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The role of exercise in the reversal of IGF-1 deficiencies in microvascular rarefaction and hypertension

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Abstract

Hypertension has been linked with peripheral and central reductions in vascular density, and with devastating effects on brain function. However, the underlying mechanisms in the relationship between blood pressure and cognitive impairment have yet to be fully elucidated. Here, we review compelling evidence from two lines of inquiry: one that links microvascular rarefaction with insulin-like growth factor 1 (IGF-1) deficiencies, and another which posits that vascular dysfunction precedes hypertension. Based on the findings from experimental and clinical studies, we propose that these lines of evidence converge, and suggest that age-related declines in IGF-1 concentrations precede microvascular rarefaction, initiate an increase in vascular resistance, and therefore are causally linked to onset of hypertension. Physical exercise provides a relevant model for supporting our premise, given the well-established effects of exercise in attenuating vascular dysfunction, hypertension, IGF-1 deficiency, and cognitive decline. We highlight here the role of exercise-induced increases in blood flow in improving vascular integrity and enhancing angiogenesis via the actions of IGF-1, resulting in reversal of rarefaction and hypertension, and enhancement of cerebral blood flow and cognition.

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Funding

This manuscript was funded in part by the National Institute of General Medical Sciences (NIGMS) 5 T32 GM109780-4 (AMN); National Institute on Aging (NIA) R01AG056769 (TWB); National Heart, Lung, and Blood Institute (NHLBI) 5 T32 HL007457-39 (BK); and The Evelyn F. McKnight Brain Institute at the University of Alabama, Birmingham.

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  1. Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Amani M. Norling, Adam T. Gerstenecker & Ronald M. Lazar

  2. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Thomas W. Buford, Bilal Khan & Suzanne Oparil

  3. The UAB Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Alabama, AL, 35294, USA

    Amani M. Norling, Adam T. Gerstenecker & Ronald M. Lazar

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Conceptualization, literature search, and drafting of the original manuscript (Amani M. Norling). Critical revision for intellectual content (Adam T. Gerstenecker; Thomas W. Buford; Bilal Khan; Suzanne Oparil; Ronald M. Lazar).

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Correspondence to Ronald M. Lazar.

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Norling, A.M., Gerstenecker, A.T., Buford, T.W. et al. The role of exercise in the reversal of IGF-1 deficiencies in microvascular rarefaction and hypertension. GeroScience 42, 141–158 (2020). https://doi.org/10.1007/s11357-019-00139-2

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