Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection

Abstract

Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.

Social stress shortens lifespan in mice

“…In landmark studies, Epel and colleagues (Blackburn, Epel & Lin, 2015; Epel et al., 2004) identified the association between exposure to life stress, shortening of leukocyte telomeres, and mortality in humans. The discrepancy with our current results could be attributed to intrinsic factors such as tissue specificity, species, and gender in the measure of telomere length (Sanders & Newman, 2013).…”

Cellular aging dynamics after acute malaria infection: A 12‐month longitudinal study

“…Telomeres, the end parts of chromosomes that consist of tandem repeats of noncoding DNA, shorten as part of normal aging (Blackburn, Epel, & Lin, 2015) and also due to various types of intrinsic and extrinsic factors (Blackburn & Epel, 2012; Epel et al., 2004). Shorter telomere length has been linked to human pathologies such as cardiovascular disease, stroke, diabetes, dementia, and immune dysfunction (Atzmon et al., 2010).…”

“…Shorter telomere length has been linked to human pathologies such as cardiovascular disease, stroke, diabetes, dementia, and immune dysfunction (Atzmon et al., 2010). Large cohort studies have shown that shorter telomere length is a significant predictor of all‐cause mortality even after controlling for age and other known risk factors (Blackburn et al., 2015; Needham et al., 2015; Rode, Nordestgaard, & Bojesen, 2015). To counteract the progressive telomere shortening, stem cells and progenitor cells as well as a majority of cancer cells express telomerase (an enzyme capable of adding the telomeric repeats); however, in somatic cells, telomerase is downregulated to avoid tumor formation (Artandi & DePinho, 2010).…”

Telomere in Aging and Age-Related Diseases

“…(129) not only the apparent signs such as gray hair, wrinkle and spotting skin, muscle wasting, altered adiposity, but aging increase the susceptibility to diseases as people enter the last decades of life, including sufficient immune function, cardiovascular diseases (CVD), cancers, type 2 diabetes mellitus (T2DM), depression, and especially cognitive decline, although they are also could happened as comorbid disease in younger people. (20) Both aging and disease result in the same outcome: the impairment of normal biological function. It would not, therefore, be a surprise if tissue dysfunction resulting from an aging mechanism eventually manifested itself as a disease.…”

“…(20) Telomere roles as a cap to protect the genomic DNA through various mechanisms. One of it is by preventing the recognition of the linear chromosomal DNA end as a broken end, because once it was recognize as a broken end, automatically DNA end-joining, DNA recombination, or DNA repair mechanisms will be processed, leading to unstable chromosomes.…”