GEO series
P21+TREM2+-Senescent Macrophages Fuel Inflammaging and Metabolic Dysfunction-Associated Steatotic Liver Disease [NAFLD_time_course]
GSE319035
Mus musculus
Expression profiling by high throughput sequencing
77 samples
Submitted 2026/02/16
Platform GPL34290
Summary
Cellular senescence drives chronic sterile inflammation during aging via the senescence-associated secretory phenotype (SASP); however, the cell types responsible for this pathology remain poorly defined. Here, we identify p21⁺Trem2⁺ senescent macrophages as a major source of inflammaging. Using primary mouse and human macrophages, we developed a model of DNA damage and cholesterol-induced senescence and applied multi-omic profiling to fully characterize senescent macrophages. We found that senescent macrophages exhibit a distinctive p21-TREM2 expression profile and SASP, driven in part by type-I interferon signaling via secreted mitochondrial DNA. We also found that senescent macrophage accumulation occurs in aged and MASLD mouse livers and is enriched in human cirrhotic liver tissue. Finally, senolytic treatment targeting senescent macrophages reduced liver inflammation and steatosis in both aged and MASLD mice. Together, these findings establish macrophage senescence as a central driver of chronic inflammation in aging and metabolic liver disease, highlighting a promising, tractable therapeutic target.
Published in
Salladay-Perez IA, Avila I, Estrada L et al.
· Nature aging 2026
· PMID 41991686
· doi:10.1038/s43587-026-01101-6
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE319035_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 77 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1422001 and SRA study SRP676109. Searching any of these in the dataset finder brings you back here.
Study design
40 conditions, each sampled once — no replicated groups
Read from the first 40 of 77 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9508397 SH1_C57BL6J_0week_chow
- GSM9508398 SH2_C57BL6J_0week_chow
- GSM9508399 SH3_C57BL6J_0week_chow
- GSM9508400 SH4_C57BL6J_2week_ath
- GSM9508401 SH5_C57BL6J_2week_ath
- GSM9508402 SH6_C57BL6J_2week_ath
- GSM9508403 SH7_C57BL6J_4week_ath
- GSM9508404 SH8_C57BL6J_4week_ath
- GSM9508405 SH9_C57BL6J_4week_ath
- GSM9508406 SH10_C57BL6J_8week_ath
- GSM9508407 SH11_C57BL6J_8week_ath
- GSM9508408 SH12_C57BL6J_8week_ath
- GSM9508409 SH13_C57BL6J_12week_ath
- GSM9508410 SH14_C57BL6J_12week_ath
- GSM9508411 SH15_C57BL6J_12week_ath
- GSM9508412 SH16_C57BL6J_16week_ath
- GSM9508413 SH17_C57BL6J_16week_ath
- GSM9508414 SH18_C57BL6J_16week_ath
- GSM9508415 SH19_C57BL6J_16week_chow
- GSM9508416 SH20_C57BL6J_16week_chow
- GSM9508417 SH21_C57BL6J_16week_chow
- GSM9508418 SH22_BXD19_0week_chow
- GSM9508419 SH23_BXD19_0week_chow
- GSM9508420 SH24_BXD19_0week_chow
- GSM9508421 SH25_BXD19_0week_chow
- GSM9508422 SH26_BXD19_2week_ath
- GSM9508423 SH27_BXD19_2week_ath
- GSM9508424 SH28_BXD19_2week_ath
- GSM9508425 SH29_BXD19_2week_ath
- GSM9508426 SH30_BXD19_4week_ath
- GSM9508427 SH31_BXD19_4week_ath
- GSM9508428 SH32_BXD19_4week_ath
- GSM9508429 SH33_BXD19_4week_ath
- GSM9508430 SH34_BXD19_8week_ath
- GSM9508431 SH35_BXD19_8week_ath
- GSM9508432 SH36_BXD19_8week_ath
- GSM9508433 SH37_BXD19_8week_ath
- GSM9508434 SH38_BXD19_12week_ath
- GSM9508435 SH39_BXD19_12week_ath
- GSM9508436 SH40_BXD19_12week_ath
+ 37 more — browse all 77 samples with per-sample file links →
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