Long-lived post-mitotic cell aging: is a telomere clock at play?

Burbano, Maria Sol Jacome; Gilson, Éric

doi:10.1016/j.mad.2020.111256

Cited by 16 publications

(10 citation statements)

References 110 publications

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“…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: 88%

Cellular Senescence in Brain Aging

Sikora

Bielak-Żmijewska

Dudkowska

et al. 2021

Front. Aging Neurosci.

134

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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.

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Section: Cellular Senescencementioning

confidence: 88%

Cellular Senescence in Brain Aging

Sikora

Bielak-Żmijewska

Dudkowska

et al. 2021

Front. Aging Neurosci.

134

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“…An increased production of ROS is also the cause of heat-induced bleaching in the wild suggesting a potential telomere dysfunction due to oxidative stress in heat-induced bleaching as what we observed in dark-induced bleaching. Since oxidative stress can be both the cause and the consequence of dysregulated telomeres (Jacome- Burbano and Gilson, 2020), bleaching could, through an increased oxidative environment, create a positive loop accelerating telomere dysfunction and favoring diseases. If oxidative stress is well documented to be a major cause of symbiosis breakdown due to an increase in photosynthetic activity (Lesser, 1997, Dias et al, 2019, the cause of the oxidative stress observed here after six months of darkness is not known.…”

Section: Discussionmentioning

confidence: 99%

Telomere dysfunction is associated to dark-induced coral bleaching in the reef coral Stylophora pistillata

Gilson

Rouan²,

Tambutté

et al. 2021

Preprint

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Telomere DNA length is a complex trait controlled both by multiple loci and environmental factors. Even though the use of telomere DNA length measurement, as a method of assessing stress accumulation and predicting how this will influence survival, is currently being studied in numerous human cohort studies, the importance of telomere length for stress response in ecological studies remains at its infancy. Here, we investigated the telomere changes occurring in the symbiotic coral Stylophora pistillata that has experienced a continuous darkness over six months. This stress condition led to the loss of its symbionts, as what is also observed when bleaching occurs in the field at a large-scale due to climate changes and anthropogenic activities, threatening the worldwide reef ecosystem. We found that the continuous darkness condition was associated with telomere DNA length shortening and a downregulation of the expression of the telomere-associated protein Pot2. These results pave the way for future studies on the role of telomere in coral stress response and the importance of telomere dysregulation in endangered coral species.

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“…Indeed, relatively young HIV patients show a similar degree of T cell telomere attrition as centenarians [ 26 ]. Although long-lived post-mitotic cells in non-proliferative tissues such as the brain, skeletal muscle, fat, and heart were not initially thought to be affected by the telomere clock, telomere shortening has been identified more recently in these tissues, which may be triggered by SASP from other cells [ 37 ]. Telomere attrition has also been proposed to contribute to both the timing of parturition and death through the onset of inflammation [ 38 ].…”

Section: Nature Of Somatic Cellular Clocks: Telomeric Clockmentioning

confidence: 99%

No Time to Age: Uncoupling Aging from Chronological Time

LaRocca¹,

Lee²,

West³

et al. 2021

Genes

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Multicellular life evolved from simple unicellular organisms that could replicate indefinitely, being essentially ageless. At this point, life split into two fundamentally different cell types: the immortal germline representing an unbroken lineage of cell division with no intrinsic endpoint and the mortal soma, which ages and dies. In this review, we describe the germline as clock-free and the soma as clock-bound and discuss aging with respect to three DNA-based cellular clocks (telomeric, DNA methylation, and transposable element). The ticking of these clocks corresponds to the stepwise progressive limitation of growth and regeneration of somatic cells that we term somatic restriction. Somatic restriction acts in opposition to strategies that ensure continued germline replication and regeneration. We thus consider the plasticity of aging as a process not fixed to the pace of chronological time but one that can speed up or slow down depending on the rate of intrinsic cellular clocks. We further describe how germline factor reprogramming might be used to slow the rate of aging and potentially reverse it by causing the clocks to tick backward. Therefore, reprogramming may eventually lead to therapeutic strategies to treat degenerative diseases by altering aging itself, the one condition common to us all.

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Long-lived post-mitotic cell aging: is a telomere clock at play?

Cited by 16 publications

References 110 publications

Cellular Senescence in Brain Aging

Cellular Senescence in Brain Aging

Telomere dysfunction is associated to dark-induced coral bleaching in the reef coral Stylophora pistillata

No Time to Age: Uncoupling Aging from Chronological Time

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