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Exposure to benzene, a known leukemogen and probable lymphomagen, has been demonstrated to result in oxidative stress, which has previously been associated with altered telomere length (TL). TL specifically has been associated with several health outcomes in epidemiologic studies, including cancer risk, and has been demonstrated to be altered following exposure to a variety of chemical agents. To evaluate the association between benzene exposure and TL, we measured TL by monochrome multiplex quantitative PCR in 43 workers exposed to high levels of benzene and 43 age and sex-matched unexposed workers in Shanghai, China. Benzene exposure levels were monitored using organic vapor passive dosimetry badges before phlebotomy. The median benzene exposure level in exposed workers was 31 ppm. The mean TL in controls, workers exposed to levels of benzene below the median (≤31 ppm), and above the median (>31 ppm) was 1.26 ± 0.17, 1.25 ± 0.16, and 1.37 ± 0.23, respectively. Mean TL was significantly elevated in workers exposed to >31 ppm of benzene compared with controls (P = 0.03). Our findings provide evidence that high levels of occupational benzene exposure are associated with TL. Environ.

BACKGROUND Leukocyte 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 FINDINGS To 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.BACKGROUND Leukocyte 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 FINDINGS To 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 Results 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.

BackgroundTelomeres shorten as cells divide. This shortening is compensated by the enzyme telomerase. We evaluated the effect of common variants in the telomerase RNA component (TERC) gene on telomere length (TL) in the population-based Health Aging and Body Composition (Health ABC) Study and in two replication samples (the TwinsUK Study and the Amish Family Osteoporosis Study, AFOS).MethodologyFive variants were identified in the TERC region by sequence analysis and only one SNP was common (rs2293607, G/A). The frequency of the G allele was 0.26 and 0.07 in white and black, respectively. Testing for association between TL and rs2293607 was performed using linear regression models or variance component analysis conditioning on relatedness among subjects.ResultsThe adjusted mean TL was significantly shorter in 665 white carriers of the G allele compared to 887 non-carriers from the Health ABC Study (4.69±0.05 kbp vs. 4.86±0.04 kbp, measured by quantitative PCR, p = 0.005). This association was replicated in another white sample from the TwinsUK Study (6.90±0.03 kbp in 301 carriers compared to 7.06±0.03 kbp in 395 non-carriers, measured by Southern blots, p = 0.009). A similar pattern of association was observed in whites from the family-based AFOS and blacks from the Health ABC cohort, although not statistically significant, possibly due to the lower allele frequency in these populations. Combined analysis using 2,953 white subjects from 3 studies showed a significant association between TL and rs2293607 (β = -0.19±0.04 kbp, p = 0.001).ConclusionOur study shows a significant association between a common variant in TERC and TL in humans, suggesting that TERC may play a role in telomere homeostasis.

Although telomere length (TL) is known to play a critical role in cellular senescence, the relationship of TL to aging and longevity in humans is not well understood. In a large biracial population-based cohort, we tested the hypotheses that elderly persons with shorter TL in peripheral white blood cells have poorer survival, shorter life span, and fewer years of healthy life (YHL). Associations were evaluated using Cox proportional hazard models and linear regression analyses where appropriate. TL (in kilo base pairs) was not associated with overall survival (hazard ratio 1.0: 95% confidence interval 0.9-1.1) or death from any specific underlying cause including infectious diseases, cancer, or cardiac and cerebrovascular diseases. TL, however, was positively associated with more YHL ([beta] = 0.08 [+ or -] 0.04, p = .03). Findings suggest that TL may not be a strong biomarker of survival in older individuals, but it may be an informative biomarker of healthy aging. Key Words: Telomere--Survival--Life span--Health status--Years of healthy life.

Women giving birth at advanced reproductive ages in natural fertility conditions have been shown to have superior postmenopausal longevity. It is unknown whether improved survival is more likely among relatives of late-fertile women. This study compares survival past age 50 of men with and without a late-fertile sister in two populations: Utahns born in 1800-1869 identified from the Utah Population Database and Quebec residents born in 1670-1750 identified from the Programme de recherche en demographie historique. Male survival was greater for those with, rather than without, a sister reproducing after age 45, particularly among men with at least three sisters (Utah rate ratio [RR] = .801, 95% CI = 0.687-0.940; Quebec RR = .786, 95% CI = 0.664-0.931). Survival of wives was unaffected by whether their husbands had a late-fertile sister, suggesting a weak influence of unmeasured socioenvironmental factors. These results support the hypothesis that late female fertility and slow somatic aging may be promoted by the same genetic variants. Key Words: Survival--Longevity--Reproduction--Aging--Natural fertility.

Background: Critically shortened telomeres contribute to chromosomal instability and neoplastic transformation and are associated with early death of patients with certain cancer types. Shorter leukocyte telomere length (LTL) has been associated with higher risk for pancreatic ductal adenocarcinoma (PDAC) and might be associated also with survival of patients with PDAC. We investigated the association between treatment-naïve LTL and overall survival of patients with incident PDAC. Methods: The study included 642 consecutively enrolled PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreas Research. Blood samples were obtained at the time of diagnosis, before the start of cancer treatment, from which LTL was assayed by qRT-PCR. LTL was first modeled as a continuous variable (per-interquartile range decrease in LTL) and then as a categorized variable (short, medium, long). Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated for overall mortality using Cox proportional hazard models. Results: Shorter treatment-naïve LTL was associated with higher mortality among patients with PDAC (HRcontinuous = 1.13, 95% CI: 1.01-1.28, P = 0.03; HRshortest vs. longest LTL = 1.29, 95% CI: 1.05-1.59, Ptrend = 0.01). There was a difference in the association between LTL and overall mortality by tumor stage at diagnosis; resectable tumors (HRcontinuous = 0.91; 95% CI: 0.73-1.12), locally advanced tumors (HRcontinuous = 1.29; 95% CI: 1.07-1.56), and metastatic tumors (HRcontinuous = 1.17; 95% CI: 0.96-1.42), Pinteraction = 0.04. Conclusion: Shorter treatment-naïve LTL is associated with poorer overall survival of patients with incident PDAC. Impact: Peripheral blood LTL might be a prognostic marker for PDAC. [ABSTRACT FROM AUTHOR]

We evaluated the influence of family history on longevity by examining longevity in a cohort of 78,994 individuals drawn from the Utah Population Database (UPDB) who were born between 1870 and 1907, and lived to at least age 65. We examined Mendelian genetic and social modes of transmission of excess longevity (the difference between observed and expected longevity) by varying weighted kinship contributions over different classes of relatives. The genetic component of the variation in excess longevity measured as heritability, [h.sup.2], was approximately 0.15 (95% confidence interval [CI] 0.12-0.18). Among siblings of probands who reached the 97th percentile of excess longevity (+ 14.8 years, currently age 95 for men and 97 for women), the relative risk of recurrence ([[Lambda].sub.s]) was 2.30 (95% CI 2.08-2.56). In sibships whose relatives were in the top 15% of the distribution for familial excess longevity, the value of [[Lambda].sub.s] increased substantially, indicating that considering the longevity of distant relatives may be helpful in the selection of families in which to identify genes influencing aging and longevity.

Telomeres are repeating DNA at chromosome ends. Telomere length (TL) declines with age in most human tissues, and shorter TL is thought to accelerate senescence. In contrast, older men have sperm with longer TL; correspondingly, older paternal age at conception (PAC) predicts longer TL in offspring. This PAC-effect could be a unique form of transgenerational genetic plasticity that modifies somatic maintenance in response to cues of recent ancestral experience. The PAC-effect has not been examined in any non-human mammals. Objectives Here, we examine the PAC-effect in chimpanzees ( Pan troglodytes). The PAC-effect on TL is thought to be driven by continual production of sperm-the same process that drives increased de novo mutations with PAC. As chimpanzees have both greater sperm production and greater sperm mutation rates with PAC than humans, we predict that the PAC-effect on TL will be more pronounced in chimpanzees. Additionally we examine whether PAC predicts TL of grandchildren. Materials and methods TL were measured using qPCR from DNA from blood samples from 40 captive chimpanzees and 144 humans. Results Analyses showed increasing TL with PAC in chimpanzees ( p = .009) with a slope six times that in humans ( p = .026). No associations between TL and grandpaternal ages were found in humans or chimpanzees-although statistical power was low. Discussion These results suggest that sperm production rates across species may be a determinant of the PAC-effect on offspring TL. This raises the possibility that sperm production rates within species may influence the TL passed on to offspring. [ABSTRACT FROM AUTHOR]