Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians.

Author: Arai Y1, Martin-Ruiz CM2, Takayama M3, Abe Y1, Takebayashi T4, Koyasu S5, Suematsu M6, Hirose N1, von Zglinicki T2.
Affiliation: 1Centre for Supercentenarian Research, Keio University School of Medicine, Tokyo, Japan. 2Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle University, UK. 3Centre for Preventive Medicine, Keio University School of Medicine, Tokyo, Japan. 4Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan. 5Laboratory for Immune Cell Systems, RIKEN Centre for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan ; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. 6Centre for Supercentenarian Research, Keio University School of Medicine, Tokyo, Japan ; Department of Biochemistry, Keio University School of Medicine, and JST, ERATO, Suematsu Gas Biology Project, Tokyo, Japan.
Conference/Journal: EBioMedicine.
Date published: 2015 Jul 29
Other: Volume ID: 2 , Issue ID: 10 , Pages: 1549-58 , Special Notes: doi: 10.1016/j.ebiom.2015.07.029 , Word Count: 276



To determine the most important drivers of successful ageing at extreme old age, we combined community-based prospective cohorts: Tokyo Oldest Old Survey on Total Health (TOOTH), Tokyo Centenarians Study (TCS) and Japanese Semi-Supercentenarians Study (JSS) comprising 1554 individuals including 684 centenarians and (semi-)supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 community-living very old (85 to 99 years). We combined z scores from multiple biomarkers to describe haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence domains. In Cox proportional hazard models, inflammation predicted all-cause mortality with hazard ratios (95% CI) 1.89 (1.21 to 2.95) and 1.36 (1.05 to 1.78) in the very old and (semi-)supercentenarians, respectively. In linear forward stepwise models, inflammation predicted capability (10.8% variance explained) and cognition (8(.)6% variance explained) in (semi-)supercentenarians better than chronologic age or gender. The inflammation score was also lower in centenarian offspring compared to age-matched controls with Δ (95% CI) = - 0.795 (- 1.436 to - 0.154). Centenarians and their offspring were able to maintain long telomeres, but telomere length was not a predictor of successful ageing in centenarians and semi-supercentenarians. We conclude that inflammation is an important malleable driver of ageing up to extreme old age in humans.
KEYWORDS:
ALT, alanine aminotransferase or alanine transaminase; ANOVA, analysis of variance; AST, aspartate aminotransferase or aspartate transaminase; Ageing; CD, cluster of differentiation; CMV, cytomegalovirus; CRP, C-reactive protein; CVD, cardiovascular disease; Centenarian; ELISA, enzyme-linked immunosorbent assay; GGTP, gamma-glutamyl-transpeptidase; IL-6, interleukin 6; IQR, inter-quartile range; Inflammation; JSS, Japanese Semi-Supercentenarians Study; LTL, leukocyte telomere length; MMSE, Mini-Mental State Examination; NK cells, natural killer cells; PCR, polymerase chain reaction; SD, standard deviation; TCS, Tokyo Centenarians Study; TNF-alpha, tumour necrosis factor-alpha (TNF-alpha); TOOTH, Tokyo Oldest Old Survey on Total Health; Telomere; eGFR, estimated glomerular filtration rate
PMID: 26629551