Cumulative Inflammatory Load Is Associated with Short Leukocyte Telomere Length in the Health, Aging and Body Composition Study

Abstract

BackgroundLeukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction.Methodology/Principal FindingsTo address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70–79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-α had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-α had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37–0.72), only IL-6 high (OR = 0.57, CI = 0.39–0.83) or only TNF-α high (OR = 0.67, CI = 0.46–0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL.Conclusions/SignificanceResults suggest that cumulative inflammatory load, as indexed by the combination of high levels of IL-6 and TNF-α, is associated with increased odds for short LTL. In contrast, high levels of CRP were not accompanied by short LTL in this cohort of older adults. These data provide the first large-scale demonstration of links between inflammatory markers and LTL in an older population.

Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population

“…The mechanism underlying a biological association between dietary factors (vegetables, meat, dairy, and cereal) and LTL is not evident. It is possible that inflammatory and oxidative pathways (de Vos-Houben et al 2012;O'Donovan et al 2011;von Zglinicki 2002) could be involved. Vegetables are the main dietary sources of flavonoids which are shown to have antioxidative activity (Yao et al 2004).…”

“…Although LTL is strongly influenced by genetic factors, telomere attrition might be modulated by environmental and lifestyle factors, including older age, cigarette smoking, gender, ethnicity (Diez Roux et al 2009), education ) and other indicators of socioeconomic status (Carroll et al 2013), and diet (Kiecolt-Glaser et al 2013). Inflammation (O'Donovan et al 2011) and oxidative stress (de Vos-Houben et al 2012;von Zglinicki 2002) may contribute to LTL shortening and may represent pathways for the LTL changes associated with various environmental or lifestyle factors (Kiecolt-Glaser et al 2013;Wolkowitz et al 2011).…”

Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study

“…Serum albumin was measured using the bromocresol green method. Blood concentrations of TNF-a, IL-6, and C-reactive protein (CRP) were measured in duplicate as described (11). Urine albumin and creatinine, serum albumin, TNF-a, CRP, and IL-6 measurements were not measured at year 3; however, they were measured at baseline.…”

Cell-free DNA and telomere length among women undergoing in vitro fertilization treatment

“…Telomere length is affected by recombination, epigenetic regulation, and genetic factors, as well as oxidative stress. Telomere length in peripheral leukocytes has been found to influence the risk of unexplained recurrent pregnancy loss [3] and cumulative inflammatory load [19]. There are no currently standardized telomere lengths that are considered norms for health; however, there are scientists currently working on developing a gold standard norm [20].…”

“…Chronically stressed caregivers anticipate greater threat to a standardized stressor compared to controls, and this anticipatory threat is associated with shorter telomeres [23]. Shortened telomere length has been associated with depression and cumulative inflammatory load [19,20,24].…”