ArticleiScience2026
Exercise is associated with attenuated aging-related osteoporosis through TMAO alpha Klotho inflammasome signaling.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Age-related osteoporosis is shaped by disrupted bone remodeling, metabolic stress, and inflammation. We combined an exploratory clinical comparison in adults aged 65 years and older with a D-galactose aging rat model and osteoblast-like cell experiments to examine exercise-associated changes in trimethylamine N-oxide (TMAO) and inflammasome signaling. Higher habitual activity in older adults was associated with higher hip T scores, lower serum and fecal TMAO, reduced IL-18 and IL-1β, and a turnover profile favoring bone formation. In aged rats, exercise lowered circulating and femoral marrow TMAO, preserved trabecular architecture, improved maximal load, and restrained TXNIP NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling while maintaining alpha Klotho. In osteoblast-like cells, TMAO promoted senescence and inflammasome assembly, whereas pathway modulation reduced these effects. These data support a gut bone inflammatory framework for exercise-associated skeletal protection in aging.
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