biostudies-literatureGoldberg ELNIA NIH HHSNIDDK NIH HHSCure Alzheimer's FundNational Institutes of HealthNIAMS NIH HHSNational Institute on AgingJapan Society for the Promotion of Science2277-2287.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC9067336biostudies-literatureUnknown33(11)Aging impairs the integrated immunometabolic responses, which have evolved to maintain core body temperature in homeotherms to survive cold stress, infections, and dietary restriction. Adipose tissue inflammation regulates the thermogenic stress response, but how adipose tissue-resident cells instigate thermogenic failure in the aged are unknown. Here, we define alterations in the adipose-resident immune system and identify that type 2 innate lymphoid cells (ILC2s) are lost in aging. Restoration of ILC2 numbers in aged mice to levels seen in adults through IL-33 supplementation failed to rescue old mice from metabolic impairment and increased cold-induced lethality. Transcriptomic analyses revealed intrinsic defects in aged ILC2, and adoptive transfer of adult ILC2s are sufficient to proteCell metabolismIL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2.PMC9067336R01 AG068863AR070811R00AG058801P01 AG051459P01AG051459R00 AG058801AG068863R01 AR070811P30 DK056341Young KCDixit VDShchukina IGoldberg ELTsusaka TCamell CDDlugos TYoum YHArtyomov MNRyu SfalseIL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2.Aging impairs the integrated immunometabolic responses, which have evolved to maintain core body temperature in homeotherms to survive cold stress, infections, and dietary restriction. Adipose tissue inflammation regulates the thermogenic stress response, but how adipose tissue-resident cells instigate thermogenic failure in the aged are unknown. Here, we define alterations in the adipose-resident immune system and identify that type 2 innate lymphoid cells (ILC2s) are lost in aging. Restoration of ILC2 numbers in aged mice to levels seen in adults through IL-33 supplementation failed to rescue old mice from metabolic impairment and increased cold-induced lethality. Transcriptomic analyses revealed intrinsic defects in aged ILC2, and adoptive transfer of adult ILC2s are sufficient to prote2021-01-01T00:00:00Z2021 Nov2026-05-09T19:29:57.804Z2025-04-19T22:48:00.31ZS-EPMC90673363447395610.1016/j.cmet.2021.08.004