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Aging is the prime risk factor for the broad-based development of diseases. Frailty is a phenotypical hallmark of aging and is often used to assess whether the predicted benefits of a therapy outweigh the risks for older patients. Senescent cells form as a consequence of unresolved molecular damage and persistently secrete molecules that can impair...

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... inhi- bition of senescence induction stimulates osteogenesis and prevents osteoporosis [51]. These observations indi- cate a causal role of senescence in disrupting the balance between bone formation and resorption, leading to oste- oporosis ( Figure 2). ...
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... muscle fibers show atrophy that is linked to an age-related increase in cellular senescence. Satellite cells lose proliferation capacity through senescence induction or the chronic presence of SASP factors such as IL-6. Thus, regeneration of damaged tissue is prevented. Additionally, ILosteoblast and osteoclast function [46], and SASP factors secreted by osteocytes, such as IL-1 and MMP13, increase osteoclast differentiation and thereby increase bone resorption to cause the age-related bone loss associ- ated with osteoporosis [47][48][49]. The conditioned medium of senescent cells can decrease osteoblast function in vitro and promote osteoclast activity [50]. Furthermore, inhi- bition of senescence induction stimulates osteogenesis and prevents osteoporosis [51]. These observations indi- cate a causal role of senescence in disrupting the balance between bone formation and resorption, leading to oste- oporosis ( Figure ...

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... Subsequent cellular senescence could limit the ability of SC to regenerate and maintain itself by the overexpression of p16 (INK4a), which is the primary inducer of cell cycle arrest in cellular senescence [65]. On the other hand, the SASP significantly contributes to sarcopenia via inflammaging, where the persistent levels of IL-6 harm muscle integrity and function, causing muscle degradation and atrophy [67]. Given the consequences of cellular senescence in muscle degeneration, it is necessary to find new therapeutical strategies to attenuate cellular senescence and its SASP. ...
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... 1 Sarcopenic muscles are characterized by a reduction in contractile tissue mass (motor unit and fibre loss, Type II fibre atrophy) and an infiltration of other cells types (fat and connective tissue), which reduces muscle quality relative to tissue mass. 2 Although there are a number of contributing factors associated with the sarcopenic phenotype, one purported contributory mechanism is the negative effects of cellular senescence. 3 Originally demonstrated following serial passaging of cultured skin fibroblasts, 4 senescence is a phenomenon whereby cells cease to divide. It is now recognized that senescence can occur in multiple tissues, can be induced by both ageing and different stressors, and is associated with distinctive phenotypic alterations. ...
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Abstract Background The age‐related loss of muscle mass and quality, sarcopenia, has many contributing factors, one of which may be cellular senescence, but this is not well defined in human skeletal muscle. Method Primary cells were isolated from biopsy samples of the vastus lateralis muscle from healthy adult males (n = 6, 22 ± 1 years), sorted (magnetic activated cell sorting) and chemically induced (doxorubicin, DOX, 0.2 μM) to a senescent state. This allowed the parallel and simultaneous investigation of the two main skeletal muscle‐derived cell types: satellite cell‐derived CD56+ve/desmin+ve myoblasts (muscle precursor cells) and CD56− ve/TE7+ve fibroblasts (at >95% purity). Both cell types were followed for up to 35 days post DOX treatment with a combination of quantitative immunocytochemistry and qRT‐PCR for senescent markers and senescence‐associated secretory phenotype (SASP) factors. Results Myoblasts and fibroblasts showed temporal and quantitative differences in many of the senescence markers studied. p16 protein expression increased across the time course (P
... it has been reported that HK2 can attenuate cellular senescence by maintaining carbohydrate hypermetabolism [16]. Cellular senescence promotes the age-related decline of the skeletal muscular system [17]. Conversely, it has been reported that HK2 activity is upregulated and oxidative phosphorylation is enhanced by 12-week resistance training in young men [18]. ...
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... A promising new intervention either alone or in combination with cell-based therapies is the use of senolytic drugs. The understanding of senescent cells and their tissue degrading SASP factors in promoting age-related musculoskeletal pathology is becoming quite clear [153,154]. Furthermore, targeting senescent cells either genetically (in preclinical models) or pharmacologically has proven very effective in mitigating symptoms of OA at the histological and radiographic level. Thus, translation into clinical studies is promising and underway. ...
Chapter
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... Despite physiologic changes in sleep-awake patterns and sleep architecture during the aging process, older adults suffer with the consequences of a constellation of problems related to sleep duration, difficulty in initiating and maintaining sleep, and sleep-disordered breathing (1). The presence of sleep disturbances may trigger several pathways such as sympathetic activation, metabolic disturbances, and pro-inflammatory status (2), some of which are also implicated in the genesis of sarcopenia (3). Recently defined as a muscle failure, sarcopenia is characterized by the combination of low muscle strength with low muscle mass or altered muscle quality (4), increasing the risk of mortality, hospitalization, falls, fractures, and disability (5). ...
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... Consequently, senescence has been attributed to depletion of osteoprogenitors (80), whereas clearance of senescent cells in bone prevents agerelated bone loss (81). Acquisition of a senescent phenotype also prevents muscle repair in response to injury, and promotes muscle wasting (82,83). ...
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... While satellite cell depletion throughout adulthood does not appear to influence the onset or progression of sarcopenia in mice, this does not rule out the possibility that senescent J o u r n a l P r e -p r o o f satellite cells may exacerbate skeletal muscle loss or dysfunction in the context of aging, disease, or injury (Fry et al., 2015). Indeed, Sousa-Victor and colleagues provided intriguing evidence that satellite cells are vulnerable to senescence, directly influencing their regenerative potential (Baar et al., 2018;Sousa-Victor et al., 2014). In this report, satellite cells isolated from very old mice (28-32 months) were transplanted into injured muscles of young hosts and were unable to repair the damaged muscle, indicating that the impairment in function in very old mice is intrinsic, as it is not reversed by exposure to a young milieu. ...
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... It is not clear what the exact pathophysiological mechanism is, but several explanations have been proposed. These include inflammation, oxidative damage, and insulin resistance [33,34]. The sex differences are attributed to both a relatively higher fat mass proportion in women while a relatively higher fat-free mass proportion in men [35]. ...
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... These cytokines not only impact muscle fiber remodeling but also the stem cell pool. For instance, chronic high levels of IL-6 and TNF-a decrease or even inhibit the proliferation of satellite cells, possibly through the activation of IL-6/STAT3/suppressor of cytokine signaling 3 (SOCS3) and TNF-a/NF-jB signaling cascades, and the inhibition of anabolic mediators (like Akt), abolishing the regenerative capacity of the skeletal muscle (Wåhlin-Larsson et al. 2014Snijders et al. 2015;Dalle et al. 2017;Baar et al. 2018). High IL-6 circulating levels have been associated with the physical decline that occurs in older adults (Schaap et al. 2009) and evidence points to a gradual increase of IL-6 levels during aging, reaching higher values when age is superior to 60 years (Wyczalkowska-Tomasik et al. 2016). ...
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... 3 Senescence is a well-documented component of age-related diseases, with accumulating evidence linking a senescence associated secretory phenotype (SASP) to chronic impairments in stem cell function and the attenuation of skeletal muscle regeneration during ageing. 4 Thus, understanding and targeting cellular senescence during skeletal muscle ageing could have implications for the monitoring and treatment of sarcopenia. ...
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Extracellular vesicles (EVs) hold value as accessible biomarkers for understanding cellular differentiation and related pathologies. Herein, EV biomarkers in models of skeletal muscle dormancy and differentiation have been comparatively profiled using Raman spectroscopy (RS). Significant variations in the biochemical fingerprint of EVs were detected, with an elevation in peaks associated with lipid and protein signatures during early myogenic differentiation (day 2). Principal component analysis revealed a clear separation between the spectra of EVs derived from myogenic and senescent cell types, with non-overlapping interquartile ranges and population median. Observations aligned with nanoparticle tracking data, highlighting a significant early reduction in EV concentration in senescent myoblast cultures as well as notable variations in EV morphology and diameter. As differentiation progressed physical and biochemical differences in the properties of EVs became less pronounced. This study demonstrates the applicability of RS as a high-resolution analytical method for profiling biochemical changes in EVs during early myogenesis.