Senotherapeutics in Bone Diseases

Aging is characterized by the disruption of physiological functioning of the body and has become a major risk factor for various chronic illnesses, including loss of bone and cartilage health. Cellular senescence occurs as a response to various stressors generated during the aging process, including telomere shortening, DNA damage, oxidative stress and genomic instability. Accumulation of senescent cells leads to the formation of senescence-associated secretory proteins and causes apoptotic resistance. Senescence also plays a significant role in the development of age-related joint dysfunction and bone diseases such as osteoarthritis and osteoporosis. Thus, to attenuate age-related bone disorders, “senotherapeutics” are undergoing extensive investigations as they directly eliminate the senescent bone and chondrocyte cells and help in bone tissue regeneration. Senotherapeutics include pharmacological interventions that exhibit a multitude of mechanisms of action and are classified as senolytics (dasatinib, quercetin, navitoclax), senomorphics (rapamycin, metformin, resveratrol) and senescence pathway inhibitors (JAK/STAT inhibitors). In this chapter, we explore the progress in the understanding of senotherapeutics and their pivotal role in the prevention and treatment of various bone and joint disorders.