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Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain.

ABSTRACT: Cognitive decline is a common pathological outcome during aging, with an ill-defined molecular and cellular basis. In recent years, the concept of inflammaging, defined as a low-grade inflammation increasing with age, has emerged. Infiltrating T cells accumulate in the brain with age and may contribute to the amplification of inflammatory cascades and disruptions to the neurogenic niche observed with age. Recently, a small resident population of regulatory T cells has been identified in the brain, and the capacity of IL2-mediated expansion of this population to counter neuroinflammatory disease has been demonstrated. Here, we test a brain-specific IL2 delivery system for the prevention of neurological decline in aging mice. We identify the molecular hallmarks of aging in the brain glial compartments and identify partial restoration of this signature through IL2 treatment. At a behavioral level, brain IL2 delivery prevented the age-induced defect in spatial learning, without improving the general decline in motor skill or arousal. These results identify immune modulation as a potential path to preserving cognitive function for healthy aging.

SUBMITTER: Lemaitre P

PROVIDER: S-EPMC10165365 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain.

Lemaitre Pierre P Tareen Samar Hk SH Pasciuto Emanuela E Mascali Loriana L Martirosyan Araks A Callaerts-Vegh Zsuzsanna Z Poovathingal Suresh S Dooley James J Holt Matthew G MG Yshii Lidia L Liston Adrian A

EMBO molecular medicine 20230328 5

Cognitive decline is a common pathological outcome during aging, with an ill-defined molecular and cellular basis. In recent years, the concept of inflammaging, defined as a low-grade inflammation increasing with age, has emerged. Infiltrating T cells accumulate in the brain with age and may contribute to the amplification of inflammatory cascades and disruptions to the neurogenic niche observed with age. Recently, a small resident population of regulatory T cells has been identified in the brai ...[more]

PMID: 36975362

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Dataset Information

Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain.

Publications

Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain.

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