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The impact of dietary energy intake on cognitive aging.

Mattson MP - Front Aging Neurosci (2010)

Bottom Line: Our findings from studies of animal models suggest that dietary energy restriction can enhance neural plasticity and reduce the vulnerability of the brain to age-related dysfunction and disease.Dietary energy restriction may exert beneficial effects on the brain by engaging adaptive cellular stress response pathways resulting in the up-regulation of genes that encode proteins that promote neural plasticity and cell survival (e.g., neurotrophic factors, protein chaperones and redox enzymes).Alternate day calorie restriction, novel insulin-sensitizing and neuroprotective agents, and drugs that activate adaptive stress response pathways, are examples of approaches for preserving cognitive function that show promise in preclinical studies.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program Baltimore, MD, USA.

ABSTRACT
Rodents that are insulin resistant and obese as the result of genetic factors, overeating and/or a sedentary lifestyle, exhibit cognitive deficits that worsen with advancing age compared to their more svelte counterparts. Data from epidemiological and clinical studies suggest similar adverse effects of excessive dietary energy intake and insulin resistance on cognition in humans. Our findings from studies of animal models suggest that dietary energy restriction can enhance neural plasticity and reduce the vulnerability of the brain to age-related dysfunction and disease. Dietary energy restriction may exert beneficial effects on the brain by engaging adaptive cellular stress response pathways resulting in the up-regulation of genes that encode proteins that promote neural plasticity and cell survival (e.g., neurotrophic factors, protein chaperones and redox enzymes). Two energy state-sensitive factors that are proving particularly important in regulating energy balance and improving/preserving cognitive function are brain-derived neurotrophic factor and glucagon-like peptide 1. Alternate day calorie restriction, novel insulin-sensitizing and neuroprotective agents, and drugs that activate adaptive stress response pathways, are examples of approaches for preserving cognitive function that show promise in preclinical studies.

No MeSH data available.


Related in: MedlinePlus

Hormetic mechanism of action of dietary energy restriction. A mild cellular stress occurs in neurons during periods of dietary energy restriction or vigorous physical exercise; this may result from increased electrical/synaptic activity and/or an energetic deficit. Adaptive cellular stress response signaling pathways are activated in brain cells including those that induce the expression of neurotrophic factors, protein chaperones and antioxidant enzymes. In this way, dietary energy restriction and exercise protect cells against oxidative and metabolic stress, and prevent the accumulation of damaged proteins, DNA and membranes in neurons. The increased survival and plasticity of brain cells is the reason why dietary moderation and exercise promote healthy brain aging.
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Figure 2: Hormetic mechanism of action of dietary energy restriction. A mild cellular stress occurs in neurons during periods of dietary energy restriction or vigorous physical exercise; this may result from increased electrical/synaptic activity and/or an energetic deficit. Adaptive cellular stress response signaling pathways are activated in brain cells including those that induce the expression of neurotrophic factors, protein chaperones and antioxidant enzymes. In this way, dietary energy restriction and exercise protect cells against oxidative and metabolic stress, and prevent the accumulation of damaged proteins, DNA and membranes in neurons. The increased survival and plasticity of brain cells is the reason why dietary moderation and exercise promote healthy brain aging.

Mentions: To elucidate the influence of dietary energy restriction on cognitive function, we tested the effects of long-term controlled daily CR (40% reduction in calories) and ADF on learning and memory in 3 × TgAD mice, an animal model of Alzheimer's disease (Halagappa et al., 2007). 3 × TgAD mice develop progressive accumulation of amyloid β-peptide in their hippocampus and cerebral cortex, tau pathology in CA1 hippocampal neurons, and impaired hippocampal synaptic plasticity (Oddo et al., 2003). Beginning at 5 months of age we maintained groups of 3 × TgAD mice on the usual ad libitum control diet, the 40% CR diet or the ADF diet for 12 months. As reference controls, we also included in the study a group of non-transgenic mice maintained on an ad libitum diet. The 3 × TgAD mice on the ad libitum diet exhibit impaired learning and memory in the water maze compared to non-transgenic mice, and both the CR and ADF diets ameliorated the cognitive deficit in the 3 × TgAD mice (Halagappa et al., 2007). We found that 3 × TgAD mice on the CR diet exhibited reduced levels of amyloid β-peptide and hyperphosphorylated tau in their hippocampus compared to 3 × TgAD mice on the ad libitum diet. Interestingly, however, the ADF diet did not lessen the amyloid or tau pathologies. We hypothesize that, by activating adaptive cellular stress response pathways (BDNF, protein chaperones, etc.), ADF preserves synaptic function even in the presence of considerable amyloid and tau pathology (Figure 2). Consistent with this hypothesis, Qin et al. (2008) found that the transcription factor FOXO3a (which is known to mediate adaptive responses of neurons to stress) is involved in the mechanism by which CR suppresses amyloid pathology and memory deficits in a mouse model of Alzheimer's disease.


The impact of dietary energy intake on cognitive aging.

Mattson MP - Front Aging Neurosci (2010)

Hormetic mechanism of action of dietary energy restriction. A mild cellular stress occurs in neurons during periods of dietary energy restriction or vigorous physical exercise; this may result from increased electrical/synaptic activity and/or an energetic deficit. Adaptive cellular stress response signaling pathways are activated in brain cells including those that induce the expression of neurotrophic factors, protein chaperones and antioxidant enzymes. In this way, dietary energy restriction and exercise protect cells against oxidative and metabolic stress, and prevent the accumulation of damaged proteins, DNA and membranes in neurons. The increased survival and plasticity of brain cells is the reason why dietary moderation and exercise promote healthy brain aging.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874403&req=5

Figure 2: Hormetic mechanism of action of dietary energy restriction. A mild cellular stress occurs in neurons during periods of dietary energy restriction or vigorous physical exercise; this may result from increased electrical/synaptic activity and/or an energetic deficit. Adaptive cellular stress response signaling pathways are activated in brain cells including those that induce the expression of neurotrophic factors, protein chaperones and antioxidant enzymes. In this way, dietary energy restriction and exercise protect cells against oxidative and metabolic stress, and prevent the accumulation of damaged proteins, DNA and membranes in neurons. The increased survival and plasticity of brain cells is the reason why dietary moderation and exercise promote healthy brain aging.
Mentions: To elucidate the influence of dietary energy restriction on cognitive function, we tested the effects of long-term controlled daily CR (40% reduction in calories) and ADF on learning and memory in 3 × TgAD mice, an animal model of Alzheimer's disease (Halagappa et al., 2007). 3 × TgAD mice develop progressive accumulation of amyloid β-peptide in their hippocampus and cerebral cortex, tau pathology in CA1 hippocampal neurons, and impaired hippocampal synaptic plasticity (Oddo et al., 2003). Beginning at 5 months of age we maintained groups of 3 × TgAD mice on the usual ad libitum control diet, the 40% CR diet or the ADF diet for 12 months. As reference controls, we also included in the study a group of non-transgenic mice maintained on an ad libitum diet. The 3 × TgAD mice on the ad libitum diet exhibit impaired learning and memory in the water maze compared to non-transgenic mice, and both the CR and ADF diets ameliorated the cognitive deficit in the 3 × TgAD mice (Halagappa et al., 2007). We found that 3 × TgAD mice on the CR diet exhibited reduced levels of amyloid β-peptide and hyperphosphorylated tau in their hippocampus compared to 3 × TgAD mice on the ad libitum diet. Interestingly, however, the ADF diet did not lessen the amyloid or tau pathologies. We hypothesize that, by activating adaptive cellular stress response pathways (BDNF, protein chaperones, etc.), ADF preserves synaptic function even in the presence of considerable amyloid and tau pathology (Figure 2). Consistent with this hypothesis, Qin et al. (2008) found that the transcription factor FOXO3a (which is known to mediate adaptive responses of neurons to stress) is involved in the mechanism by which CR suppresses amyloid pathology and memory deficits in a mouse model of Alzheimer's disease.

Bottom Line: Our findings from studies of animal models suggest that dietary energy restriction can enhance neural plasticity and reduce the vulnerability of the brain to age-related dysfunction and disease.Dietary energy restriction may exert beneficial effects on the brain by engaging adaptive cellular stress response pathways resulting in the up-regulation of genes that encode proteins that promote neural plasticity and cell survival (e.g., neurotrophic factors, protein chaperones and redox enzymes).Alternate day calorie restriction, novel insulin-sensitizing and neuroprotective agents, and drugs that activate adaptive stress response pathways, are examples of approaches for preserving cognitive function that show promise in preclinical studies.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program Baltimore, MD, USA.

ABSTRACT
Rodents that are insulin resistant and obese as the result of genetic factors, overeating and/or a sedentary lifestyle, exhibit cognitive deficits that worsen with advancing age compared to their more svelte counterparts. Data from epidemiological and clinical studies suggest similar adverse effects of excessive dietary energy intake and insulin resistance on cognition in humans. Our findings from studies of animal models suggest that dietary energy restriction can enhance neural plasticity and reduce the vulnerability of the brain to age-related dysfunction and disease. Dietary energy restriction may exert beneficial effects on the brain by engaging adaptive cellular stress response pathways resulting in the up-regulation of genes that encode proteins that promote neural plasticity and cell survival (e.g., neurotrophic factors, protein chaperones and redox enzymes). Two energy state-sensitive factors that are proving particularly important in regulating energy balance and improving/preserving cognitive function are brain-derived neurotrophic factor and glucagon-like peptide 1. Alternate day calorie restriction, novel insulin-sensitizing and neuroprotective agents, and drugs that activate adaptive stress response pathways, are examples of approaches for preserving cognitive function that show promise in preclinical studies.

No MeSH data available.


Related in: MedlinePlus