title: Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians.
abstract: 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.
authors.affiliation: Centre for Supercentenarian Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle University, UK.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Martin-Ruiz
authors.affiliation: Centre for Preventive Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Takayama
authors.affiliation: Centre for Supercentenarian Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takebayashi
authors.affiliation: Laboratory 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.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
authors.affiliation: Centre 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.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Centre for Supercentenarian Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hirose
authors.affiliation: Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle University, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: von Zglinicki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers; D002423:Cause of Death; D016922:Cellular Senescence / Q000235:genetics; D005260:Female; D006801:Humans; D000068884:Immunosenescence / Q000235:genetics; D007249:Inflammation / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D053208:Kaplan-Meier Estimate; D008136:Longevity / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D009017:Morbidity; D016615:Telomere / Q000235:genetics*
chemical_list: D015415:Biomarkers
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