Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

No Time to Age: Uncoupling Aging from Chronological Time

Version 1 : Received: 13 April 2021 / Approved: 14 April 2021 / Online: 14 April 2021 (14:15:26 CEST)

A peer-reviewed article of this Preprint also exists.

Larocca, D.; Lee, J.; West, M.D.; Labat, I.; Sternberg, H. No Time to Age: Uncoupling Aging from Chronological Time. Genes 2021, 12, 611. Larocca, D.; Lee, J.; West, M.D.; Labat, I.; Sternberg, H. No Time to Age: Uncoupling Aging from Chronological Time. Genes 2021, 12, 611.

Journal reference: Genes 2021, 12, 611
DOI: 10.3390/genes12050611

Abstract

Multicellular life evolved from simple unicellular organisms that could replicate indefinitely being essentially ageless. At this point, life split into 2 fundamentally different cell types: the immortal germline representing an unbroken lineage of cell division with no intrinsic endpoint and the mortal soma which ages and dies. In this review, we describe the germline as clock-free and the soma as clock-bound and discuss aging with respect to 3 DNA-based cellular clocks (telomeric, DNA methylation, and transposable element). The ticking of these clocks corresponds to the stepwise progressive limitation of growth and regeneration of somatic cells that we term, somatic restriction. Somatic restriction acts in opposition to strategies that ensure continued germline replication and regeneration. We thus consider the plasticity of aging as a process not fixed to the pace of chronological time but one that can speed up or slow down depending on the rate of intrinsic cellular clocks. We further describe how germline factor reprogramming might be used to slow the rate of aging and potentially reverse it by causing the clocks to tick backwards. Therefore, reprogramming may eventually lead to therapeutic strategies to treat degenerative diseases by altering aging itself, the one condition common to us all.

Subject Areas

Aging; cellular clocks; reprogramming; development; epigenetics; DNA methylation; telomeres; transposable elements; longevity; regeneration

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