Stochastic Mechanism of Cellular Aging—Abrupt Telomere Shortening as a Model for Stochastic Nature of Cellular Aging

1999 ◽  
Vol 197 (4) ◽  
pp. 425-438 ◽  
Author(s):  
Ivica Rubelj ◽  
Zoran Vondracek
Keyword(s):  
Cellular Aging ◽  
Telomere Shortening ◽  
Stochastic Nature ◽  
Stochastic Mechanism

scholarly journals Telomere Shortening and Accelerated Aging in US Military Veterans

2021 ◽  
Vol 18 (4) ◽  
pp. 1743
Author(s):  
Jeffrey T. Howard ◽  
Jud C. Janak ◽  
Alexis R. Santos-Lozada ◽  
Sarah McEvilla ◽  
Stephanie D. Ansley ◽  
...  
Keyword(s):  
Telomere Length ◽  
Military Service ◽  
Accelerated Aging ◽  
Cellular Aging ◽  
Veterans Health ◽  
Cvd Risk ◽  
Base Pairs ◽  
Telomere Shortening ◽  
Race Ethnicity ◽  
Service Data

A growing body of literature on military personnel and veterans’ health suggests that prior military service may be associated with exposures that increase the risk of cardiovascular disease (CVD), which may differ by race/ethnicity. This study examined the hypothesis that differential telomere shortening, a measure of cellular aging, by race/ethnicity may explain prior findings of differential CVD risk in racial/ethnic groups with military service. Data from the first two continuous waves of the National Health and Nutrition Examination Survey (NHANES), administered from 1999–2002 were analyzed. Mean telomere length in base pairs was analyzed with multivariable adjusted linear regression with complex sample design, stratified by sex. The unadjusted mean telomere length was 225.8 base shorter for individuals with prior military service. The mean telomere length for men was 47.2 (95% CI: −92.9, −1.5; p < 0.05) base pairs shorter for men with military service after adjustment for demographic, socioeconomic, and behavioral variables, but did not differ significantly in women with and without prior military service. The interaction between military service and race/ethnicity was not significant for men or women. The results suggest that military service may contribute to accelerated aging as a result of health damaging exposures, such as combat, injury, and environmental contaminants, though other unmeasured confounders could also potentially explain the results.

scholarly journals Early Life Stress, Frontoamygdala Connectivity, and Biological Aging in Adolescence: A Longitudinal Investigation

2020 ◽  
Vol 30 (7) ◽  
pp. 4269-4280 ◽  
Author(s):  
Jonas G Miller ◽  
Tiffany C Ho ◽  
Kathryn L Humphreys ◽  
Lucy S King ◽  
Lara C Foland-Ross ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Developmental Process ◽  
Early Life Stress ◽  
Neural Circuitry ◽  
Cellular Aging ◽  
Biological Aging ◽  
Telomere Shortening ◽  
Pubertal Tempo ◽  
Negative Coupling

Abstract Early life stress (ELS) may accelerate frontoamygdala development related to socioemotional processing, serving as a potential source of resilience. Whether this circuit is associated with other proposed measures of accelerated development is unknown. In a sample of young adolescents, we examined the relations among ELS, frontoamygdala circuitry during viewing of emotional faces, cellular aging as measured by telomere shortening, and pubertal tempo. We found that greater cumulative severity of ELS was associated with stronger negative coupling between bilateral centromedial amygdala and the ventromedial prefrontal cortex, a pattern that may reflect more mature connectivity. More negative frontoamygdala coupling (for distinct amygdala subdivisions) was associated with slower telomere shortening and pubertal tempo over 2 years. These potentially protective associations of negative frontoamygdala connectivity were most pronounced in adolescents who had been exposed to higher ELS. Our findings provide support for the formulation that ELS accelerates maturation of frontoamygdala connectivity and provide novel evidence that this neural circuitry confers protection against accelerated biological aging, particularly for adolescents who have experienced higher ELS. Although negative frontoamygdala connectivity may be an adaptation to ELS, frontoamygdala connectivity, cellular aging, and pubertal tempo do not appear to be measures of the same developmental process.

scholarly journals The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 169 ◽  
Author(s):  
Tomer Harpaz ◽  
Heba Abumock ◽  
Einat Beery ◽  
Yonatan Edel ◽  
Meir Lahav ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Methylation Status ◽  
Telomerase Activity ◽  
Cellular Aging ◽  
Human Foreskin Fibroblast ◽  
Telomere Shortening ◽  
Social Drinking ◽  
Carcinogenic Potential ◽  
Human Hepatocellular Carcinoma Cells ◽  
In Cells

Telomeres (TLs) protect chromosome ends from chromosomal fusion and degradation, thus conferring genomic stability, and play crucial roles in cellular aging and disease. Recent studies have found a correlation between environmental, physiological and even mental stresses on TL dynamics in humans. However, the causal relationship between stress and TL length and the molecular mechanisms underlying that relationship are far from being understood. This study describes the effect of moderate concentrations of ethanol, equivalent to social drinking, on human TL dynamics and partially elucidates the mechanism mediating this effect. The exposure of Immortalized human foreskin fibroblast, primary human foreskin fibroblast and human hepatocellular carcinoma cells to 25 mM ethanol for one week moderately shortened telomeres in all cells. Similar TL shortening was obtained following cells’ exposure to 25 µM acetaldehyde (AcH) and to a much lower extent after exposure to 4-methylpyrazolean, an inhibitor of alcoholdehydrogenase, suggesting that AcH plays a key role in ethanol-dependent telomere shortening. Telomerase activity was not involved in this effect. TRF2 and several TRF2 binding proteins increased their binding to TLs after ethanol treatment, implying their involvement in this effect. The methylation status of several sub-telomeric regions increased in response to EtOH exposure. Gene expression profiling showed distinct patterns in cells treated with EtOH and in cells recovered from EtOH. In addition to cellular ageing, the described telomere shortening may contribute to the carcinogenic potential of acute alcohol consumption; both are associated with the shortening of TLs and provide new insights regarding the moderate consumption of alcohol referred to as “social drinking.”

scholarly journals Childhood Maltreatment and Telomere Shortening: Preliminary Support for an Effect of Early Stress on Cellular Aging

2010 ◽  
Vol 67 (6) ◽  
pp. 531-534 ◽  
Author(s):  
Audrey R. Tyrka ◽  
Lawrence H. Price ◽  
Hung-Teh Kao ◽  
Barbara Porton ◽  
Sarah A. Marsella ◽  
...  
Keyword(s):  
Childhood Maltreatment ◽  
Cellular Aging ◽  
Telomere Shortening ◽  
Early Stress ◽  
Preliminary Support

scholarly journals Regulation of Gene Expression by Telomere Position Effect

2021 ◽  
Vol 22 (23) ◽  
pp. 12807
Author(s):  
Kyung-Ha Lee ◽  
Do-Yeon Kim ◽  
Wanil Kim
Keyword(s):  
Gene Expression ◽  
Structural Changes ◽  
Genome Rearrangement ◽  
Malignant Tumors ◽  
Human Life ◽  
Position Effect ◽  
Regulation Of Gene Expression ◽  
The Elderly ◽  
Cellular Aging ◽  
Telomere Shortening

Many diseases that involve malignant tumors in the elderly affect the quality of human life; therefore, the relationship between aging and pathogenesis in geriatric diseases must be under-stood to develop appropriate treatments for these diseases. Recent reports have shown that epigenetic regulation caused by changes in the local chromatin structure plays an essential role in aging. This review provides an overview of the roles of telomere shortening on genomic structural changes during an age-dependent shift in gene expression. Telomere shortening is one of the most prominent events that is involved in cellular aging and it affects global gene expression through genome rearrangement. This review provides novel insights into the roles of telomere shortening in disease-affected cells during pathogenesis and suggests novel therapeutic approaches.

scholarly journals FOXO3, Telomere Dynamics, and Healthy Brain Aging: A COBRE Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 368-368
Author(s):  
Bradley Willcox ◽  
Kamal Masaki ◽  
Richard Allsopp ◽  
Kalpana Kallianpur
Keyword(s):  
Brain Aging ◽  
Peripheral Blood Leukocyte ◽  
Telomerase Activity ◽  
Cellular Aging ◽  
Human Longevity ◽  
Telomere Shortening ◽  
Wide Range ◽  
Brain Structure And Function ◽  
Blood Leukocyte ◽  
And Function

Abstract Human longevity is linked to genetic, cellular, and other complex biological and psychosocial traits. Aging is typically accompanied by gradual brain atrophy and cognitive decline, but the mechanisms are unclear. Cellular aging, characterized by telomere shortening and altered telomerase activity, is related to mortality and brain aging. Decelerated brain aging is associated with greater peripheral blood leukocyte telomere length (LTL) and, we hypothesize, may be linked to FOXO3 genotype. We will use MRI to assess brain structure and function cross-sectionally in 100 Kuakini Honolulu Heart Program Offspring. Atrophy and disrupted functional connectivity, markers of brain aging, will be examined in relation to FOXO3 and LTL. Associations between brain structural and functional differences, FOXO3 genotype and LTL will be investigated over a wide range of ages, controlling for other biological and psychosocial factors. Results may provide insight into mechanisms influencing the rate of brain aging, and may eventually extend human healthspan.

scholarly journals Role of Telomeres Shortening in Atherogenesis: An Overview

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 395
Author(s):  
Yegor E. Yegorov ◽  
Anastasia V. Poznyak ◽  
Nikita G. Nikiforov ◽  
Antonina V. Starodubova ◽  
Alexander N. Orekhov
Keyword(s):  
Blood Cells ◽  
Causes Of Death ◽  
Measurement Data ◽  
Cellular Aging ◽  
Modern World ◽  
Atherosclerotic Plaques ◽  
Age Dependence ◽  
Telomere Shortening ◽  
Inflammatory Phenotype

It is known that the shortening of the telomeres leads to cell senescence, accompanied by acquiring of pro-inflammatory phenotype. The expression of telomerase can elongate telomeres and resist the onset of senescence. The initiation of atherosclerosis is believed to be associated with local senescence of the endothelial cells of the arteries in places with either low or multidirectional oscillatory wall shear stress. The process of regeneration of the artery surface that has begun does not lead to success for several reasons. Atherosclerotic plaques are formed, which, when developed, lead to fatal consequences, which are the leading causes of death in the modern world. The pronounced age dependence of the manifestations of atherosclerosis pushes scientists to try to link the development of atherosclerosis with telomere length. The study of the role of telomere shortening in atherosclerosis is mainly limited to measuring the telomeres of blood cells, and only in rare cases (surgery or post-mortem examination) are the telomeres of local cells available for measurement. The review discusses the basic issues of cellular aging and the interpretation of telomere measurement data in atherosclerosis, as well as the prospects for the prevention and possible treatment of atherosclerosis.

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