2022
DOI: 10.1101/2022.05.10.491392
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Accelerating the clock: Interconnected speedup of energetic and molecular dynamics during aging in cultured human cells

Abstract: The allometric theory of metabolism predicts that the rate of biological aging is proportional to an organism’s size and metabolic rate (MR). Here we test this hypothesis in humans by generating longitudinal, multi-modal signatures of aging in primary human fibroblasts. Relative to metabolic rates in the human body, isolated cells exhibit markedly elevated MR and operate closer to their maximal energy production capacity. Accordingly, per-cell division, isolated cells display accelerated telomere shortening an… Show more

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Cited by 5 publications
(2 citation statements)
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“…Here, we generated a longitudinal DNA methylation dataset using the EPIC array ( Sturm et al, 2022 ), and deployed an approach that increases DNAmAge accuracy using a principal component-adjustment of the classic epigenetic clocks ( Higgins-Chen et al, 2022 ). The difference between the initial epigenetic age of the donors and their chronological age at the time of the biopsy can be explained the variable time and/or cell divisions underwent by each cell line before the beginning of the experiments, and because cells cultured in vitro experience an accelerated epigenetic aging rate compared to in vivo conditions ( Sturm et al, 2019 , 2023b ). Regardless of the estimated initial epigenetic age, by applying the clocks across the cellular lifespan, we can longitudinally quantify the rate of epigenetic aging relative to population doublings.…”
Section: Resultsmentioning
confidence: 99%
“…Here, we generated a longitudinal DNA methylation dataset using the EPIC array ( Sturm et al, 2022 ), and deployed an approach that increases DNAmAge accuracy using a principal component-adjustment of the classic epigenetic clocks ( Higgins-Chen et al, 2022 ). The difference between the initial epigenetic age of the donors and their chronological age at the time of the biopsy can be explained the variable time and/or cell divisions underwent by each cell line before the beginning of the experiments, and because cells cultured in vitro experience an accelerated epigenetic aging rate compared to in vivo conditions ( Sturm et al, 2019 , 2023b ). Regardless of the estimated initial epigenetic age, by applying the clocks across the cellular lifespan, we can longitudinally quantify the rate of epigenetic aging relative to population doublings.…”
Section: Resultsmentioning
confidence: 99%
“…On the other hand, our longitudinal in vitro studies allows us to measure Numts among the same cell population (i.e., "individual") over time as cells accumulate age-related molecular changes. In this system, cells divide approximately every 40 hours (1.7 days) when they are young (from days 0-80) and slow their replication rate dramatically towards the end of life, when they undergo less than one replicative event per month (see growth curves in (81)). Although the temporal resolution of our trajectories is limited by the number of timepoints across the lifespan of each cell line (on average 7), our data suggests that the rate of numtogenesis is roughly linear across the wide range of replication rate, and therefore more dependent on time rather than the rate of replication.…”
Section: Discussionmentioning
confidence: 99%