title: [Osteoimmunologic regulation of aging].
abstract: In bones, aging manifests itself as a shift towards production of myeloid cells in bone marrow, a condition associated with increased chronic inflammation by macrophages and decreased bone mass due to excess bone resorption by osteoclasts. An increase in the ratio of RANKL, a cytokine promoting osteoclast differentiation, to osteoprotegerin (OPG) , which acts as a decoy RANKL receptor, cannot explain the observed increase in osteoclast production, as serum OPG levels increase with age in humans, apparently to levels insufficient to counteract bone loss and prevent fracture. Age-related increases in osteoclastogenesis, decreases in lymphopoiesis, and inflammation including arthritis are likely best explained by a vicious cycle of myeloid skewing and inflammation occurring in bone marrow. These activities are due to aging of both hematopoietic stem cells themselves and the bone marrow microenvironment (niche cells) , which supports hematopoiesis. Impaired osteoblastogenesis and niche cell function are most likely pathologies emerging from increased oxidative stress, peroxisome proliferator-activated receptorγ (PPARγ) activity, and adipogenesis in the aging bone marrow. Currently, administration of either OPG or an anti-RANKL antibody has proved beneficial to prevent block bone dysfunction and osteoporosis in the elderly. However, anti-aging interventions targeting mesenchymal stem cell differentiation in the bone marrow may also help counteract inflammation and osteoclastic bone loss and enhance osteoblastic bone formation.
authors.affiliation: School of Medicine, Keio University, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuo
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D001842:Bone and Bones / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D010010:Osteoclasts / Q000166:cytology / Q000276:immunology*; D053244:Osteoprotegerin / Q000276:immunology* / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand