Age-related decline in circulating IGF-1 associates with impaired neurovascular coupling responses in older adults

Geroscience. 2022 Dec;44(6):2771-2783. doi: 10.1007/s11357-022-00623-2. Epub 2022 Jul 23.

Abstract

Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) to the increased oxygen and energy requirements of active brain regions via neurovascular coupling (NVC) contributes to the genesis of age-related cognitive impairment. Aging is associated with marked deficiency in the vasoprotective hormone insulin-like growth factor-1 (IGF-1). Preclinical studies on animal models of aging suggest that circulating IGF-1 deficiency is causally linked to impairment of NVC responses. The present study was designed to test the hypotheses that decreases in circulating IGF-1 levels in older adults also predict the magnitude of age-related decline of NVC responses. In a single-center cross-sectional study, we enrolled healthy young (n = 31, 11 female, 20 male, mean age: 28.4 + / - 4.2 years) and aged volunteers (n = 32, 18 female, 14 male, mean age: 67.9 + / - 4.1 years). Serum IGF-1 level, basal CBF (phase contrast magnetic resonance imaging (MRI)), and NVC responses during the trail making task (with transcranial Doppler sonography) were assessed. We found that circulating IGF-1 levels were significantly decreased with age and associated with decreased basal CBF. Age-related decline in IGF-1 levels predicted the magnitude of age-related decline in NVC responses. In conclusion, our study provides additional evidence in support of the concept that age-related circulating IGF-1 deficiency contributes to neurovascular aging, impairing CBF and functional hyperemia in older adults.

Keywords: Aging; Cognitive decline; Neurovascular uncoupling; VCI; VCID; Vascular cognitive impairment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cerebrovascular Circulation / physiology
  • Cross-Sectional Studies
  • Female
  • Insulin-Like Growth Factor I
  • Male
  • Neurovascular Coupling* / physiology

Substances

  • Insulin-Like Growth Factor I

Supplementary concepts

  • Insulin-Like Growth Factor I Deficiency