Shorter Telomeres in Peripheral Blood Mononuclear Cells from Older Persons with Sarcopenia: Results from an Exploratory Study

Abstract

Background: Telomere shortening in peripheral blood mononuclear cells (PBMCs) has been associated with biological age and several chronic degenerative diseases. However, the relationship between telomere length and sarcopenia, a hallmark of the aging process, is unknown. The aim of the present study was therefore to determine whether PBMC telomeres obtained from sarcopenic older persons were shorter relative to non-sarcopenic peers. We further explored if PBMC telomere length was associated with frailty, a major clinical correlate of sarcopenia.Methods: Analyses were conducted in 142 persons aged ≥65 years referred to a geriatric outpatient clinic (University Hospital). The presence of sarcopenia was established according to the European Working Group on Sarcopenia in Older People criteria, with bioelectrical impedance analysis used for muscle mass estimation. The frailty status was determined by both the Fried’s criteria (physical frailty, PF) and a modified Rockwood’s frailty index (FI). Telomere length was measured in PBMCs by quantitative real-time polymerase chain reaction according to the telomere/single-copy gene ratio (T/S) method.Results: Among 142 outpatients (mean age 75.0 ± 6.5 years, 59.2% women), sarcopenia was diagnosed in 23 individuals (19.3%). The PF phenotype was detected in 74 participants (52.1%). The average FI score was 0.46 ± 0.17. PBMC telomeres were shorter in sarcopenic subjects (T/S = 0.21; 95% CI: 0.18–0.24) relative to non-sarcopenic individuals (T/S = 0.26; 95% CI: 0.24–0.28; p = 0.01), independent of age, gender, smoking habit, or comorbidity. No significant associations were determined between telomere length and either PF or the FI.Conclusion: PBMC telomere length, expressed as T/S values, is shorter in older outpatients with sarcopenia. The cross-sectional assessment of PBMC telomere length is not sufficient at capturing the complex, multidimensional syndrome of frailty.

No strong correlations between serum cytokine levels, CMV serostatus and hand-grip strength in older subjects in the Berlin BASE-II cohort

“…In the younger BASE-II cohort with participants maximally 85 years old, we found that telomere length values did correlate significantly with HGS. Results of another study revealed shorter telomeres in PBMCs of elderly people with sarcopenia compared to controls, whereby the authors point out that telomere shortening only provides one part of the understanding of frailty and more factors are involved (Marzetti et al 2014). Baylis et al reported that telomere attrition is linked to lower HGS in the longitudinal Hertfordshire Ageing Study.…”

Association of a biomarker-based frailty index with telomere length in older US adults: Findings from NHANES 1999-2002

“…However, a definitive association between these two correlates of aging has not been established - multiple studies investigating this link found no association. In this study, we reexamined this question using a novel laboratory measure-based index of frailty (FL) which focuses on sub-clinical/pre-clinical deficits, in contrast to previously commonly used frailty measures (FI and FP) which are largely based on clinically observable deficits, and which have not demonstrated significant associations with telomere length (Breitling et al, 2016; Collerton et al, 2012; Marzetti et al, 2014; Saum et al, 2014; Woo et al, 2008; Yu et al, 2015). In a covariate-adjusted model, we found a significant association between increased FL and decreased LTL.…”

“…diseases, disabilities, functional impairments), with higher scores indicating higher frequency and accumulation of age-related adverse health conditions (Xue, 2011). So far, studies examining the relationship of these clinical frailty measures with telomere length have found no association (Breitling et al, 2016; Collerton et al, 2012; Marzetti et al, 2014; Saum et al, 2014; Woo, Tang, Suen, Leung, & Leung, 2008; Yu, Tang, Leung, & Woo, 2015). This leaves open the question of how cellular senescence (of which telomere length is an indicator) eventually leads to clinical deficits seen among frail individuals.…”

Oxidative stress, genomic features and DNA repair in frail elderly: A systematic review

“…The observation that telomeres shorten over the life course has led to the hypothesis that telomere attrition may be a mechanism driving the ageing process (Mikhelson and Gamaley, 2012). Nevertheless, all the studies reviewed here failed in finding an association between frailty and TL shortening: Collerton et al (2012), using both Fried's criteria and FI (40 deficits; n = 552), Marzetti et al (2014) (n = 142) and Yu et al (2015Yu et al ( ) (n = 2006 employing the Fried's criteria, Saum et al (2014) (n = 3537) and Woo et al (2008Woo et al ( ) (n = 2006 using the FI (34 and 17 deficits, respectively). Lack of association between TL and frailty (Fried's criteria) was also obtained by Brault et al (2014) in older subjects with cardiovascular disease (n = 53); however, in this case, they found an unexpected association between longer leukocyte and aortic T/S ratio(mean telomere repeat copy to single gene copy number) and greater number of clinical frailty criteria.…”

“…Telomeres are regions of repetitive nucleotide sequence at each end of the chromosomes, which contribute to maintain their integrity. They progressively shorten as the cell divides, limiting the number of divisions that normal somatic cells can undergo (Marzetti et al, 2014). The observation that telomeres shorten over the life course has led to the hypothesis that telomere attrition may be a mechanism driving the ageing process (Mikhelson and Gamaley, 2012).…”