Cellular senescence and aging in bone

Published on Jan 1, 2021
· DOI :10.1016/B978-0-12-820071-1.00013-X
Manju Mohan1
Estimated H-index: 1
(University of Madras),
Sridhar Muthusami1
Estimated H-index: 1
(Karpagam University)
+ 3 AuthorsIlangovan Ramachandran11
Estimated H-index: 11
(University of Madras)
Abstract Cellular senescence is a hallmark of aging that is characterized by irreversible cell cycle arrest in response to various stress stimuli. It is a normal physiological event, which plays essential role in development, prevention of cancer, wound healing process, etc. Nevertheless, accumulation of senescent cells is the trigger and forms the basis of aging of a tissue/organ and, thus, the organismal aging. During aging, cells display a senescence-associated secretory phenotype (SASP) that transforms normal physiology into pathophysiology of a tissue/organ, leading to its dysfunction. Similarly, the accumulation of senescent bone cells and their dysfunction leads to skeletal morbidity. Therefore, factors regulating the process of cellular senescence during aging can serve as potential therapeutic targets to contain morbidity and improve the bone health. Extensive investigations are currently focused on deciphering age-related bone loss and diseases. In this chapter, authors systematically review the research findings and advancements available on cellular senescence and aging, to understand their contributions to the pathophysiology of bone and the therapeutic options to treat the aging bone.
📖 Papers frequently viewed together
4 Citations
42 Citations
10 Citations
#1Lei Qin (Southern University of Science and Technology)H-Index: 68
#2Wen Liu (Southern University of Science and Technology)H-Index: 1
Last. Guozhi Xiao (Southern University of Science and Technology)H-Index: 53
view all 4 authors...
Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and i...
39 CitationsSource
#1Maria Teresa Valenti (University of Verona)H-Index: 21
#2Luca Dalle Carbonare (University of Verona)H-Index: 24
Last. Monica Mottes (University of Verona)H-Index: 23
view all 4 authors...
Regular physical activity is essential for maintaining wellbeing; physical inactivity, on the contrary, is considered by the World Health Organization (WHO) as one of the most important risk factors for global mortality. During physical exercise different growth factors, cytokines and hormones are released, which affect positively the functions of heart, bone, brain and skeletal muscle. It has been reported that physical activity is able to stimulate tissue remodeling. Therefore, in this scenari...
6 CitationsSource
#1Abdul Qadir (NPU: Northwestern Polytechnical University)H-Index: 4
#2Shujing Liang (NPU: Northwestern Polytechnical University)H-Index: 3
Last. Airong Qian (NPU: Northwestern Polytechnical University)H-Index: 28
view all 6 authors...
Senile osteoporosis has become a worldwide bone disease with the aging of the world population. It increases the risk of bone fracture and seriously affects human health. Unlike postmenopausal osteoporosis which is linked to menopause in women, senile osteoporosis is due to aging, hence, affecting both men and women. It is commonly found in people with more than their 70s. Evidence has shown that with age increase, bone marrow stromal cells (BMSCs) differentiate into more adipocytes rather than ...
22 CitationsSource
#1Persefoni Fragkiadaki (UoC: University of Crete)H-Index: 15
#2Dragana Nikitovic (UoC: University of Crete)H-Index: 33
Last. Aristidis Tsatsakis (UoC: University of Crete)H-Index: 68
view all 10 authors...
Osteoarthritis (OA) and osteoporosis (OP) are associated skeletal pathologies and have as a distinct feature the abnormal reconstruction of the subchondral bone. OA and OP have been characterized as age-related diseases and have been associated with telomere shortening and altered telomerase activity (TA). This review discusses the role of telomeres and telomerase in OA and OP pathologies and focuses on the usability of telomere length (TL) and the rate of telomere shortening as potential diseas...
12 CitationsSource
#1Xing Yin (Sichuan University)H-Index: 4
#2Chenchen Zhou (Sichuan University)H-Index: 5
Last. Shujuan Zou (Sichuan University)H-Index: 19
view all 7 authors...
Autophagy is an evolutionarily conserved intracellular process, in which domestic cellular components are selectively digested for the recycling of nutrients and energy. This process is indispensable for cell homeostasis maintenance and stress responses. Both genetic and functional studies have demonstrated that multiple proteins involved in autophagic activities are critical to the survival, differentiation, and functioning of bone cells, including osteoblasts, osteocytes, and osteoclasts. Dysr...
34 CitationsSource
#1Xue-ling Liu (CAS: Chinese Academy of Sciences)H-Index: 5
#2Jia-li Liu (CAS: Chinese Academy of Sciences)H-Index: 4
Last. Linghua Meng (CAS: Chinese Academy of Sciences)H-Index: 29
view all 9 authors...
: The hotspot mutation H1047R in the oncogenic PIK3CA gene is frequently detected in breast cancer and enhances the enzymatic activity of PI3K to activate AKT/mTOR signaling cascade. Aberrant elevated PI3K activation has been reported to promote the tumorigenesis of breast cancer, but the mechanisms underlying are still needed to be elucidated. Here, we found that continuously activating PIK3CAH1047R conferred human mammary epithelial MCF-10A cells to cellular senescence upon serum-starvation. S...
4 CitationsSource
Abstract Transforming growth factor-beta1 (TGF-β1) is a pleiotropic and ubiquitous cytokine involved in bone development and bone remodeling. Matrix metalloproteinase-13 (MMP13) plays a role in the degradation of the extracellular matrix (ECM), and the regulation of this gene is critical in bone remodeling. We previously reported that TGF-β1 stimulates MMP13 expression in rat osteoblasts. Recently, studies have examined the regulation of bone metabolism by microRNAs (miRNAs) to determine their t...
4 CitationsSource
#1Joshua N. Farr (Mayo Clinic)H-Index: 28
#2Jennifer L. Rowsey (Mayo Clinic)H-Index: 3
Last. Sundeep Khosla (Mayo Clinic)H-Index: 130
view all 9 authors...
: Estrogen deficiency is a seminal mechanism in the pathogenesis of osteoporosis. Mounting evidence, however, establishes that cellular senescence, a fundamental mechanism that drives multiple age-related diseases, also causes osteoporosis. Recently, we systematically identified an accumulation of senescent cells, characterized by increased p16Ink4a and p21Cip1 levels and development of a senescence-associated secretory phenotype (SASP), in mouse bone/marrow and human bone with aging. We then de...
23 CitationsSource
#1Anne M. Josephson (NYU: New York University)H-Index: 4
#2Vivian Bradaschia-Correa (NYU: New York University)H-Index: 13
Last. Philipp Leucht (NYU: New York University)H-Index: 25
view all 15 authors...
Aging is associated with impaired tissue regeneration. Stem cell number and function have been identified as potential culprits. We first demonstrate a direct correlation between stem cell number and time to bone fracture union in a human patient cohort. We then devised an animal model recapitulating this age-associated decline in bone healing and identified increased cellular senescence caused by a systemic and local proinflammatory environment as the major contributor to the decline in skeleta...
41 CitationsSource
#1Vanessa D. Sherk (Anschutz Medical Campus)H-Index: 19
#2Clifford J. Rosen (Tufts University)H-Index: 125
Abstract Osteocytes are the most prevalent cell in the skeleton and are the master regulator of bone remodeling. Despite the understanding that osteocytes have a multiyear lifespan, and some factors induce apoptosis in osteocytes, much less is understood about the induction and consequences of osteocyte senescence. Filling these gaps in knowledge will provide novel approaches to slowing age-related bone loss and preventing fragility fractures. The purpose of this review is to examine the roles o...
13 CitationsSource
Cited By0