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

Eskiocak, O.; Chowdhury, S.; Shah, V.; Nnuji-John, E.; Chung, C.; Boyer, J. A.; Harris, A. S.; Habel, J.; Sadelain, M.; Beyaz, S.; Amor, C.

2024-03-22 cell biology
10.1101/2024.03.19.585779 bioRxiv
Show 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.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

1
Nature Aging
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Top 0.1%
18.9%
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2
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11.3%
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5
Cell Metabolism
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6
eLife
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Top 25%
4.9%
7
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○ 165 papers in training set
Top 0.7%
4.9%
8
Developmental Cell
○ 196 papers in training set
Top 2%
2.4%
9
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 26%
1.8%
10
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○ 67 papers in training set
Top 1.0%
1.7%
11
Nature Cell Biology
○ 118 papers in training set
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1.7%
12
iScience
○ 1154 papers in training set
Top 18%
1.7%
13
Cell Reports Medicine
○ 153 papers in training set
Top 3%
1.5%
14
Nature Medicine
○ 125 papers in training set
Top 2%
1.5%
15
Nature
○ 645 papers in training set
Top 8%
1.4%
16
The EMBO Journal
○ 309 papers in training set
Top 4%
1.4%
17
JCI Insight
● 277 papers in training set
Top 5%
1.2%
18
Cell Death & Differentiation
○ 48 papers in training set
Top 0.8%
1.2%
19
npj Regenerative Medicine
○ 24 papers in training set
Top 0.5%
1.2%
20
Science Advances
● 1243 papers in training set
Top 24%
1.2%
21
Science
● 477 papers in training set
Top 7%
1.1%
22
GeroScience
○ 109 papers in training set
Top 2%
0.9%
23
Cellular and Molecular Gastroenterology and Hepatology
○ 46 papers in training set
Top 0.9%
0.9%
24
Molecular Cell
○ 350 papers in training set
Top 5%
0.9%
25
Nature Metabolism
○ 69 papers in training set
Top 2%
0.9%
26
Cell
○ 431 papers in training set
Top 10%
0.9%
27
EMBO Reports
○ 263 papers in training set
Top 8%
0.6%
28
Stem Cell Reports
○ 130 papers in training set
Top 2%
0.6%
29
Communications Biology
○ 993 papers in training set
Top 33%
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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.