Insulin, Aging, and the Brain: Mechanisms and Implications

Akintola, Abimbola A.; Heemst, Diana van

doi:10.3389/fendo.2015.00013

Cited by 97 publications

(74 citation statements)

References 173 publications

(183 reference statements)

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“…It has been shown that insulin controls not only whole-body energy and glucose 50 homeostasis in the periphery of the human body but also exerts specific effects in the (Bhat et al, 2015), which is in accordance 54 with an increase in insulin resistance with age (Akintola and van Heemst, 2015).…”

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confidence: 85%

Buttermilk and Krill Oil Phospholipids Improve Hippocampal Insulin Resistance and Synaptic Signaling in Aged Rats

et al. 2018

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confidence: 85%

Buttermilk and Krill Oil Phospholipids Improve Hippocampal Insulin Resistance and Synaptic Signaling in Aged Rats

et al. 2018

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“…Insulin has neurotransmitter-like functions within the CNS, and insulin receptors are abundant throughout interior brain structures (Adamo et al, 1989; Werner and LeRoith, 2014). Insulin signaling through receptors located within the hippocampus are thought to regulate cognitive processes, while those in the amygdala and other limbic regions have roles in emotion regulation functions (Akintola and van Heemst, 2015). In addition to signaling through insulin receptors, interactions with other neurotransmitter systems can affect emotion regulation and influence behavioral outcomes.…”

Section: Discussionmentioning

confidence: 99%

Metabolic and hormone influences on emotion processing during menopause

Berent-Spillson

Marsh

Persad

et al. 2017

Psychoneuroendocrinology

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Disturbances of emotion regulation and depressive symptoms are common during the menopause transition. Reproductive hormone levels are not directly correlated with depressive symptoms, and other factors may influence mood symptoms during menopause. In this study, we sought to determine the role of metabolic function in mood symptoms during menopause, hypothesizing an association with menopause status and long-term glucose load. We studied 54 women across three menopause transition stages (15 premenopause, 11 perimenopause, and 28 postmenopause), examining effects of age, hormones, and metabolism on mood and neural activation during emotional discrimination. We assessed participants using behavioral and functional MRI measures of negative emotion and emotion discrimination, and glycated hemoglobin A1c, to assess long-term glucose load. We found that emotionally unpleasant images activated emotion regulation (amygdala) and cognitive association brain regions (prefrontal cortex, posterior cingulate, temporal-parietal-occipital (TPO) junction, hippocampus). Cognitive association region activity increased with menopause stage. Perimenopausal women had left TPO junction activation, and postmenopausal women had prefrontal cortex, posterior cingulate, and TPO junction activation. Negative affect was associated with decreased amygdala activation, while depression symptoms and negative mood were associated with increased TPO junction activation. Hemoglobin A1c was associated with negative interpretation bias of neutral images and cognitive region recruitment during emotion discrimination. FSH levels, indicating menopause stage, were associated with negative mood. Age was not associated with any behavioral measures or activation patterns during the emotion task. Our results suggest that an interaction between metabolic and hormonal factors may influence emotion regulation, leading to increased risk for depression during menopause.

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“…Additionally, some of the non-neurological phenotypes enriched for teQTLs, such as insulin sensitivity and inflammation-related traits, suggest that age-dependent genetic control could play a role in traits associated with aging and longevity more generally (Franceschi and Campisi 2014;Akintola and van Heemst 2015).…”

Section: Discussionmentioning

confidence: 99%

Genetic control of age-related gene expression and complex traits in the human brain

Martin

Fraser

2017

Preprint

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Age is the primary risk factor for many of the most common human diseases-particularly neurodegenerative diseases-yet we currently have a very limited understanding of how each individual's genome affects the aging process. Here we introduce a method to map genetic variants associated with age-related gene expression patterns, which we call temporal expression quantitative trait loci (teQTL). We found that these loci are markedly enriched in the human brain and are associated with neurodegenerative diseases such as Alzheimer's disease and Creutzfeldt-Jakob disease. Examining potential molecular mechanisms, we found that agerelated changes in DNA methylation can explain some cis-acting teQTLs, and that trans-acting teQTLs can be mediated by microRNAs. Our results suggest that genetic variants modifying agerelated patterns of gene expression, acting through both cis-and trans-acting molecular mechanisms, could play a role in the pathogenesis of diverse neurological diseases.

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Insulin, Aging, and the Brain: Mechanisms and Implications

Cited by 97 publications

References 173 publications

Buttermilk and Krill Oil Phospholipids Improve Hippocampal Insulin Resistance and Synaptic Signaling in Aged Rats

Buttermilk and Krill Oil Phospholipids Improve Hippocampal Insulin Resistance and Synaptic Signaling in Aged Rats

Metabolic and hormone influences on emotion processing during menopause

Genetic control of age-related gene expression and complex traits in the human brain

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