Urinary incontinence in the elderly and age-dependent apoptosis of rhabdosphincter cells

Strasser, Hannes; Tiefenthaler, Martin; Steinlechner, Martin; Bartsch, Georg; Konwalinka, G

doi:10.1016/s0140-6736(99)02588-x

Cited by 122 publications

(67 citation statements)

References 5 publications

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“…Although loss of anatomic support due to vaginal deliveries appears to play an important role in its development, other changes seen with aging also contribute to the development of an incompetent urethra. Such changes include atrophy of the skeletal rhabdosphincter, atrophy of the smooth muscle of the urethra, loss of neuronal mass, and hormonal changes seen with menopause (3,6,11,24,25). It has been clear that no single alteration but a combination of factors acting together cause SUI.…”

Section: Discussionmentioning

confidence: 99%

New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency

Rodríguez¹,

Chen²,

Jack³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Rodríguez, Larissa V., Shinhong Chen, Gregory S. Jack, Fernando de Almeida, Kyo Won Lee, and Rong Zhang. New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency. Am J Physiol Regul Integr Comp Physiol 288: R1332-R1338, 2005. First published January 13, 2005; doi:10.1152/ajpregu.00760.2004.-Existing animal models of stress urinary incontinence (SUI) are limited because of the low rate of incontinence seen in the animals and to their relatively low durability. In addition, most methods described to measure incontinence are operator-dependent. The aim of this study was to develop a new durable animal model of SUI and establish objective measures to quantify SUI. We subjected female rats to transabdominal urethrolysis. At baseline and at 1,4,8,12, and 24 wk after intervention, animals underwent cystometry and evaluation with abdominal leak point pressure (ALPP). Urethral resistance was evaluated by retrograde urethral perfusion pressure (RUPP). Tissues were obtained for histology and immunohistochemistry. Normal female rats had an average ALPP of 19.4 cmH2O and RUPP of 22.6 cmH2O at baseline. More than 93% of the animals had significantly decreased ALPP and RUPP after the procedure. The mean ALPP and RUPP decreased to 9.8 cmH2O and 11.2 cmH2O, respectively, by 1 wk after urethrolysis. These changes were maintained for up to 24 wk. Changes seen in urethral resistance and ALPP appear to be mediated by apoptosis, decreased neuronal mass, and smooth muscle atrophy. These results indicate that transabdominal urethrolysis is a reliable method of achieving durable decreased urethral resistance in a SUI model. RUPP and ALPP are objective and reproducible methods of assessing urethral resistance. Changes in continence and urethral resistance appear to be mediated by denervation and smooth muscle atrophy, which are seen in both elderly incontinent patients and in patients with intrinsic sphincter dysfunction. stress incontinence; abdominal leak point pressure; retrograde perfusion; urethral resistance URINARY INCONTINENCE AFFECTS 13 million Americans, the vast majority of whom (85%) are women. In 1995, the annual cost of incontinence in the United States was estimated to be $26.3 billion (26). This represents a 92% increase from the 1984 cost, and it is expected to increase due to the aging population (9). Approximately 50% of all incontinent women are classified as having stress incontinence (5, 8). The pathophysiology of stress urinary incontinence (SUI) is multifactorial and poorly understood but appears to be in part due to anatomic changes in urethral support and dysfunction of the intrinsic sphincteric mechanism of the urethra resulting in involuntary urine loss during any activity that causes abdominal straining. Given that the list of such activities includes everyday occurrences like coughing, laughing, and sneezing, SUI has an enormous impact on quality of life. In the elderly, other factors also appear to contribute to the development of an i...

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Section: Discussionmentioning

confidence: 99%

New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency

Rodríguez¹,

Chen²,

Jack³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…To date, only three reports have been published examining the occurrence of myocyte apoptosis in older persons [11,16,83]. However, none of these studies has examined either specific biochemical pathways of apoptosis or functional implications.…”

Section: The Involvement Of Myocyte Apoptosis In Human Sarcopeniamentioning

confidence: 99%

“…Over the past few years, evidence has accumulated suggesting that an accelerated elimination of myonuclei via an apoptosis-like process might play a significant role in the loss of muscle mass and function with age [11–20]. A key feature of apoptosis in skeletal muscle is linked to the multinucleated nature of myofibers, where single nuclei (and their portion of cytoplasm) can be eliminated without the dismantling of the whole fiber.…”

Section: Introductionmentioning

confidence: 99%

Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

Marzetti

Privitera

Simili

et al. 2010

The Scientific World JOURNAL

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Sarcopenia, the age-related decline in muscle mass and function, represents a significant health issue due to the high prevalence of frailty and disability associated with this condition. Nevertheless, the cellular mechanisms responsible for the loss of muscle mass in old age are still largely unknown. An altered regulation of myocyte apoptosis has recently emerged as a possible contributor to the pathogenesis of sarcopenia. Studies in animal models have shown that the severity of skeletal muscle apoptosis increases over the course of aging and correlates with the degree of muscle mass and strength decline. Several apoptotic pathways are operative in aged muscles, with the mitochondria- and TNF-α-mediated pathways likely being the most relevant to sarcopenia. However, despite the growing number of studies on the subject, a definite mechanistic link between myocyte apoptosis and age-related muscle atrophy has not yet been established. Furthermore, the evidence on the role played by apoptosis in human sarcopenia is still sparse. Clearly, further research is required to better define the involvement of myocyte apoptosis in the pathogenesis of muscle loss at advanced age. This knowledge will likely help in the design of more effective therapeutic strategies to preserve muscle mass into old age, thus fostering independence of the elderly population and reducing the socioeconomic burden associated with sarcopenia.

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“…(2011). In human muscle, increased levels of TUNEL‐positive nuclei have been detected from biopsies (Strasser et al ., 1999; Malmgren et al ., 2001; Whitman et al ., 2005). An increase in caspase‐3 levels was not detected (Whitman et al ., 2005).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis and necrosis mediate skeletal muscle fiber loss in age‐induced mitochondrial enzymatic abnormalities

et al. 2015

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SummarySarcopenia, the age‐induced loss of skeletal muscle mass and function, results from the contributions of both fiber atrophy and loss of myofibers. We have previously characterized sarcopenia in FBN rats, documenting age‐dependent declines in muscle mass and fiber number along with increased fiber atrophy and fibrosis in vastus lateralis and rectus femoris muscles. Concomitant with these sarcopenic changes is an increased abundance of mitochondrial DNA deletion mutations and electron transport chain (ETC) abnormalities. In this study, we used immunohistological and histochemical approaches to define cell death pathways involved in sarcopenia. Activation of muscle cell death pathways was age‐dependent with most apoptotic and necrotic muscle fibers exhibiting ETC abnormalities. Although activation of apoptosis was a prominent feature of electron transport abnormal muscle fibers, necrosis was predominant in atrophic and broken ETC‐abnormal fibers. These data suggest that mitochondrial dysfunction is a major contributor to the activation of cell death processes in aged muscle fibers. The link between ETC abnormalities, apoptosis, fiber atrophy, and necrosis supports the hypothesis that mitochondrial DNA deletion mutations are causal in myofiber loss. These studies suggest a progression of events beginning with the generation and accumulation of a mtDNA deletion mutation, the concomitant development of ETC abnormalities, a subsequent triggering of apoptotic and, ultimately, necrotic events resulting in muscle fiber atrophy, breakage, and fiber loss.

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Urinary incontinence in the elderly and age-dependent apoptosis of rhabdosphincter cells

Cited by 122 publications

References 5 publications

New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency

New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency

Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

Apoptosis and necrosis mediate skeletal muscle fiber loss in age‐induced mitochondrial enzymatic abnormalities

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