TY  - JOUR
AB  - Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from eight prospective population-based cohort studies, representing 13,021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had an excess mortality from all causes of 57 deaths per 10,000 person-years (95% confidence interval (CI): 38, 76) compared to their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10,000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the WHO risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.
AU  - Fiorito, G.*
AU  - Pedron, S.
AU  - Ochoa-Rosales, C.*
AU  - McCrory, C.*
AU  - Polidoro, S.*
AU  - Zhang, Y.*
AU  - Dugué, P.A.*
AU  - Ratliff, S.*
AU  - Zhao, W.N.*
AU  - Mckay, G.J.*
AU  - Costa, G.*
AU  - Solinas, M.G.*
AU  - Mullan Harris, K.*
AU  - Tumino, R.*
AU  - Grioni, S.*
AU  - Ricceri, F.*
AU  - Panico, S.*
AU  - Brenner, H.*
AU  - Schwettmann, L.
AU  - Waldenberger, M.
AU  - Matias-Garcia, P.R.
AU  - Peters, A.
AU  - Hodge, A.*
AU  - Giles, G.G.*
AU  - Schmitz, L.L.*
AU  - Levine, M.*
AU  - Smith, J.A.*
AU  - Liu, Y.*
AU  - Kee, F.*
AU  - Young, I.S.*
AU  - McGuinness, B.*
AU  - McKnight, A.J.*
AU  - van Meurs, J.*
AU  - Voortman, T.*
AU  - Kenny, R.A.*
AU  - Vineis, P.*
AU  - Carmeli, C.*
C1  - 64359
C2  - 52207
SP  - 1750-1759
TI  - The role of epigenetic clocks in explaining educational inequalities in mortality: A multi-cohort study and meta-analysis.
JO  - J. Gerontol. A Biol. Sci. Med. Sci.
VL  - 77
IS  - 9
PY  - 2022
SN  - 1079-5006
ER  - 

TY  - JOUR
AB  - Despite enormous research efforts, the genetic component of longevity has remained largely elusive. The investigation of common variants, mainly located in intronic or regulatory regions, has yielded only little new information on the heritability of the phenotype. Here, we performed a chip-based exome-wide association study investigating 62,488 common and rare coding variants in 1,248 German long-lived individuals, including 599 centenarians and 6,941 younger controls (age < 60 years). In a single-variant analysis, we observed an exome-wide significant association between rs1046896 in the gene fructosamine-3-kinase-related-protein (FN3KRP) and longevity. Noteworthy, we found the longevity allele C of rs1046896 to be associated with an increased FN3KRP expression in whole blood; a database look-up confirmed this effect for various other human tissues. A gene-based analysis, in which potential cumulative effects of common and rare variants were considered, yielded the gene phosphoglycolate phosphatase (PGP) as another potential longevity gene, though no single variant in PGP reached the discovery P-value (1x10E-04). Furthermore, we validated the previously reported longevity locus cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1). Replication of our results in a French longevity cohort was only successful for rs1063192 in CDKN2B-AS1. In conclusion, we identified two new potential candidate longevity genes, FN3KRP and PGP which may influence the phenotype through their role in metabolic processes, i.e. the reverse glycation of proteins (FN3KRP) and the control of glycerol-3-phosphate levels (PGP).
AU  - Torres, G.G.*
AU  - Nygaard, M.*
AU  - Caliebe, A.*
AU  - Blanché, H.*
AU  - Chantalat, S.*
AU  - Galan, P.*
AU  - Lieb, W.*
AU  - Christiansen, L.*
AU  - Deleuze, J.F.*
AU  - Christensen, K.*
AU  - Strauch, K.
AU  - Müller-Nurasyid, M.
AU  - Peters, A.
AU  - Nöthen, M.M.*
AU  - Hoffmann, P.*
AU  - Flachsbart, F.*
AU  - Schreiber, S.*
AU  - Ellinghaus, D.*
AU  - Franke, A.*
AU  - Dose, J.*
AU  - Nebel, A.*
C1  - 61213
C2  - 50100
CY  - Journals Dept, 2001 Evans Rd, Cary, Nc 27513 Usa
SP  - 786–795
TI  - Exome-wide association study identifies FN3KRP and PGP as new candidate longevity genes.
JO  - J. Gerontol. A Biol. Sci. Med. Sci.
VL  - 76
IS  - 5
PB  - Oxford Univ Press Inc
PY  - 2021
SN  - 1079-5006
ER  - 

TY  - JOUR
AB  - Death from chronic lung disease is increasing and Chronic Obstructive Pulmonary Disease has become the third leading cause of death in the United States in the past decade. Both chronic and acute lung diseases disproportionately affect elderly individuals, making it likely that these diseases will become more frequent and severe as the worldwide population ages. Chronic lung diseases are associated with substantial morbidity, frequently resulting in exercise limiting dyspnea, immobilization and isolation. Therefore, effective strategies to prevent or treat lung disease are likely to increase healthspan as well as lifespan. This review summarizes the findings of a joint workshop sponsored by the NIA and NHLBI that brought together investigators focused on aging and lung biology. These investigators encouraged the use of genetic systems and aged animals in the study of lung disease and the development of integrative systems-based platforms that can dynamically incorporate datasets that describe the genomics, transcriptomics, epigenomics, metabolomics and proteomics of the aging lung in health and disease. Further research was recommended to integrate benchmark biological hallmarks of aging in the lung with the pathobiology of acute and chronic lung diseases with divergent pathologies for which advanced age is the most important risk factor.
AU  - Budinger, G.S.*
AU  - Kohanski, R.A.*
AU  - Gan, W.*
AU  - Kobor, M.S.*
AU  - Amaral, L.A.*
AU  - Armanios, M.*
AU  - Kelsey, K.T.*
AU  - Pardo, A.*
AU  - Tuder, R.M.*
AU  - Macián, F.*
AU  - Chandel, N.S.*
AU  - Vaughan, D.*
AU  - Rojas, M.*
AU  - Mora, A.L.*
AU  - Kovacs, E.*
AU  - Duncan, S.R.*
AU  - Finkel, T.*
AU  - Choi, A.*
AU  - Eickelberg, O.
AU  - Chen, D.*
AU  - Agusti, A.*
AU  - Selman, M.*
AU  - Balch, W.E.*
AU  - Busse, P.J.*
AU  - Lin, A.*
AU  - Morimoto, R.*
AU  - Sznajder, J.I.*
AU  - Thannickal, V.J.*
C1  - 51108
C2  - 43085
TI  - The intersection of aging biology and the pathobiology of lung diseases: A joint NHLBI/NIA Workshop.
JO  - J. Gerontol. A Biol. Sci. Med. Sci.
PY  - 2017
SN  - 1079-5006
ER  - 

TY  - JOUR
AB  - Although genetic factors are known to influence the human aging process, the proportion of life span and longevity variation explained by them is still controversial. We evaluated the genetic contribution to life span using historical data from three Alpine communities in South Tyrol, Italy. We estimated the heritability of life span and survival to old age (longevity), and we assessed the hypothesis of a common genetic background between life span and reproduction. The heritability of life span was 0.15 (SE = 0.02), whereas the heritability of longevity increased from 0.20 to 0.35 as the longevity threshold increased. Heritability estimates were little influenced by shared environment, most likely due to the homogeneity of lifestyle and environmental factors in our study population. Life span showed both positive association and genetic correlation with reproductive history factors. Our study demonstrates a general low inheritance of human life span, but which increases substantially when considering long-living individuals, and a common genetic background of life span and reproduction, in agreement with evolutionary theories of aging.
AU  - Gögele, M.*
AU  - Pattaro, C.*
AU  - Fuchsberger, C.*
AU  - Minelli, C.*
AU  - Pramstaller, P.P.
AU  - Wjst, M.*
C1  - 5469
C2  - 27801
SP  - 26-37
TI  - Heritability analysis of life span in a semi-isolated population followed across four centuries reveals the presence of pleiotropy between life Span and reproduction.
JO  - J. Gerontol. A Biol. Sci. Med. Sci.
VL  - 66
IS  - 1
PB  - Oxford Univ. Press
PY  - 2011
SN  - 1079-5006
ER  -