The role of telomeres and telomerase in the senescence of postmitotic cells

Pańczyszyn, Anna; Boniewska-Bernacka, Ewa; Goc, Anna

doi:10.1016/j.dnarep.2020.102956

Cited by 21 publications

(15 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the involvement of telomeres and telomerase in aging goes well-beyond telomere shortening and DNA damage. This is particularly interesting in the case of nondividing post-mitotic cells, what has been highlighted recently (Jacome Burbano and Gilson, 2020;Panczyszyn et al, 2020).…”

Section: Cellular Senescencementioning

confidence: 85%

Cellular Senescence in Brain Aging

Sikora

Bielak-Żmijewska

Dudkowska

et al. 2021

Front. Aging Neurosci.

161

115

View full text Add to dashboard Cite

Aging of the brain can manifest itself as a memory and cognitive decline, which has been shown to frequently coincide with changes in the structural plasticity of dendritic spines. Decreased number and maturity of spines in aged animals and humans, together with changes in synaptic transmission, may reflect aberrant neuronal plasticity directly associated with impaired brain functions. In extreme, a neurodegenerative disease, which completely devastates the basic functions of the brain, may develop. While cellular senescence in peripheral tissues has recently been linked to aging and a number of aging-related disorders, its involvement in brain aging is just beginning to be explored. However, accumulated evidence suggests that cell senescence may play a role in the aging of the brain, as it has been documented in other organs. Senescent cells stop dividing and shift their activity to strengthen the secretory function, which leads to the acquisition of the so called senescence-associated secretory phenotype (SASP). Senescent cells have also other characteristics, such as altered morphology and proteostasis, decreased propensity to undergo apoptosis, autophagy impairment, accumulation of lipid droplets, increased activity of senescence-associated-β-galactosidase (SA-β-gal), and epigenetic alterations, including DNA methylation, chromatin remodeling, and histone post-translational modifications that, in consequence, result in altered gene expression. Proliferation-competent glial cells can undergo senescence both in vitro and in vivo, and they likely participate in neuroinflammation, which is characteristic for the aging brain. However, apart from proliferation-competent glial cells, the brain consists of post-mitotic neurons. Interestingly, it has emerged recently, that non-proliferating neuronal cells present in the brain or cultivated in vitro can also have some hallmarks, including SASP, typical for senescent cells that ceased to divide. It has been documented that so called senolytics, which by definition, eliminate senescent cells, can improve cognitive ability in mice models. In this review, we ask questions about the role of senescent brain cells in brain plasticity and cognitive functions impairments and how senolytics can improve them. We will discuss whether neuronal plasticity, defined as morphological and functional changes at the level of neurons and dendritic spines, can be the hallmark of neuronal senescence susceptible to the effects of senolytics.

show abstract

Section: Cellular Senescencementioning

confidence: 85%

Cellular Senescence in Brain Aging

Sikora

Bielak-Żmijewska

Dudkowska

et al. 2021

Front. Aging Neurosci.

161

115

View full text Add to dashboard Cite

show abstract

“…( 60,88 ) Interestingly, postmitotic osteocytes, like muscle cells and neurons, may form shortened telomeres in a replication‐independent manner. ( 89 )…”

Section: Cellular Senescencementioning

confidence: 99%

“…(60,88) Interestingly, postmitotic osteocytes, like muscle cells and neurons, may form shortened telomeres in a replication-independent manner. (89) Werner syndrome (WS) and dyskeratosis congenita are two genetic diseases with features of premature aging exhibiting shortened telomeres and premature osteoporosis. A model of accelerated aging in mice targeting the WS helicase and telomerase recapitulates the low bone mass and age-related osteoporosis seen in affected individuals and further shows shortened osteoblast lifespan and impaired differentiation without impaired osteoclast differentiation.…”

Section: Telomere Dysfunctionmentioning

confidence: 99%

Bone Aging, Cellular Senescence, and Osteoporosis

2021

View full text Add to dashboard Cite

Changes in aging bone that lead to osteoporosis are mediated at multiple levels, including hormonal alterations, skeletal unloading, and accumulation of senescent cells. This pathological interplay is superimposed upon medical conditions, potentially bone‐wasting medications, modifiable and unmodifiable personal risk factors, and genetic predisposition that accelerate bone loss with aging. In this study, the focus is on bone hemostasis and its dysregulation with aging. The major physiological changes with aging in bone and the role of cellular senescence in contributing to age‐related osteoporosis are summarized. The aspects of bone aging are reviewed including remodeling deficits, uncoupling phenomena, inducers of cellular senescence related to bone aging, roles of the senescence‐associated secretory phenotype, radiation‐induced bone loss as a model for bone aging, and the accumulation of senescent cells in the bone microenvironment as a predominant mechanism for age‐related osteoporosis. The study also addresses the rationale and potential for therapeutic interventions based on the clearance of senescent cells or suppression of the senescence‐associated secretory phenotype. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

show abstract

“…In contrast to their involvement in these normal physiological processes, excessive accumulation and activity of senescent cells is also associated with many of the chronic diseases of aging, such as atherosclerosis, cancer, cardiac and kidney dysfunctions, neurodegeneration, pulmonary fibrosis, and many others (Campisi et al, 2019;Hou et al, 2019;Khosla et al, 2020;Lee and Schmitt, 2019). Moreover, recent studies have identified ''senescent-like'' signatures in post-mitotic cells such as cardiomyocytes, osteocytes, osteoclasts, adipocytes, and neurons (Pa nczyszyn et al, 2020). Interestingly, elimination of these cell types in aged and diseased mice is associated with improvements in health-span (Raffaele et al, 2020).…”

mentioning

confidence: 99%