opens the way for the genetic analysis of sarcopenia in Drosophila.oxidative stress

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Age Dependent Apoptosis and Loss of Rhabdosphincter Cells

Abstract: The dramatic decrease in the number of striated muscle cells in the rhabdosphincter of the elderly due to apoptosis represents the morphological basis for the high incidence of stress incontinence in this population.

Cited by 134 publications

References 22 publications

Differential expression of apoptosis-related factors induces the age-related apoptosis of the gracilis muscle in humans

Differential expression of apoptosis-related factors induces the age-related apoptosis of the gracilis muscle in humans

Aerobic Exercise Affects Myostatin Expression in Aged Rat Skeletal Muscles: A Possibility of Antiaging Effects of Aerobic Exercise Related With Pelvic Floor Muscle and Urethral Rhabdosphincter

Differential patterns of apoptosis in response to aging in Drosophila

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