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

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

Yasumichi Arai  1 , Carmen M Martin-Ruiz  2 , Michiyo Takayama  3 , Yukiko Abe  1 , Toru Takebayashi  4 , Shigeo Koyasu  5 , Makoto Suematsu  6 , Nobuyoshi Hirose  1 , Thomas von Zglinicki  2
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Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians

Yasumichi Arai et al. EBioMedicine. .
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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.

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.

Figures

Fig. 1
Telomere length in study participants up to 115 years of age. Leukocyte telomere length vs age is shown for males (blue or cyan) and females (green or red). Centenarians, (semi-)supercentenarians, and centenarian offspring are shown in blue (males) or red (females), respectively. Unrelated participants younger than 100 years are indicated in cyan (males) or green (females). Regression lines belonging to these groups are indicated by the same colour.
Fig. 2
Kaplan–Meier survival curves for tertiles of biomarker domains and telomere length in the very old, centenarian, and (semi-)supercentenarian group. For each age group, the domains were independently organized into tertiles and assessed as independent predictors of survival. The p-value indicates the significance of the log-rank Mantel–Cox test of equality of survival distributions.
Fig. 3
Predictors of capability (a), cognition (b), and multi-morbidity (c). Forward stepwise model selection was performed with age, gender, and all domain scores as predictors. Models were run separately for all unrelated participants and for each of the indicated age groups. Bars indicate the percentage of target variance explained by each predictor. All significant predictors (p 
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