Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review

Frater, Julanne; Lie, David; Bartlett, Perry F.; McGrath, John J.

doi:10.1016/j.arr.2017.12.002

Cited by 67 publications

(36 citation statements)

References 136 publications

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“…Age-related cognitive decline, which in its more progressive forms, may be characterized by mild cognitive impairment (MCI) or dementia, secondary to causes such as cerebrovascular ischemia or Alzheimer’s disease (AD), poses a significant burden for an increasingly aging population, raising the urgency to identify underlying contributors to these conditions in order to delay or prevent their onset (Langa, et al 2017; Prince, et al 2016; Wu, et al 2017). Studies in humans and rodents have been conducted into the possible relationship between IGF-1 and the cognitive domain, and have uncovered interesting, albeit at times conflicting associations (Frater, et al 2017). A number of cross-sectional studies in middle and older age adults have revealed a positive correlation between IGF-1 levels and cognition (Al-Delaimy, et al 2009; Doi, et al 2015; Wennberg, et al 2018).…”

Section: Igf-1 and Cognitionmentioning

confidence: 99%

40 YEARS of IGF1: IGF1: the Jekyll and Hyde of the aging brain

Gubbi

Quipildor

Barzilai

et al. 2018

Journal of Molecular Endocrinology

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The insulin-like growth factor 1 (IGF1) signaling pathway has emerged as a major regulator of the aging process, from rodents to humans. However, given the pleiotropic actions of IGF1, its role in the aging brain remains complex and controversial. While IGF1 is clearly essential for normal development of the central nervous system, conflicting evidence has emerged from preclinical and human studies regarding its relationship to cognitive function, as well as cerebrovascular and neurodegenerative disorders. This review delves into the current state of the evidence examining the role of IGF1 in the aging brain, encompassing preclinical and clinical studies. A broad examination of the data indicates that IGF1 may indeed play opposing roles in the aging brain, depending on the underlying pathology and context. Some evidence suggests that in the setting of neurodegenerative diseases that manifest with abnormal protein deposition in the brain, such as Alzheimer's disease, reducing IGF1 signaling may serve a protective role by slowing disease progression and augmenting clearance of pathologic proteins to maintain cellular homeostasis. In contrast, inducing IGF1 deficiency has also been implicated in dysregulated function of cognition and the neurovascular system, suggesting that some IGF1 signaling may be necessary for normal brain function. Furthermore, states of acute neuronal injury, which necessitate growth, repair and survival signals to persevere, typically demonstrate salutary effects of IGF1 in that context. Appreciating the dual, at times opposing 'Dr Jekyll' and 'Mr Hyde' characteristics of IGF1 in the aging brain, will bring us closer to understanding its impact and devising more targeted IGF1-related interventions.

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Section: Igf-1 and Cognitionmentioning

confidence: 99%

40 YEARS of IGF1: IGF1: the Jekyll and Hyde of the aging brain

Gubbi

Quipildor

Barzilai

et al. 2018

Journal of Molecular Endocrinology

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“…In fact, in some experiments, the overexpression of IGF-1 reduces cardiomyocytes death and prevents hypertrophy after acute myocardial infarction [ 212 ]. In another experimental series, long term exposure of cardiac tissue to IGF-1, leads to heart failure after cardiac ischemia/reperfusion [ 213 , 214 ]. Based on these data, IGF-1 exerts different effects based on the time of exposure and on the paracrine effects of IGF-1.…”

Section: Genetic Impact On Agingmentioning

confidence: 99%

The Impact of Aging on Cardio and Cerebrovascular Diseases

Izzo

Carrizzo

Alfano

et al. 2018

IJMS

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A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to elaborate the best therapeutic strategy to adopt, without neglecting all the risk factors associated with advanced age. Of course, the better way should always be understanding risk-to-benefit ratio, maintenance of independence and reduction of symptoms. Although improvements in treatment of cardiovascular diseases in the elderly population have increased the survival rate, several studies are needed to understand the best management option to improve therapeutic outcomes. The aim of this review is to give a 360° panorama on what goes on in the fragile ecosystem of elderly, why it happens and what we can do, right now, with the tools at our disposal to slow down aging, until new discoveries on aging, cardio and cerebrovascular diseases are at hand.

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“…In humans, IGF-1 levels are positively related to hippocampal volume and memory (Maass et al 2016). Higher IGF-1 levels in elderly subjects are associated with better cognitive function, whereas low IGF-1 levels are associated with cognitive impairment (Doi et al 2015;Frater et al 2018;Landi et al 2007;Rollero et al 1998), Alzheimer's disease, and vascular dementia (Quinlan et al 2017;Watanabe et al 2005).…”

Section: The Role Of Igf-1 In Rarefactionmentioning

confidence: 99%

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

et al. 2019

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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.

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Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review

Cited by 67 publications

References 136 publications

40 YEARS of IGF1: IGF1: the Jekyll and Hyde of the aging brain

40 YEARS of IGF1: IGF1: the Jekyll and Hyde of the aging brain

The Impact of Aging on Cardio and Cerebrovascular Diseases

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

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