Stress and telomere shortening: Insights from cellular mechanisms

Lin, Jue; Epel, Elissa S.

doi:10.1016/j.arr.2021.101507

Cited by 207 publications

(169 citation statements)

References 188 publications

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“…Noteworthy, chronic stress is a central player impacting human health and aging and is linked to the development of many diseases [ 1 , 2 ]. With regards to oocyte aging, a better understanding of the pathways by which chronic stress affects the oocyte developmental competence in women of advanced age is important to counteract this process and to develop novel therapeutic strategies [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

The Interplay between Telomeres, Mitochondria, and Chronic Stress Exposure in the Aging Egg

Derevyanko

Skowrońska

Skowroński

et al. 2022

Cells

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While at the organismal level, biological aging can be estimated by telomere length and DNA methylation signatures, reliable biomarkers that can predict reproductive age are much needed to gauge the quality of an oocyte. Reproductive medicine and fertility centers often merely quantitate the ovarian reserve to predict the likelihood of fertilization and pregnancy in women of advanced reproductive age. It is highly important to address the level of age-related decline in oocyte quality since it leads to an increased risk of miscarriages and aneuploidy. Conversely, the pathways behind oocyte aging remain, in large part, elusive. Telomere shortening upon chronic stress exposure regulates mitochondria function and biogenesis by various pathways; therefore, establishing a link between these two important players and extrapolating them for the aging of oocytes will be the purpose of our commentary.

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Section: Introductionmentioning

confidence: 99%

The Interplay between Telomeres, Mitochondria, and Chronic Stress Exposure in the Aging Egg

Derevyanko

Skowrońska

Skowroński

et al. 2022

Cells

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“…Genetic and environmental factors may be integrated in human germ cells to shape both the epigenetic state of telomeres and telomere length for chromosomes that are transmitted to future generations. If a heritable epigenetic state can occur at human telomeres, as observed for C. elegans, and if this state can be demonstrated to be relevant to human physiology [198], it is possible that telomere-specific epigenetic interventions could be developed to affect specific tissues or to reprogram human germ cells.…”

Section: Future Directionsmentioning

confidence: 99%

Genetic and Epigenetic Inheritance at Telomeres

et al. 2022

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Transgenerational inheritance can occur at telomeres in distinct contexts. Deficiency for telomerase or telomere-binding proteins in germ cells can result in shortened or lengthened chromosome termini that are transmitted to progeny. In human families, altered telomere lengths can result in stem cell dysfunction or tumor development. Genetic inheritance of altered telomeres as well as mutations that alter telomeres can result in progressive telomere length changes over multiple generations. Telomeres of yeast can modulate the epigenetic state of subtelomeric genes in a manner that is mitotically heritable, and the effects of telomeres on subtelomeric gene expression may be relevant to senescence or other human adult-onset disorders. Recently, two novel epigenetic states were shown to occur at C. elegans telomeres, where very low or high levels of telomeric protein foci can be inherited for multiple generations through a process that is regulated by histone methylation.Together, these observations illustrate that information relevant to telomere biology can be inherited via genetic and epigenetic mechanisms, although the broad impact of epigenetic inheritance to human biology remains unclear.

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“…A final factor that makes propranolol an intriguing drug candidate is that it may have indirect effects on telomere attrition and accelerated aging. Stress has a negative impact on telomere maintenance, with evidence from a range of sources indicating that increased psychosocial stress is associated with telomere attrition, a process exacerbated by a positive feedback loop between psychological stress and reactive oxygen species, inflammation and mitochondrial dysfunction [ 150 , 151 ]. Propranolol has been shown to attenuate these biological downstream effects of psychosocial stress in healthy young adults [ 152 ].…”

Section: Drugging the Undruggablementioning

confidence: 99%

Inhibiting the Priming for Cancer in Li-Fraumeni Syndrome

Pantziarka

Blagden

2022

Cancers

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The concept of the pre-cancerous niche applies the ‘seed and soil’ theory of metastasis to the initial process of carcinogenesis. TP53 is at the nexus of this process and, in the context of Li-Fraumeni Syndrome (LFS), is a key determinant of the conditions in which cancers are formed and progress. Important factors in the creation of the pre-cancerous niche include disrupted tissue homeostasis, cellular metabolism and chronic inflammation. While druggability of TP53 remains a challenge, there is evidence that drug re-purposing may be able to address aspects of pre-cancerous niche formation and thereby reduce the risk of cancer in individuals with LFS.

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Stress and telomere shortening: Insights from cellular mechanisms

Cited by 207 publications

References 188 publications

The Interplay between Telomeres, Mitochondria, and Chronic Stress Exposure in the Aging Egg

The Interplay between Telomeres, Mitochondria, and Chronic Stress Exposure in the Aging Egg

Genetic and Epigenetic Inheritance at Telomeres

Inhibiting the Priming for Cancer in Li-Fraumeni Syndrome

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