TY - JOUR
T1 - Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age
T2 - A Longitudinal Study of Semi-supercentenarians
AU - Arai, Yasumichi
AU - Martin-Ruiz, Carmen M.
AU - Takayama, Michiyo
AU - Abe, Yukiko
AU - Takebayashi, Toru
AU - Koyasu, Shigeo
AU - Suematsu, Makoto
AU - Hirose, Nobuyoshi
AU - von Zglinicki, Thomas
N1 - Funding Information:
The study was supported by a grant from the Ministry of Health, Welfare, and Labour for the Scientific Research Project for Longevity (NH); the Grant-in-Aid for Scientific Research (C) (Nos. 20590706 (MT), 21590775 (YA), 24590898 (YA)) from the Japan Society for the Promotion of Science; the medical-welfare-food-agriculture collaborating consortium project from the Japan Ministry of Agriculture, Forestry, and Fisheries (TT); the Daiwa Anglo-Japanese Foundation (YA); grant G0601333 from the UK Medical Research Council and the Biotechnology and Biological Sciences Research Council (TvZ); a grant from Suntory Global Innovation Centre FY2014 (MS); the NIHR Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University (CMR); and the Biobank Japan Program from the Ministry of Education, Culture, Sports, and Technology (NH and MS). YAbe was supported by the medical-welfare-food-agriculture collaborating consortium project from the Japan Ministry of Agriculture, Forestry, and Fisheries.
Funding Information:
The sponsors had no role in the conduct or interpretation of the study. YA received research grants from DAIICHI SANKYO Co, Ltd and Takeda Pharmaceutical Company Ltd. NH received a research grant from MSD K.K. SK is a consultant for Medical and Biological Laboratories, Co. Ltd. The authors had no financial relationships with any other organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.
Publisher Copyright:
© 2015.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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 99years). 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.
AB - 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 99years). 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.
KW - Ageing
KW - Centenarian
KW - Inflammation
KW - Telomere
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U2 - 10.1016/j.ebiom.2015.07.029
DO - 10.1016/j.ebiom.2015.07.029
M3 - Article
C2 - 26629551
AN - SCOPUS:84949724978
SN - 2352-3964
VL - 2
SP - 1549
EP - 1558
JO - EBioMedicine
JF - EBioMedicine
IS - 10
ER -