Senolytic CAR T cells reverse aging-associated defects in intestinal regeneration and fitness

Eskiocak, Onur, Chowdhury, Saria, Shah, Vyom, Nnuji-John, Emmanuella, Chung, Charlie, Boyer, Jacob A, Harris, Alexander S, Habel, Jill, Sadelain, Michel, Beyaz, Semir, Amor, Corina (March 2024) Senolytic CAR T cells reverse aging-associated defects in intestinal regeneration and fitness. bioRxiv. (Submitted)

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Abstract

Intestinal stem cells (ISCs) drive the rapid regeneration of the gut epithelium to maintain organismal homeostasis. Aging, however, significantly reduces intestinal regenerative capacity. While cellular senescence is a key feature of the aging process, little is known about the in vivo effects of senescent cells on intestinal fitness. Here, we identify the accumulation of senescent cells in the aging gut and, by harnessing senolytic CAR T cells to eliminate them, we uncover their detrimental impact on epithelial integrity and overall intestinal homeostasis in natural aging, injury and colitis. Ablation of intestinal senescent cells with senolytic CAR T cells in vivo or in vitro is sufficient to promote the regenerative potential of aged ISCs. This intervention improves epithelial integrity and mucosal immune function. Overall, these results highlight the ability of senolytic CAR T cells to rejuvenate the intestinal niche and demonstrate the potential of targeted cell therapies to promote tissue regeneration in aging organisms.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
CSHL Authors:	Eskiocak, Onur Nnuji-John, Emmanuella Chung, Charlie Habel, Jill Beyaz, Semir Chowdhury, Saria Shah, Vyom Amor, Corina Harris, Alexander
Communities:	CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Flow Cytometry Service CSHL Cancer Center Shared Resources > Histology Service CSHL Cancer Center Shared Resources > Organoid Service CSHL Cancer Center Shared Resources > Single-Cell Biology Service CSHL labs > Beyaz lab CSHL labs > Meyer Lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	22 March 2024
Date Deposited:	27 Mar 2024 16:10
Last Modified:	29 Apr 2024 15:35
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41480

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