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

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 agerelated 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 wellestablished effects of exercise in attenuating vascular dysfunction, hypertension, IGF-1 deficiency, and cognitive decline. We highlight here the role of exerciseinduced 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.

Hypertension and Age-Related Cognitive Impairment: Common Risk Factors and a Role for Precision Aging

“…The described vascular health triad-chronic low-grade inflammation, chronic increases in oxidative stress, and hypertension-contributes together to create a feed-forward cascade of continual endothelial dysfunction which feeds the increases in inflammatory cytokines and reactive oxygen damage and chronic hypertension [145]. In addition to the age-related EC senescence and associated inflammatory cascades, age-related hypertension has also been linked to changes in insulin-like growth factor (IGF-1) and microvascular rarefaction [146]. Microvascular rarefaction is the reduction in the number of arteriolar and capillary networks that comprise the resistance vessels in the cerebral cortical vascular bed [147].…”

“…Factors that are known to modulate vascular and endothelial growth and thus vascular rarefaction included vascular endothelial growth factor (VEGF), growth hormone (GH), and insulin-like growth factor-1 (IGF-1). With regard to endothelial cell function and hypertension, IGF-1 has been shown to promote EC cell function and capillary density [ 151 ], [ 36 ••], and an age-related decline in IGF-1 is significantly associated with an increased risk for hypertension [ 146 , 152 ].…”

Beneficial Effect of Ubiquinol on Hematological and Inflammatory Signaling during Exercise

“…There are multiple beneficial effects associated with regular and planned exercise [1,2], including the reduction in the age-related changes in nuclear pore complex proteins, protection of the neuromuscular junction, and the increase in the lives of susceptible motoneurons, preserving neuromuscular integrity and innervation status [3,4]. In addition, exercise increases blood flow and improves vascular integrity, enhancing angiogenesis, resulting in reversal of rarefaction and hypertension, and enhancement of cerebral blood flow and cognition [5].…”

Cathepsin K Deficiency Impaired Ischemia-Induced Neovascularization in Aged Mice

“…On the other hand, recent two comprehensive review articles substantiate the evidence for microvascular contributions to age-related vascular pathobiology that affect microvascular density, and also the recent findings showing the role of exercise in the reversal in microvascular rarefaction is potentially mediated by insulin-like growth factor-1 (IFG-1) [ 35 , 36 ]. Accumulating clinical and laboratory evidence indicate the role of exercise-induced increases in blood flow in improving vascular integrity and stimulating neovascularization via the actions of IGF-1 in aged humans and animals.…”