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Cellular Aging

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Submitted By slik419
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Jovanny Quesada
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Epel ES, Blackburn EH, Lin J et. al. (2004). Accelerated telomere shortening in response to life stress. PNAS. 101, 49, 17312-17315.
Chronic stress has been demonstrated to be correlated with poor health in various studies which include risks to cardiovascular disease and poor immune function (Epel et. al, 2004). Epel et. al investigates whether stress may accelerate cellular aging translating to diseases associated with organismal aging. Telomeres, a vital component of chromosomes, provides chromosomal stability as a repeated nucleotide sequence cap. DNA Polymerase struggles to replicate the ends of linear molecules therefore the ends of telomeres are not fully replicated causing telomeres to shorten with each replication in somatic cells (Epel et. al). As a result, their length are typically used as a measure of biological “age”. Additionally, telomerase is another crucial component considered to analyze cellular aging. Telomerase is an enzyme that catalyzes the addition of required T2AG3 repeats onto 3’ ends of the telomeres; individuals with diminished telomerase may suffer from shortened telomeres (Epel et. al).
Zglinicki et. al has demonstrated in vitro that oxidative stress can result in shortened telomeres and notably perceived stress has been linked to oxidative stress in leukocytes. Epel et. al hypothesize that chronic psychological stress may result in telomere shortening, oxidative stress, and reduced telomerase activity in peripheral blood mononuclear cells (PBMC). Objective and subjective stress is studied to examine its importance in cellular aging. To differentiate subjective and objective stress 58 healthy premenopausal mothers of either a healthy (control mothers) or chronically ill child (caregiving mothers) were studied. There are many factors that may alter any conclusive results such as age, BMI, smoking, use of multivitamins or antioxidants. With all these factors controlled stress was significantly associated with shorter telomeres and reduced telomerase activity (Epel et. al).
Cell senescence is influenced by chronic or perceived life stress by the following non-mutually exclusive pathways: immune cell function, oxidative stress, or telomerase activity (Epel et. al). To determine if the immune cell function pathway is responsible, Epel et. al investigated the proportion of naïve T cells and memory T cells. Memory T cells have shorter telomere length than naïve T cells however the data does not support this conclusion (Epel et. al). In contrast, self-reported stress in woman is related to increased oxidative DNA damage; Zglinicki et. al also reports that oxidative stress shortens telomeres in vitro as stated prior therefore it is likely that caregiving mothers are susceptible to oxidative stress and shortened telomeres. Although being a caregiving mother is not related to telomere length, chronicity of caregiving stress was related to telomere length however it is a possibility that this association is due to psychological resistance to objective stressors in individuals with long telomere length (Epel et. al). A vital future study should examine the rate of telomere shortening with lowered perceived stress in adults. Lastly, Epel et. al observed lowered telomerase activity which may contribute to the shortened telomeres in PBMC.
A concomitant study by Chen et. al investigates relationship of adverse childhood experiences (ACE) to leukocyte telomere length (LTL) in individuals with major depressive disorder (MDD). (Lot of initials right?). ACEs is associated with poor physical and mental health; this denotes the high incidence of ACE in individuals with MDD (Chen et. al, 2014). Surprisingly, no other study has considered MDD in the study despite the high incidence of it in ACE. The results demonstrate there is shortened LTL in healthy adults with a history of multiple ACE.
Vocabulary:
Putative - generally considered or reputed to be. (I think this is my second time I had to look it up )
Flow cytometry - a laser-based, biophysical technology employed in cell counting, cell sorting, biomarker detection and protein engineering, by suspending cells in a stream of fluid and passing them by an electronic detection apparatus.
References:
* Zglinicki, T. (n.d.). Oxidative stress shortens telomeres. Trends in Biochemical Sciences, 339-344. * Chen, S., Epel, E., Mellon, S., Lin, J., Reus, V., Rosser, R. Wolkowitz, O. (n.d.). Adverse childhood experiences and leukocyte telomere maintenance in depressed and healthy adults. Journal of Affective Disorders, 86-90.

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