For the first time, researchers from Newcastle University’s Institute for Ageing and Keio University School of Medicine in Tokyo examined which biological and pathological processes most strongly predict successful ageing beyond 100 years of age.
The team found that two factors stand out for reaching extreme old age: controlling chronic inflammation and maintaining relatively long telomeres—the protective caps at the ends of chromosomes that influence cellular ageing.
Chronic inflammation contributes to many age-related diseases, including diabetes and degenerative conditions affecting bones and joints, and it can itself become a persistent, damaging state that accelerates decline. The study shows that limiting this inflammatory burden is a key component of living longer and healthier lives.
Professor Thomas von Zglinicki of Newcastle University’s Institute for Ageing led the UK team. He explained: “Centenarians and semi-supercentenarians differ from the general population because they appear to age more slowly. They can resist disease for far longer than typical older adults.”
The researchers assessed multiple health markers across groups that included semi-supercentenarians (aged 105 and over), centenarians (100–104), people approaching 100 and the offspring of centenarians. Measured biomarkers covered blood cell counts, metabolism, liver and kidney function, markers of inflammation, and telomere length—factors the team considered likely contributors to successful ageing and longevity.
Although scientists generally expect telomeres to shorten with age, the study revealed that children of centenarians—who have a higher chance of becoming centenarians themselves—preserved telomere length at levels typical of people around 60 years old, even when these offspring reached 80 and beyond.
Professor von Zglinicki added: “Once people reach very advanced ages, telomere length no longer predicts further successful ageing. Still, our data show that centenarians and their offspring maintain longer telomeres than the general population. This suggests that preserved telomere length may be a necessary, or at least a helpful, factor in achieving extreme old age.”
Lower levels of inflammation predict better outcomes
The offspring of centenarians tended to have lower markers of chronic inflammation. While inflammatory markers rose with age across all groups, those who kept inflammation lower showed the best outcomes: better cognitive function, greater independence, and longer survival.
Professor von Zglinicki noted: “Chronic inflammation has long been linked to ageing in typical populations. Recent mechanistic work in animals shows inflammation can directly accelerate ageing. Our study is the first to demonstrate that inflammation levels predict successful ageing even among the extremely old, which strengthens the case that chronic inflammation drives human ageing as well.”
The findings indicate that inflammation is a modifiable driver of ageing that could be targeted by new therapies. “Designing novel, safe anti-inflammatory or immune-modulating treatments has major potential to improve healthy lifespan,” he said, while also cautioning that many currently available potent anti-inflammatory drugs have side effects that make them unsuitable for long-term use in older adults.
The study combined three large community-based Japanese cohorts: the Tokyo Oldest Old Survey on Total Health (TOOTH), the Tokyo Centenarians Study (TCS) and the Japanese Semi-Supercentenarians Study (JSS). In total, researchers analysed 1,554 individuals: 684 centenarians and semi-supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 very old community-dwelling participants. The age range covered participants from roughly 50 years up to the world’s oldest study participant at 115 years.
The primary objective was to identify biological markers that predict successful ageing in extreme old age and to determine whether centenarian offspring already show the beneficial biological profile associated with exceptional longevity. Understanding these determinants could help extend healthy lifespan more broadly and narrow the gap between the fastest- and slowest-ageing groups in the population.
Dr Yasumichi Arai, head of the TOOTH cohort and first author, said: “Our results suggest that suppressing chronic inflammation may help people age more slowly. However, many effective anti-inflammatory drugs are not appropriate for long-term use because of side effects, so developing safer alternatives could substantially improve the quality of life for older adults.”
Professor Nobuyoshi Hirose, head of the Tokyo Centenarians Study and the Japanese Semi-Supercentenarians Study, added: “If we can understand what distinguishes centenarians and supercentenarians, it may be possible to improve ageing outcomes for everyone.”
About the study and findings
The analysis used combined z scores from multiple biomarkers to represent domains such as haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence. In Cox proportional hazards models, the inflammation score predicted all-cause mortality in both the very old and semi-supercentenarian groups. In forward stepwise models, inflammation explained a meaningful portion of the variance in physical capability and cognitive function among the extremely old—more than chronological age or gender did in this cohort. Although centenarians and their offspring maintained relatively long telomeres, telomere length did not predict successful ageing among centenarians and semi-supercentenarians in these analyses. The authors conclude that inflammation is an important and potentially modifiable driver of human ageing up to the most extreme ages.
Source: Newcastle University
Image Credit: The image is in the public domain
Original Research: Full open access research for “Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians” by Yasumichi Arai M.D, Carmen M Martin-Ruiz PhD, Michiyo Takayama M.D, Yukiko Abe B.A, Toru Takebayashi M.D, Shigeo Koyasu PhD, Makoto Suematsu M.D, Nobuyoshi Hirose M.D, Thomas von Zglinicki PhD. in EBioMedicine. Published online August 4 2015 doi:10.1016/j.ebiom.2015.07.029
Abstract
Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians
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.