Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments

Abstract

Background: Osteoblast senescence is a central driverof age-related osteoporosis. Accumulating evidence shows that counteractingthis senescence can substantially mitigate bone loss. In this review, we summarize the hallmarks of osteoblast senescence, the signaling pathways involved, and therapeutic strategies that target osteoblast senescence tocombat age-related osteoporosis.

Methods: Chronic diseases associated with ageingpose a significant threat to human health. Studies have shown that osteoporosisis closely linked to the ageing process of the body and the senescence ofosteoblasts within the bone microenvironment. Counteracting the senescence ofosteoblasts and maintaining the balance of differentiation, proliferation andfunction between osteoclasts and osteoblasts has been a key focus in the research of age-related osteoporosis and bone loss. The biological behaviour andfunctionality of the osteoblast lineage related to senescence are modulated bya variety of targets, including signalling pathways, proteins and genes associated with ageing. This review aims to discuss the senescence-related characteristics of the osteoblast lineage, dissect the interplay and mechanisms between it and ageing-associated signalling pathways, proteinsand genes, as well as current strategies for the prevention and treatment ofosteoblast senescence.

Conclusion: This review systematically examines the regulatory interactions among markers, therapeutic targets, and signalingpathways associated with osteoblast senescence, alongside current potential strategies for targeting this process. It provides more comprehensive information for future research into the complex mechanisms underlying age-related osteoporosis driven by osteoblast senescence.

Keywords

ageing-related signalling pathways / anti-ageing strategies / bone microenvironment / osteoblast senescence / SASP

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.