Cellular Senescence in Bone

Abstract

Senescence is an irreversible cell-cycle arrest process induced by environmental, genetic, and epigenetic factors. An accumulation of senescent cells in bone results in age-related disorders, and one of the common problems is osteoporosis. Deciphering the basic mechanisms contributing to the chronic ailments of aging may uncover new avenues for targeted treatment. This review focuses on the mechanisms and the most relevant research advancements in skeletal cellular senescence. To identify new options for the treatment or prevention of age-related chronic diseases, researchers have targeted hallmarks of aging, including telomere attrition, genomic instability, cellular senescence, and epigenetic alterations. First, this chapter provides an overview of the fundamentals of bone tissue, the causes of skeletal involution, and the role of cellular senescence in bone and bone diseases such as osteoporosis. Next, this review will discuss the utilization of pharmacological interventions in aging tissues and, more specifically, highlight the role of senescent cells to identify the most effective and safe strategies.

Bioanthropological and Biomechanical Perspectives on Skeletal Senescence Variation: A Literature Review

“…This is shown by the current studies, which decrease bone load strength due to aging correlation with cell senescence. 15,54 Senescent cells in bone tissues cause a higher rate of bone resorption than bone formation, which leads to lower bone mineral density. However, the occupied volume or space of the bone remains the same.…”

Telomere length as a predictive biomarker in osteoporosis (Review)

“…Based on experiments revealing a tight association between telomere shortening and the senescence of osteoblasts in vitro ( 43 , 44 ), a large population-based study was performed in a series of 2,150 female twins (aged 18-80 years), where the association between LTL and BMD was evaluated. A positive association between TL with BMD of the spine and distal forearm (but not with the femoral neck) was revealed, and longer telomeres were associated with a reduced risk of developing osteoporosis at two or more sites in women >50 years of age ( 16 ).…”

“…In particular, telomere shortening is strongly associated with a low BMD (13,52). The mechanism by which telomere shortening causes osteoporosis has come to light through experiments using mice or individuals harboring germline mutations in genes implicated in telomere maintenance (15,40,44,45,48,50,(52)(53)(54)(55)(56)(57)(58)(59). However, only a limited number of studies contradicted the positive association between telomere shortening and the aggravation of skeletal pathology (60)(61)(62)(63).…”