Quantifying the Effects of Aging on Morphological and Cellular Properties of Human Female Pelvic Floor Muscles

Rieger, Mary; Duran, Pamela; Cook, Mark S.; Schenk, Simon; Shah, Manali; Jacobs, Marni; Christman, Karen L.; Kado, Deborah M.; Alperin, Marianna

doi:10.1007/s10439-021-02748-5

Cited by 13 publications

(9 citation statements)

References 51 publications

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“…Women older than 50 years represent the majority of patients presenting for management of clinically significant POP 4 . Aging is not a modifiable risk factor for POP and SUI; nevertheless, understanding discrete mechanisms may elucidate novel targets for treatment and preventive strategies 19,20 . It is imperative to expand our comprehension of the critical molecular pathways associated with aging as the number of older women suffering from POP and SUI is expected to continue to increase significantly 4,21 …”

Section: Methodsmentioning

confidence: 99%

“…4 Aging is not a modifiable risk factor for POP and SUI; nevertheless, understanding discrete mechanisms may elucidate novel targets for treatment and preventive strategies. 19,20 It is imperative to expand our comprehension of the critical molecular pathways associated with aging as the number of older women suffering from POP and SUI is expected to continue to increase significantly. 4,21 The mechanistic underpinnings of aging of cells and tissues and how these changes contribute to the pathogenesis of POP and SUI are detailed in the context of the hallmarks of aging.…”

Section: The Role Of Aging and Immunity In The Pathogenesis Of Pop An...mentioning

confidence: 99%

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Foundational Science and Mechanistic Insights for a Shared Disease Model: An Expert Consensus

Alperin¹,

Abramowitch²,

Alarab³

et al. 2022

Female Pelvic Med Reconstr Surg

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P elvic floor disorders (PFDs) are complex conditions that impact millions of women worldwide. It is estimated that PFDs will affect approximately 30%-50% of women older than 50 years and incur a 20% lifetime risk of undergoing at least 1 surgical procedure to repair either pelvic organ prolapse (POP) or stress urinary incontinence (SUI) by age 80 years. 1 The surgical costs alone are estimated to exceed $10 billion annually, 1-6 and this does not account for the cost of nonsurgical and conservative treatments. Although a large body of epidemiological literature provides important information regarding the risk factors for PFDs, the pathogenesis of POP and SUI continues to be poorly understood. Consequently, POP and SUI are associated with significant health care expenditure primarily due to lack of preventive measures, high failure rate of available interventions, and the need for retreatments.

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Section: Methodsmentioning

confidence: 99%

Section: The Role Of Aging and Immunity In The Pathogenesis Of Pop An...mentioning

confidence: 99%

Foundational Science and Mechanistic Insights for a Shared Disease Model: An Expert Consensus

Alperin¹,

Abramowitch²,

Alarab³

et al. 2022

Female Pelvic Med Reconstr Surg

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“…MuSCs in aged or diseased conditions have also been shown to become senescent and negatively affect skeletal muscle homeostasis and regeneration (Childs et al, 2015; García-Prat et al, 2016; He and Sharpless, 2017; Sacco et al, 2010; Sousa-Victor et al, 2014). To date, almost nothing is known about the effects of cellular senescence and aging on the female PFMs (Rieger et al, 2021). In the future, the irradiation model used in this study could be used as a tool to induce cellular senescence and premature PFM aging to further the knowledge in the field of female pelvic medicine.…”

Section: Discussionmentioning

confidence: 99%

The role of muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury

Sesillo

Rajesh

Wong

et al. 2021

Preprint

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Pelvic floor muscle (PFM) injury during childbirth is a key risk factor for subsequent pelvic floor disorders that affect millions of women worldwide. Muscle stem cells (MuSCs) play a central role in the regeneration of injured skeletal muscles, where they activate, proliferate, and differentiate to assure myogenesis needed for muscle recovery. For robust regenerative function, MuSCs require the support of fibro-adipogenic progenitors (FAPs) and immune cells. To elucidate the role of MuSCs, FAPs, and immune infiltrate in female PFM regeneration, we used radiation to perturb the system and followed PFM recovery in a simulated birth injury (SBI) rat model. Non-irradiated and irradiated rats were euthanized at 3,7, 10, and 28 days after SBI; PFMs were harvested and prepared for immunohistochemistry. Cross sectional area (CSA) of all PFM myofibers 28 days after injury in irradiated animals was significantly lower relative to non-irradiated injured controls, indicating impairment of PFM recovery. Following SBI in non-irradiated animals, the number of MuSCs and FAPs expanded significantly at 7 and 3 days after injury, respectively; this expansion did not occur in irradiated animals at the same time points. CSA of embryonic myosin heavy chain (eMyHC, marker of newly regenerated myofibers) positive fibers was also significantly smaller following SBI in irradiated muscles compared to PFMs from non-irradiated injured controls at 7 days. Our results demonstrate that loss of function and decreased expansion of MuSCs and FAPs associated with irradiation results in impaired PFM recovery, signifying essential roles for MuSCs and FAPs in the regenerative process of female PFMs after birth injury. These findings can inform the identification of novel preventative and therapeutic targets and the development of new treatments for PFM dysfunction and associated pelvic floor disorders.

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“…degeneration after menopause. 3,4 With older age, women accumulate multiple long-term conditions and are more likely to experience polypharmacy and multimorbidity. 5 Polypharmacy is the concurrent use of at least 5 medications, whereas multimorbidity is the coexistence of at least 2 independent chronic medical conditions in a person.…”

Section: Why This Mattersmentioning

confidence: 99%

Polypharmacy and Multimorbidity in the Urogynecology Population and Their Effect on Pelvic Floor Symptoms

Zuo

Tellechea

Kohn

et al. 2022

UROGC

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ImportancePolypharmacy and multimorbidity are common in older adults but has not been well studied in the urogynecologic patient population.ObjectivesThe objective of this study was to determine the prevalence of polypharmacy and multimorbidity in a diverse outpatient urogynecologic population and to examine whether polypharmacy and/or multimorbidity were associated with lower urinary tract symptoms, pelvic organ prolapse, defecatory distress, and/or female sexual dysfunction.Study DesignThis is a secondary analysis of a dual-center cross-sectional study of new patients presenting for evaluation of pelvic floor disorders at 2 urban academic outpatient urogynecology clinics. Baseline demographics and clinical characteristics were obtained from the electronic medical record. Validated surveys were administered to determine severity of lower urinary tract symptoms (Overactive Bladder Validated 8-Question Screener, Urogenital Distress Inventory-6), pelvic floor dysfunction (Pelvic Organ Prolapse Distress Inventory-6, Colorectal-Anal Distress Inventory-8), and sexual dysfunction (6-item Female Sexual Function Index). Standard statistical techniques were used.ResultsOne hundred ninety-seven women with mean age 58.8 years (SD, 13.4 years) were included, and most were of minority race/ethnicity (Black, 34.0%; Hispanic, 21.8%). The majority of participants met criteria for polypharmacy (58.4%) and multimorbidity (85.8%), with a mean prescription number of 6.5 (SD, ± 4.9) and mean number of medical comorbidities of 4.9 (SD, ± 3.3). Polypharmacy and multimorbidity were significantly associated with higher CRADI-8 scores. Specifically, polypharmacy was associated with straining with bowel movements and painful stools, whereas multimorbidity was associated with incomplete emptying and fecal urgency. There was no significant association between polypharmacy and multimorbidity with urinary symptoms, prolapse, or sexual dysfunction.ConclusionsPolypharmacy and multimorbidity are common in the urogynecologic population. There is a relationship between greater defecatory distress and polypharmacy and multimorbidity.

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Quantifying the Effects of Aging on Morphological and Cellular Properties of Human Female Pelvic Floor Muscles

Cited by 13 publications

References 51 publications

Foundational Science and Mechanistic Insights for a Shared Disease Model: An Expert Consensus

Foundational Science and Mechanistic Insights for a Shared Disease Model: An Expert Consensus

The role of muscle stem cells and fibro-adipogenic progenitors in female pelvic floor muscle regeneration following birth injury

Polypharmacy and Multimorbidity in the Urogynecology Population and Their Effect on Pelvic Floor Symptoms

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