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Adult muscle stem cells (MuSCs) are known to replicate upon activation before differentiating and fusing to regenerate myofibers. It is unclear whether MuSC differentiation is intrinsically linked to cell division, which has implications for stem cell population maintenance. We use single-cell RNA-sequencing to identify transcriptionally diverse subpopulations of MuSCs after 5 days of a growth stimulus in adult muscle. Trajectory inference in combination with a novel mouse model for tracking MuSC-derived myonuclei and in vivo labeling of DNA replication revealed an MuSC population that exhibited division-independent differentiation and fusion. These findings demonstrate that in response to a growth stimulus in the presence of intact myofibers, MuSC division is not obligatory. [ABSTRACT FROM AUTHOR]

Over the past decade, a large number of discoveries have shown that interventions (genetic, pharmacological, and nutritional) increase the lifespan of invertebrates and laboratory rodents. Therefore, the possibility of developing antiaging interventions for humans has gone from a dream to a reality. However, it has also become apparent that we need more information than just lifespan to evaluate the translational potential of any proposed antiaging intervention to humans. Information is needed on how an intervention alters the "healthspan" of an animal, that is, how the physiological functions that change with age are altered. In this report, we describe the utility and the limitations of assays in mice currently available for measuring a wide range of physiological functions that potentially impact quality of life. We encourage investigators and reviewers alike to expect at minimum an overall assessment of health in several domains across several ages before an intervention is labeled as "increasing healthspan." In addition, it is important that investigators indicate any tests in which the treated group did worse or did not differ statistically from controls because overall health is a complex phenotype, and no intervention discovered to date improves every aspect of health. Finally, we strongly recommend that functional measurements be performed in both males and females so that sex differences in the rate of functional decline in different domains are taken into consideration. [ABSTRACT FROM AUTHOR]

Although sarcopenia, age-associated loss of muscle mass and strength, is neither accelerated nor exacerbated by depletion of muscle stem cells, satellite cells, we hypothesized that adaptation in sarcopenic muscle would be compromised. To test this hypothesis, we depleted satellite cells with tamoxifen treatment of Pax7(CreER)-DTA mice at 4 months of age, and 20 months later subjected the plantaris muscle to 2 weeks of mechanical overload. We found myofiber hypertrophy was impaired in aged mice regardless of satellite cell content. Even in the absence of growth, vehicle-treated mice mounted a regenerative response, not apparent in tamoxifen-treated mice. Further, myonuclear accretion occurred in the absence of growth, which was prevented by satellite cell depletion, demonstrating that myonuclear addition is insufficient to drive myofiber hypertrophy. Satellite cell depletion increased extracellular matrix content of aged muscle that was exacerbated by overload, potentially limiting myofiber growth. These results support the idea that satellite cells regulate the muscle environment, and that their loss during aging may contribute to fibrosis, particularly during periods of remodeling. Overload induced a fiber-type composition improvement, independent of satellite cells, suggesting that aged muscle is very responsive to exercise-induced enhancement in oxidative capacity, even with an impaired hypertrophic response. [ABSTRACT FROM AUTHOR]

Dramatic advances in understanding mechanisms of aging have recently been made in model systems. Interventions have been devised that successfully enhance survival. Major issues still in need of resolution include whether these interventions not only increase survival but also enhance function, delay frailty, and can be translated into clinical application. It seems there are basic biologic findings close to being ready for translation. However, a number of barriers exist to translating these findings into realistic clinical interventions. Steps and resources needed include measuring not only survival but also impact of interventions on age-related disability, frailty, and onset of disease in model systems; development of clinically relevant measures of disability, frailty, and disease for each animal model and genetically tractable animal models of frailty; training and career-long funding mechanisms for geriatricians in basic science research and for basic scientists in geriatric issues; translationally capable review and funding mechanisms; emphasis on studies of interventions that can be initiated in later life for preventing or reversing disability; genetic association studies in humans to identify new candidate genes and pathways that correlate with disability, frailty, and age-related disease onset as well as longevity; study of exposure to environmental agents or toxins early in life on survival, disability, frailty, and disease in later life. [ABSTRACT FROM AUTHOR]

We report an age-dependent increase in nonimmunohematopoietic cells (CD45neg) in regenerating muscle characterized by high stem-cell antigen (Sca-1) expression. In aged regenerating muscle, only 14% of these CD45neg Sca-1pos cells express MyoD, whereas 82% of CD45negSca-1pos cells are MyoDpos in young adult muscle. In vitro, CD45negMyoDnegSca-1pos cells overexpress fibrosis-promoting genes, potentially controlled by Wnt2. The cells are proliferative, nonmyogenic, and nonadipogenic, and arise in clonally derived myoblast cultures from aged mice. MyoDneg Sca-1pos nonmyogenic cells also emerge in C2C12 myoblast cultures at late passage. Both in vitro and in vivo studies suggest that MyoDnegSca-1pos cells from aged muscle are more susceptible to apoptosis than myoblasts, which may contribute to depletion of the satellite cell pool. Thus, with age, a subset of myoblasts takes on an altered phenotype, which is marked by high Sca-1 expression. These cells do not participate in muscle regeneration, and instead may contribute to muscle fibrosis in aged muscle. [ABSTRACT FROM AUTHOR]

The objective was to study the formation of acetic aldehyde in cutting fluids and its relation to irritation of mucous membranes and the skin. Acetic aldehyde and formaldehyde were analysed in two large cutting fluid systems in an engineering industry. Samples were taken 1–5 times a week during a year. Concentration of the cutting fluid, leakage oils, pH, bacteria, yeast and fungi were analysed weekly. The occurrence of mucous membrane irritation was registered through questionnaires to the exposed workers. About 50 persons were exposed to each of the cutting fluids. The concentration of the aldehydes varied with time and between the cutting fluids. None of the analysed parameters could explain the variable concentration of aldehydes. Mucous membrane irntation was much more common in one of the systems, e.g. the prevalence of irritation in the nose was about 30–40% in workers exposed to a cutting fluid, while the corresponding prevalence was less than 10% in workers exposed to another fluid. The occurrence of symptoms was slightly associated with the concentration of aldehydes and pH of the fluid varied more in the fluid that caused most symptoms. A few measurements of ammonia indicated a higher concentration of ammonia in the fluid that caused most symptoms. It is concluded that irritation of mucous membranes and the skin may vary considerably between different cutting fluids of similar composition and use but the causal factor could not be determined in this study, but a variable pH and an increased concentration of ammonia may be indicators in this context. The concentration of acetic aldehyde vary with time and between cutting fluids with similar composition. A high variability may be an indicator of less stable cutting fluids. Better markers for the surveillance.of cutting fluids needs to be developed as well as a health control programme. [ABSTRACT FROM PUBLISHER]

Examines two aspects of muscle cell phenotype that may be affected by aging, primary myoblast cultures as well as established myoblast cell lines. Information on satellite cell replicative potential, satellite cell gene expression and satellite cell differentiation; Total replicative capacity of individual myoblasts from different aged donors; Discussion of the usefulness of the two in vitro systems in addressing fundamental molecular mechanisms of muscle aging.