Counting Cells by Age Tells Us About How, and Why, and When, We Grow, and Become Old and Ill

medrxiv(2023)

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摘要
Growth and aging are fundamental features of animal life. The march from fertilization to oblivion comes in enormous variety: days and hundreds of cells for nematodes, decades and trillions of cells for humans.[1][1]-[4][2] Since Verhulst (1838[5][3]) proposed the Logistic Equation - exponential growth with a countervailing linear decline in rate – biologists have searched for ever better density-dependent growth equations,[6][4]-[12][5] none of which accurately capture the relationship between size and time for real animals.[13][6]-[15][7] Furthermore, while growth and aging run in parallel, whether the relationship is causal has yet to be determined. Similarly unknown has been the reason behind the exponential Force of Mortality , described by Gompertz in 1825 for all-cause mortality[16][8] and reported by Levin et al. in 2020 for COVID-19.[17][9] Here we report that examination in units of numbers of cells, N, Cellular Phylodynamic Analysis ,[6][4] reveals that growth, lifespan, and mortality, are linked to the reduction in the fraction of cells dividing, occurring by a simple expression, the Universal Mitotic Fraction Equation . Lifespan is correlated with an age when fewer than one-in-a-thousand cells are dividing, quantifying the long-appreciated mechanism of aging, the failure of cells to be rejuvenated by dilution with new materials made and DNA repaired at mitosis.[29][10]-[31][11] These observations provide practical mathematical tools for comprehending and managing the challenges of growth and aging, for such tasks as deciphering COVID-19 lethality and its amelioration by vaccination. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No Funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All raw data in this paper was taken from other studies, and is readily available from those studies, which have been cited. [1]: #ref-1 [2]: #ref-4 [3]: #ref-5 [4]: #ref-6 [5]: #ref-12 [6]: #ref-13 [7]: #ref-15 [8]: #ref-16 [9]: #ref-17 [10]: #ref-29 [11]: #ref-31
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cells,age tells us,old
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