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Advancing front of old-age human survival.

ABSTRACT: Old-age mortality decline has driven recent increases in lifespans, but there is no agreement about trends in the age pattern of old-age deaths. Some argue that old-age deaths should become compressed at advanced ages, others argue that old-age deaths should become more dispersed with age, and yet others argue that old-age deaths are consistent with little change in dispersion. However, direct analysis of old-age deaths presents unusual challenges: Death rates at the oldest ages are always noisy, published life tables must assume an asymptotic age pattern of deaths, and the definition of "old-age" changes as lives lengthen. Here we use robust percentile-based methods to overcome some of these challenges and show, for five decades in 20 developed countries, that old-age survival follows an advancing front, like a traveling wave. The front lies between the 25th and 90th percentiles of old-age deaths, advancing with nearly constant long-term shape but annual fluctuations in speed. The existence of this front leads to several predictions that we verify, e.g., that advances in life expectancy at age 65 y are highly correlated with the advance of the 25th percentile, but not with distances between higher percentiles. Our unexpected result has implications for biological hypotheses about human aging and for future mortality change.

SUBMITTER: Zuo W

PROVIDER: S-EPMC6217443 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Advancing front of old-age human survival.

Zuo Wenyun W Jiang Sha S Guo Zhen Z Feldman Marcus W MW Tuljapurkar Shripad S

Proceedings of the National Academy of Sciences of the United States of America 20181016 44

Old-age mortality decline has driven recent increases in lifespans, but there is no agreement about trends in the age pattern of old-age deaths. Some argue that old-age deaths should become compressed at advanced ages, others argue that old-age deaths should become more dispersed with age, and yet others argue that old-age deaths are consistent with little change in dispersion. However, direct analysis of old-age deaths presents unusual challenges: Death rates at the oldest ages are always noisy ...[more]

PMID: 30327342

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Project description:BackgroundSurvival remains an issue in pulmonary hypertension, a chronic disorder that often affects aged human adults. In young adult mice and rats, chronic 50% hypoxia (11% FIO2 or 0.5 atm) induces pulmonary hypertension without threatening life. In this framework, oral dehydroepiandrosterone was recently shown to prevent and reverse pulmonary hypertension in rats within a few weeks. To evaluate dehydroepiandrosterone therapy more globally, in the long term and in old age, we investigated whether hypoxia decreases lifespan and whether dehydroepiandrosterone improves survival under hypoxia.Methods240 C57BL/6 mice were treated, from the age of 21 months until death, by normobaric hypoxia (11% FIO2) or normoxia, both with and without dehydroepiandrosterone sulfate (25 mg/kg in drinking water) (4 groups, N = 60). Survival, pulmonary artery and heart remodeling, weight and blood patterns were assessed.ResultsIn normoxia, control mice reached the median age of 27 months (median survival: 184 days). Hypoxia not only induced cardiopulmonary remodeling and polycythemia in old animals but also induced severe weight loss, trembling behavior and high mortality (p < 0.001, median survival: 38 days). Under hypoxia however, dehydroepiandrosterone not only significantly reduced cardiopulmonary remodeling but also remarkably extended survival (p < 0.01, median survival: 126 days). Weight loss and trembling behavior at least partially remained, and polycythemia completely, the latter possibly favorably participating in blood oxygenation. Interestingly, at the dose used, dehydroepiandrosterone sulfate was detrimental to long-term survival in normoxia (p < 0.05, median survival: 147 days).ConclusionDehydroepiandrosterone globally reduced what may be called an age-related frailty induced by hypoxic pulmonary hypertension. This interestingly recalls an inverse correlation found in the prospective PAQUID epidemiological study, between dehydroepiandrosterone blood levels and mortality in aged human smokers and former smokers.

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Advancing front of old-age human survival.

Publications

Advancing front of old-age human survival.

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