Aug 2026· iScience· Vol 29· 0 citations· 38 references
Medicine
TL;DR
A gut bone inflammatory framework for exercise-associated skeletal protection in aging is supported by a D-galactose aging rat model and osteoblast-like cell experiments to examine exercise-associated changes in trimethylamine N-oxide (TMAO) and inflammasome signaling.
Abstract
Summary 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.
Aging and glycative stress are major, interrelated drivers of skeletal fragility, yet the extent to which they act through shared versus distinct biological pathways remains poorly defined, limiting integrated therapeutic strategies. This review compares the convergent and divergent mechanisms by which aging and glycat...
Salvador Peñarrubia, E. Martín-Guerrero, A. Gortázar et al.· Cells· 0 citations
Osteoporosis is a leading cause of age-related morbidity, yet existing antiresorptive and anabolic therapies remain limited by safety concerns, contraindications and poor long-term adherence. CADD522 is a small molecule inhibitor of the RUNX2 transcription factor currently under development for cancer therapy. Here, we...
A. Ersek, Myoung Sook Kim, Caterina M. Suelzu et al.· npj Drug Discovery· 0 citations
A structured research roadmap is proposed—centered on fate-mapping, lineage-specific depletion, and single-cell multi-omics—to convert the prevailing hypothesis into experimentally testable and clinically actionable evidence, while delineating the translational challenges that must be overcome to achieve precision seno...
Min-Shun Zhu, Jie Zhang, Hou-Shan Fang et al.· Frontiers in Endocrinology· 0 citations
Current evidence for inflammasome- and gasdermin-related pyroptotic signaling, HMGB1-associated damage signaling and their potential relevance to diabetic skeletal muscle are summarized and exercise is discussed as a modulator of upstream metabolic and inflammatory stress.
Peng-Yu Fu, Yuxuan Shi, Songbo Li et al.· Health and Metabolism· 0 citations
BACKGROUND AND PURPOSE
Senile osteoporosis presents a significant and growing health burden. Currently, no pharmacological agents are specifically approved for this condition. The dietary flavonoid naringenin (NAR) exhibits osteoprotective potential; however, its efficacy and direct molecular target in the context of s...
Chuanxin Sun, Yuke He, Fu Xiao et al.· British Journal of Pharmacol...· 0 citations
Osteoporotic fractures are traditionally regarded as severe clinical consequences of low bone mass and impaired bone strength, but fracture risk and repair outcomes are also shaped by systemic inflammation, intestinal barrier integrity, microbial metabolism, and osteoimmune regulation. Increasing evidence indicates tha...
Zi-Xin Xu, Shu-Tao Jin, Yi-Ze Liu et al.· Frontiers in Immunology· 0 citations
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