Is Telomere Length a Biomarker of Aging? A Review

Centre for Mental Health Research, Australian National University, Canberra, Australia.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences (Impact Factor: 5.42). 10/2010; 66(2):202-13. DOI: 10.1093/gerona/glq180
Source: PubMed


Telomeres, the DNA–protein structures located at the ends of chromosomes, have been proposed to act as a biomarker of aging.
In this review, the human evidence that telomere length is a biomarker of aging is evaluated. Although telomere length is
implicated in cellular aging, the evidence suggesting telomere length is a biomarker of aging in humans is equivocal. More
studies examining the relationships between telomere length and mortality and with measures that decline with “normal” aging
in community samples are required. These studies would benefit from longitudinal measures of both telomere length and aging-related

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    • "Thus, it has been hypothesized that folate deficiency or vitamin B 12 deficiency, accompanied by elevated levels of HCY, may disrupt genomic stability and the normal methylation state of genes[3,4]. Many epidemiological studies have examined the associa-tions of circulating folate, vitamin B 12 , and HCY levels with leukocyte telomere length (LTL)56789101112, which is considered a biomarker of cellular aging[13]. Several mechanisms have been suggested to underlie this association. For example, one proposal is that deficiencies of folate and vitamin B 12 influence genomic instability, which results in the attrition of telomere length. "
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    ABSTRACT: Folate, vitamin B12, and homocysteine (HCY) are involved in the metabolism of nucleic acid precursors and it has been hypothesized that they also influence telomere length, a biomarker of aging. However, previous studies have reported inconsistent findings, and data for older adults are limited. Our study aimed to evaluate associations between leukocyte telomere length (LTL) and serum folate, vitamin B12, and HCY levels among adults aged 55 years and over. In a cross-sectional study in 798 men and women aged 55-79 years, serum folate, vitamin B12, and HCY levels were measured using chemiluminescent immunometric assays, and relative LTL was assessed using quantitative real-time polymerase chain reaction. To evaluate associations between LTL and serum folate, vitamin B12, and HCY levels, multiple linear regression models were used. In multiple models adjusted for age, sex, serum high sensitive C-reactive protein (hs-CRP) levels, and other potential confounding factors, we found no association between LTL and serum folate, vitamin B12, and HCY levels. However, we did find a significant inverse association between HCY levels and LTL in participants with serum hs-CRP levels of ≥ 2 mg/L (p < 0.05). Moreover, there was a trend toward an association between HCY and vitamin B12 levels in these individuals (p = 0.08). In those with serum hs-CRP levels of < 2 mg/L, HCY was inversely associated with vitamin B12 levels (p < 0.001) and had no association with LTL. Our findings suggest that increased serum HCY levels, when combined with the presence of systemic inflammation, may play a role in accelerating biological aging.
    Full-text · Article · Jan 2016
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    • "The aging process is complex with significant changes in many different molecules, and some of these molecules can be used as aging indicators (Menni et al., 2013). Several aging markers have been identified , such as telomere length, reactive oxygen species levels, and caveolin-1 expression status (Cho et al., 2004; Mather et al., 2011; Pandey and Rizvi, 2010). "
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    ABSTRACT: Toll-like receptor 5 (TLR5) is a specific receptor for microbial flagellin and is one of the most well-known receptors in the TLR family. We reported previously that TLR5 signaling is well maintained during aging and that caveolin-1 may be involved in TLR5 signaling in aged macrophages through direct interactions. Therefore, it is important to clarify whether caveolin-1/TLR5 interactions affect TLR5 expression during aging. To assess the effect of caveolin-1 on TLR5, we analyzed TLR5 expression in senescent fibroblasts and aged tissues expressing high levels of caveolin-1. As expected, TLR5 mRNA and protein expression was well maintained in senescent fibroblasts and aged tissues, whereas TLR4 mRNA and protein were diminished in those cells and tissues. To determine the mechanism of caveolin-1-dependent TLR5 expression, we examined TLR5 expression in caveolin-1 deficient mice. Interestingly, TLR5 mRNA and protein levels were decreased dramatically in tissues from caveolin-1 knockout mice. Moreover, overexpressed caveolin-1 in vitro enhanced TLR5 mRNA through the MAPK pathway and prolonged TLR5 protein half-life through direct interaction. These results suggest that caveolin-1 may play a crucial role in maintaining of TLR5 by regulating transcription systems and increasing protein half-life.
    Preview · Article · Nov 2015 · Moleculer Cells
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    • "As many authors have acknowledged, understanding the factors driving among-and within-individual variation in LTL demands longitudinal collection of samples across the entire lifespan of the organism in question (e.g. Aviv, 2008; Mather et al., 2011; Benetos et al., 2013). Our own species' long and continually extending life expectancy means such data sets are currently unavailable, and it remains unclear to what degree telomere dynamics measured in "
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    ABSTRACT: Telomeres play a fundamental role in the maintenance of genomic integrity at a cellular level, and average leukocyte telomere length (LTL) has been proposed as a biomarker of organismal aging. However, studies tracking LTL across the entire life course of individuals are lacking. Here, we examined lifelong patterns of variation in LTL among four birth cohorts of female Soay sheep (Ovis aries) that were longitudinally monitored and sampled from birth to death. Over the first 4 months of life, there was within-individual loss of LTL, consistent with findings in the human and primate literature, but there was little evidence of consistent LTL loss associated with age after this point. Overall, we observed only weak evidence of individual consistency in LTL across years and over the entire lifespan: Within-individual variation was considerable, and birth cohorts differed markedly in their telomere dynamics. Despite the high levels of LTL variation within the lifetimes of individuals, there remained significant associations between LTL and longevity. Detailed analysis of the longitudinal data set showed that this association was driven by improved survival of individuals with longer LTL over the first 2 years of life. There was no evidence that LTL predicted survival in later adulthood. Our data provide the first evidence from a mammal that LTL can predict mortality and lifespan under natural conditions, and also highlight the potentially dynamic nature of LTL within the lifetimes of individuals experiencing a complex and highly variable environment.
    Full-text · Article · Nov 2015 · Aging cell
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