Young blood-induced rejuvenation of neurovascular coupling involves endothelial IGF-1/IGF-1R signaling: evidence from heterochronic parabiosis using endothelial IGF-1R deficient and systemic IGF-1 knockdown mice.

Rafal Gulej, Roland Patai, Siva Sai Chandragiri, Mark Nagykaldi, Evelyn Brunner, Peter Mukli, Dorina Nagy, Kiana Vali Kordestan, Shoba Ekambaram, Santny Shanmugarama, Raghavendra Yelahanka Nagaraja, Andriy Yabluchanskiy, Stefano Tarantini, Anna Csiszar, Zoltan Ungvari

Vascular Cognitive Impairment, Neurodegeneration, and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. · pubmed

Paper

Abstract

Aging is accompanied by progressive impairment of neurovascular coupling (NVC), the mechanism that matches local cerebral blood flow to neuronal activity, contributing to cognitive decline and the development of vascular cognitive impairment and dementia. Exposure to a young systemic milieu through heterochronic parabiosis has been shown to restore NVC in aged mice, suggesting that circulating factors can rejuvenate cerebrovascular function. Yet, the molecular mediators responsible for this effect remain poorly defined. Building on our long-standing research demonstrating that age-related decline in insulin-like growth factor-1 (IGF-1) signaling contributes to cerebrovascular aging and NVC dysfunction, and on recent transcriptomic evidence implicating IGF-1 receptor (IGF-1R) activation in vascular rejuvenation, we hypothesized that the IGF-1/IGF-1R axis plays a role in the young blood-induced restoration of NVC. To test this, we combined heterochronic parabiosis with two complementary transgenic approaches: systemic IGF-1 knockdown (TBG-Cre-AAV8/Igf1

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Research summary

The paper claims that the IGF-1/IGF-1R signaling pathway mediates the rejuvenating effects of young blood on neurovascular coupling in aged mice. This research addresses the underlying mechanisms of aging and seeks to understand how systemic factors can restore youthful function, which is directly relevant to longevity and age-related diseases.

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