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Senescent cell turnover slows with age providing an explanation for the Gompertz law.

ABSTRACT: A causal factor in mammalian aging is the accumulation of senescent cells (SnCs). SnCs cause chronic inflammation, and removing SnCs decelerates aging in mice. Despite their importance, turnover rates of SnCs are unknown, and their connection to aging dynamics is unclear. Here we use longitudinal SnC measurements and induction experiments to show that SnCs turn over rapidly in young mice, with a half-life of days, but slow their own removal rate to a half-life of weeks in old mice. This leads to a critical-slowing-down that generates persistent SnC fluctuations. We further demonstrate that a mathematical model, in which death occurs when fluctuating SnCs cross a threshold, quantitatively recapitulates the Gompertz law of mortality in mice and humans. The model can go beyond SnCs to explain the effects of lifespan-modulating interventions in Drosophila and C. elegans, including scaling of survival-curves and rapid effects of dietary shifts on mortality.

SUBMITTER: Karin O

PROVIDER: S-EPMC6889273 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Senescent cell turnover slows with age providing an explanation for the Gompertz law.

Karin Omer O Agrawal Amit A Porat Ziv Z Krizhanovsky Valery V Alon Uri U

Nature communications 20191202 1

A causal factor in mammalian aging is the accumulation of senescent cells (SnCs). SnCs cause chronic inflammation, and removing SnCs decelerates aging in mice. Despite their importance, turnover rates of SnCs are unknown, and their connection to aging dynamics is unclear. Here we use longitudinal SnC measurements and induction experiments to show that SnCs turn over rapidly in young mice, with a half-life of days, but slow their own removal rate to a half-life of weeks in old mice. This leads to ...[more]

PMID: 31792199

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Project description:BackgroundSelf-explanation without feedback has been shown to improve medical students' diagnostic reasoning. While feedback is generally seen as beneficial for learning, available evidence of the value of its combination with self-explanation is conflicting. This study investigated the effect on medical students' diagnostic performance of adding immediate or delayed content-feedback to self-explanation while solving cases.MethodsNinety-four 3rd-year students from a Canadian medical school were randomly assigned to three experimental conditions (immediate-feedback, delayed-feedback, control). In the learning phase, all students solved four clinical cases by giving i) the most likely diagnosis, ii) two main arguments supporting this diagnosis, and iii) two plausible alternative diagnoses, while using self-explanation. The immediate-feedback group was given the correct diagnosis after each case; delayed-feedback group received the correct diagnoses only after the four cases; control group received no feedback. One week later, all students solved four near-transfer (i.e., same final diagnosis as the learning cases but different scenarios) and four far-transfer cases (i.e., different final diagnosis from the learning cases and different scenarios) by answering the same three questions. Students' diagnostic accuracy (score for the response to the first question only) and diagnostic performance (combined score of responses to the three questions) scores were assessed in each phase. Four one-way ANOVAs were performed on each of the two scores for near and far-transfer cases.ResultsThere was a significant effect of experimental condition on diagnostic accuracy on near-transfer cases (p?<?.05). The immediate-feedback and delayed-feedback groups performed equally well, both better than control (respectively, mean?=?90.73, standard deviation =10.69; mean?=?89.92, standard deviation?=?13.85; mean?=?82.03, standard deviation?=?17.66). The experimental conditions did not significantly differ on far-transfer cases.ConclusionsProviding feedback to students in the form of the correct diagnosis after using self-explanation with clinical cases is potentially beneficial to improve their diagnostic accuracy but this effect is limited to similar cases. Further studies should explore how more elaborated feedback combined with self-explanation may impact students' diagnostic performance on different cases.

Dataset Information

Senescent cell turnover slows with age providing an explanation for the Gompertz law.

Publications

Senescent cell turnover slows with age providing an explanation for the Gompertz law.

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