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

EBioMedicine. 2015 Jul 29;2(10):1549-58. doi: 10.1016/j.ebiom.2015.07.029. eCollection 2015 Oct.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Aging / metabolism
  • Biomarkers
  • Cause of Death
  • Cellular Senescence / genetics
  • Female
  • Humans
  • Immunosenescence / genetics
  • Inflammation / epidemiology
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Inflammation / mortality*
  • Kaplan-Meier Estimate
  • Longevity / genetics
  • Longitudinal Studies
  • Male
  • Morbidity
  • Telomere / genetics*


  • Biomarkers