Osteoporosis and osteoarthritis are the most common age-related diseases of the musculoskeletal system. They are responsible for high level of healthcare use and are often associated with comorbidities. Mechanisms of ageing such as senescence, inflammation and autophagy are common drivers for both diseases and molecules targeting those mechanisms (geroprotectors) have potential to prevent both diseases and their co-morbidities. However, studies to test the efficacy of geroprotectors on bone and joints are scant. The limited studies available show promising results to prevent and reverse Osteoporosis-like disease. In contrast, the effects on the development of Osteoarthritis-like disease in ageing mice has been disappointing thus far. Here we review the literature and report novel data on the effect of geroprotectors for Osteoporosis and Osteoarthritis, we challenge the notion that extension of lifespan correlates with extension of healthspan in all tissues and we highlight the need for more thorough studies to test the effects of geroprotectors on skeletal health in ageing organisms.
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http://dx.doi.org/10.3389/fcell.2022.682045 | DOI Listing |
Sci Rep
August 2024
Department of Sports Medicine, The Sixth Affiliated Hospital of Shenzhen University, Shenzhen Nanshan People's Hospital, Shenzhen, 518052, China.
Senescence of skeletal muscle (SkM) has been a primary contributor to senior weakness and disability in recent years. The gradually declining SkM function associated with senescence has recently been connected to an imbalance between damage and repair. Macrophages (Mac) are involved in SkM aging, and different macrophage subgroups hold different biological functions.
View Article and Find Full Text PDFNat Med
September 2024
Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
Preclinical evidence demonstrates that senescent cells accumulate with aging and that senolytics delay multiple age-related morbidities, including bone loss. Thus, we conducted a phase 2 randomized controlled trial of intermittent administration of the senolytic combination dasatinib plus quercetin (D + Q) in postmenopausal women (n = 60 participants). The primary endpoint, percentage changes at 20 weeks in the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx), did not differ between groups (median (interquartile range), D + Q -4.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
April 2024
State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Biological aging profoundly impairs the homeostasis of the skeletal system. Cellular senescence, a hallmark of biological aging, plays an instrumental role in bone disease. The underlying mechanisms of cellular senescence, triggered by both intracellular and extracellular stimuli, are multifaceted and yet to be uncovered.
View Article and Find Full Text PDFGeroscience
June 2024
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
Oxidative stress is associated with tissue dysfunctions that can lead to reduced health. Prior work has shown that oxidative stress contributes to both muscle atrophy and cellular senescence, which is a hallmark of aging that may drive in muscle atrophy and muscle contractile dysfunction. The purpose of the study was to test the hypothesis that cellular senescence contributes to muscle atrophy or weakness.
View Article and Find Full Text PDFBMC Biol
December 2023
Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Physical activity and several pharmacological approaches individually combat age-associated conditions and extend healthy longevity in model systems. It is tantalizing to extrapolate that combining geroprotector drugs with exercise could extend healthy longevity beyond any individual treatment. However, the current dogma suggests that taking leading geroprotector drugs on the same day as exercise may limit several health benefits.
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