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Sarcopenia, the age-related decline in muscle mass and function, is a significant contributor to increased frailty and mortality in the elderly. Currently, no FDA-approved treatment exists for sarcopenia. Here, we identified norharmane (NR), a β-carboline alkaloid, as a potential therapeutic agent for mitigating muscle aging. We aimed to determine the ability of NR to delay muscle aging in Caenorhabditis elegans (C. elegans), mouse, and muscle cells in mice and humans. NR treatment improved swimming ability and increased the maximum velocity in aged C. elegans. Transcriptomic analysis revealed that NR upregulated detoxification genes in C. elegans, including cytochrome P450, UGT, and GST enzymes. NR-induced benefits were dependent on the SKN-1/Nrf2 stress response pathway. In mammalian models, NR delayed cellular senescence in human skeletal muscle myoblasts and enhanced myogenesis in C2C12 cells and primary aged myoblasts. NR supplementation in aged mice prevented muscle loss, improved muscle function, and reduced markers of cellular senescence. We found that the p38 MAPK pathway mediated NR activation of Nrf2 by disrupting the Nrf2-Keap1 interaction. NR also improved oxygen consumption rates and promoted mitochondrial biogenesis. These findings suggest that NR is a promising candidate for preventing sarcopenia and improving muscle health.

Abstract: Stress and HIV disproportionately affect Latinx adults in the United States, contributing to numerous health inequities. Among people living with HIV (PLWH), increased stress is associated with decreased medication adherence, effectiveness, and higher rates of immunosuppression and comorbidities. Our study ( N = 126) examined the relationship between perceived stress and HIV-related health among Latinx ( n = 83) and non-Latinx White ( n = 43) PLWH. Latinx PLWH reported better HIV-related health outcomes than non-Latinx White PLWH, despite higher viral load (all p 's < .05). An interaction effect showed that higher perceived distress was associated with worse health outcomes and lower CD4+ T cell count only in Latinx PLWH ( p 's < .05). Our findings highlight the consequences of stress on HIV-related health. Notably, higher stress may be especially detrimental among Latinx PLWH, underscoring the need for more culturally tailored interventions in HIV-related care. Future research should include additional sociocultural factors and longitudinal assessment in a larger sample., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Association of Nurses in AIDS Care.)