TY - JOUR
T1 - 40 years of IGF1
T2 - IGF1: The Jekyll and Hyde of the aging brain
AU - Gubbi, Sriram
AU - Quipildor, Gabriela Farias
AU - Barzilai, Nir
AU - Huffman, Derek M.
AU - Milman, Sofiya
N1 - Publisher Copyright:
© 2018 Society for Endocrinology Published by Bioscientifica Ltd.
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
KW - Alzheimer’s
KW - CNS
KW - Cognition
KW - Parkinson’s
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U2 - 10.1530/JME-18-0093
DO - 10.1530/JME-18-0093
M3 - Review article
C2 - 29739805
AN - SCOPUS:85051084343
SN - 0952-5041
VL - 61
SP - T171-T185
JO - Journal of Molecular Endocrinology
JF - Journal of Molecular Endocrinology
IS - 1
ER -