학술논문

Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain
Document Type
article
Source
EMBO Molecular Medicine, Vol 15, Iss 5, Pp n/a-n/a (2023)
Subject
Aging
Brain
Gene Therapy
Interleukin 2
Regulatory T cells
Medicine (General)
R5-920
Genetics
QH426-470
Language
English
ISSN
1757-4684
1757-4676
Abstract
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.