Theory Article Volume 12, Issue 11 pp 11152—11160
LSEC model of aging
- 1 Institute for Research on Cancer and Aging of Nice (IRCAN), INSERM, Université Côte d’Azur, CNRS, Nice, France
Received: May 18, 2020 Accepted: June 5, 2020 Published: June 13, 2020https://doi.org/10.18632/aging.103492
How to Cite
Copyright © 2020 Grosse et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data obtained from genetically modified mouse models suggest a detrimental role for p16High senescent cells in physiological aging and age-related pathologies. Our recent analysis of aging mice revealed a continuous and noticeable accumulation of liver sinusoid endothelial cells (LSECs) expressing numerous senescence markers, including p16. At early stage, senescent LSECs show an enhanced ability to clear macromolecular waste and toxins including oxidized LDL (oxLDL). Later in life, however, the efficiency of this important detoxifying function rapidly declines potentially due to increased endothelial thickness and senescence-induced silencing of scavenger receptors and endocytosis genes. This inability to detoxify toxins and macromolecular waste, which can be further exacerbated by increased intestinal leakiness with age, might be an important contributing factor to animal death. Here, we propose how LSEC senescence could serve as an endogenous clock that ultimately controls longevity and outline some of the possible approaches to extend the lifespan.