Regulatory mechanisms and clinical manifestations of musculoskeletal aging

Abstract

Aging is the strongest risk factor for degenerative bone and joint diseases. Clinical therapies for age-related musculoskeletal disorders face significant challenges as their pathogenic mechanisms remain largely unclear. This review article focuses on the recent advances in the understanding of regulatory mechanisms of musculoskeletal aging and their clinical relevance. We begin with the prevalence and socioeconomic impacts of major age-related musculoskeletal disorders such as sarcopenia, osteoporosis, osteoarthritis, and degenerative tendinopathy. The current understanding of responsible biological mechanisms involved in general aging is then summarized. Proposed molecular, cellular, and biomechanical mechanisms relevant to the clinical manifestations of aging in the musculoskeletal system are discussed in detail, with a focus on the disorders affecting muscle, bone, articular cartilage, and tendon. Although musculoskeletal aging processes share many common pathways with the aging of other body systems, unique molecular and cellular mechanisms may be involved in the aging processes of musculoskeletal tissues. Advancements in the understanding of regulatory mechanisms of musculoskeletal aging may promote the development of novel treatments for agerelated musculoskeletal disorders. Finally, future research directions for major musculoskeletal tissues including functional interaction between the tissues and their clinical relevance to age-related musculoskeletal disorders are highlighted in the Future Prospects section. ß

Epigenomic and transcriptional profiling identifies impaired glyoxylate detoxification in NAFLD as a risk factor for hyperoxaluria

“…In addi-tion to its dietary source, the endogenous Hyp pool derived from the turnover of body collagen contributes considerably to the daily excretion of oxalate (Knight et al, 2006;Li et al, 2016;Fargue et al, 2018). Therefore, aging (Grote et al, 2019;Laurent et al, 2019) and NAFLD-related perturbations of lean body mass (Lindströ m, 2007;Abrigo et al, 2016;Poggiogalle et al, 2017) likely influence the circulating concentration of endogenous Hyp and, consequently, oxalate excretion. This may be responsible for the differences observed between the mouse models and for the aging-dependent rise in hepatic oxalate release in lean mice in the absence of dietary Hyp.…”

An Inducible Model for Unraveling the Effects of Advanced Glycation End-Product Accumulation in Aging Connective Tissues

“…The population is aging at an unprecedented rate and understanding the link between aging and tissue degeneration could have major treatment and socioeconomic impacts [43]. Despite ample correlative evidence connecting AGEs to tissue injury [44,45], degeneration [23,26], and multiple chronic diseases, such as cardiovascular disease [17], chronic kidney disease [18], diabetes [46], Alzheimer's and Parkinson's disease [22], little is known how AGEs impact matrix mechanics and cell-matrix interactions, resulting in limited therapeutic options.…”

“…65 This increase in the amount of people living past age 65, suggests a better understanding of the link between aging and tissue degeneration could have major treatment and socioeconomic impacts. 66 Despite ample correlative evidence connecting AGEs to tissue injury, 63,67 degeneration, 24,27 and multiple chronic diseases, such as cardiovascular disease, 18 chronic kidney disease, 19 diabetes, 68 Alzheimer's and Parkinson's disease, 23 there are many un-answered questions related to AGEs impact on cellmatrix interactions, resulting in limited therapeutic options. One reason for this limited understanding is because AGEs are typically induced using concentrations of ribose greater than 200 mM, which decrease cell viability and make it impossible to investigate cell-matrix interactions.…”

Aging and age‐related diseases: from mechanisms to therapeutic strategies

“…The elderly are prone to injuries and degenerative musculoskeletal disorders. Sarcopenia and osteoarthritis (OA) are among the most common aging-related musculoskeletal disorders and have a significant economic impact (Grote et al 2019 ). Sarcopenia is defined as the loss of muscle mass and function with age.…”