title: Mitochondrial metabolic failure in telomere attrition-provoked aging of bone marrow mesenchymal stem cells.
abstract: The proliferation and differentiation potential of bone marrow mesenchymal stem cells (BMMSCs) declines with age and with in vitro passages. However, the underlying mechanisms and putative approaches to maintain their function are not fully understood. Recent studies have revealed telomere attrition as the core initiator determining functional decline in aging of BMMSCs. Telomere attrition activates downstream p53 signaling and compromises mitochondrial metabolism via the peroxisome proliferator-activated receptor gamma co-activator 1α/β (PGC-1α/β), a key process possesses peculiarities in BMMSCs distinct from other stem cells and their mature derivatives. Despite of the shortened telomere, the mitochondrial failure could be overcome through metabolic regulation by caloric restriction (CR) and its mediator Sirtuin 1 (SIRT1). Researches have shown that mitochondrial metabolic reprogramming by CR and SIRT1 alleviates functional decline of BMMSCs in aging. In this review, we intend to summarize our understanding about how telomere attrition initiates and induces mitochondrial compromise in functional decline of BMMSCs in aging, and the potential therapeutic strategies based on metabolic reprogramming.
authors.affiliation: Research and Development Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, Shaanxi, People's Republic of China.|State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Bingdong
authors.initials: B
authors.lastname: Sui
authors.affiliation: Research and Development Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, Shaanxi, People's Republic of China.|State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Chenghu
authors.initials: C
authors.lastname: Hu
authors.affiliation: Research and Development Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, Shaanxi, People's Republic of China. yanjin@fmmu.edu.cn.|State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China. yanjin@fmmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016922:Cellular Senescence / Q000235:genetics*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008928:Mitochondria / Q000378:metabolism*; D016615:Telomere
keywords: Caloric restriction; Mesenchymal stem cell aging; Mitochondrial metabolism; SIRT1; Telomere attrition