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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

Mechanisms by which excessive energy intake and low levels of energy expenditure adversely affect synaptic plasticity and cognitive function. Overeating adversely affects the brain because of the increased oxidative stress resulting from increased levels of glucose which may result in increased generation of superoxide anion radical in the mitochondria and a nonenzymatic process called glycation. Also contributing to increased molecular damage is the reduction in the activation of adaptive cellular stress response pathways (cellular complacency) which manifests as reduced production of neurotorphic factors, protein chaperones and antioxidant enzymes. Physical inactivity exacerbates the effects of excessive energy intake because exercise activates adaptive cellular stress response pathways that can protect neurons against dysfunction and degeneration. Overeating and a sedentary lifestyle therefore promote the progressive accumulation of damaged proteins, nucleic acids and membranes in brain cells resulting in impaired synaptic function and neurogenesis; neuronal degeneration and death may ensue. In these ways a ‘couch potato’ lifestyle may place the individual on a trajectory towards premature cognitive impairment and Alzheimer's disease.
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Figure 1: Mechanisms by which excessive energy intake and low levels of energy expenditure adversely affect synaptic plasticity and cognitive function. Overeating adversely affects the brain because of the increased oxidative stress resulting from increased levels of glucose which may result in increased generation of superoxide anion radical in the mitochondria and a nonenzymatic process called glycation. Also contributing to increased molecular damage is the reduction in the activation of adaptive cellular stress response pathways (cellular complacency) which manifests as reduced production of neurotorphic factors, protein chaperones and antioxidant enzymes. Physical inactivity exacerbates the effects of excessive energy intake because exercise activates adaptive cellular stress response pathways that can protect neurons against dysfunction and degeneration. Overeating and a sedentary lifestyle therefore promote the progressive accumulation of damaged proteins, nucleic acids and membranes in brain cells resulting in impaired synaptic function and neurogenesis; neuronal degeneration and death may ensue. In these ways a ‘couch potato’ lifestyle may place the individual on a trajectory towards premature cognitive impairment and Alzheimer's disease.

Mentions: Additional mechanisms by which high fat/energy diets impair cognitive function are beginning to be elucidated and involve adverse effects on synaptic plasticity and neurogenesis (Figure 1). High energy/fat diets may impair hippocampal plasticity by reducing the expression of brain-derived neurotrophic factor (BDNF). BDNF is a protein produced by neurons in an activity-dependent manner; two transcription factors that are known to induce the expression of the BDNF gene are cyclic AMP response element binding protein (CREB) and nuclear factor κ-B (NF-κB) (Lipsky and Marini, 2007). BDNF activates a high-affinity receptor tyrosine kinase called trkB, which is located in the plasma membrane where it present in particularly high amounts in dendrites and presynaptic terminals. Activated trkB engages a signaling pathway involving PI3 kinase, Akt kinase and FOXO transcription factors; this pathway induces the expression of genes that enhance synaptic plasticity (glutamate receptor subunits and growth-associated protein 43, for example) and cell survival (the antioxidant enzyme superoxide dismutase 2, and the anti-apoptotic protein Bcl-2, for example) (Koponen et al., 2004; Mattson et al., 2004; Pang and Lu, 2004; Bramham and Messaoudi, 2005). In addition to enhancing synaptic plasticity and neuron survival, BDNF has been shown to stimulate neurogenesis (the differentiation of neurons from neural stem cells) (Cheng et al., 2003; Schmidt and Duman, 2007) which may contribute to the beneficial effects of BDNF on cognitive function.


The impact of dietary energy intake on cognitive aging.

Mattson MP - Front Aging Neurosci (2010)

Mechanisms by which excessive energy intake and low levels of energy expenditure adversely affect synaptic plasticity and cognitive function. Overeating adversely affects the brain because of the increased oxidative stress resulting from increased levels of glucose which may result in increased generation of superoxide anion radical in the mitochondria and a nonenzymatic process called glycation. Also contributing to increased molecular damage is the reduction in the activation of adaptive cellular stress response pathways (cellular complacency) which manifests as reduced production of neurotorphic factors, protein chaperones and antioxidant enzymes. Physical inactivity exacerbates the effects of excessive energy intake because exercise activates adaptive cellular stress response pathways that can protect neurons against dysfunction and degeneration. Overeating and a sedentary lifestyle therefore promote the progressive accumulation of damaged proteins, nucleic acids and membranes in brain cells resulting in impaired synaptic function and neurogenesis; neuronal degeneration and death may ensue. In these ways a ‘couch potato’ lifestyle may place the individual on a trajectory towards premature cognitive impairment and Alzheimer's disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Mechanisms by which excessive energy intake and low levels of energy expenditure adversely affect synaptic plasticity and cognitive function. Overeating adversely affects the brain because of the increased oxidative stress resulting from increased levels of glucose which may result in increased generation of superoxide anion radical in the mitochondria and a nonenzymatic process called glycation. Also contributing to increased molecular damage is the reduction in the activation of adaptive cellular stress response pathways (cellular complacency) which manifests as reduced production of neurotorphic factors, protein chaperones and antioxidant enzymes. Physical inactivity exacerbates the effects of excessive energy intake because exercise activates adaptive cellular stress response pathways that can protect neurons against dysfunction and degeneration. Overeating and a sedentary lifestyle therefore promote the progressive accumulation of damaged proteins, nucleic acids and membranes in brain cells resulting in impaired synaptic function and neurogenesis; neuronal degeneration and death may ensue. In these ways a ‘couch potato’ lifestyle may place the individual on a trajectory towards premature cognitive impairment and Alzheimer's disease.
Mentions: Additional mechanisms by which high fat/energy diets impair cognitive function are beginning to be elucidated and involve adverse effects on synaptic plasticity and neurogenesis (Figure 1). High energy/fat diets may impair hippocampal plasticity by reducing the expression of brain-derived neurotrophic factor (BDNF). BDNF is a protein produced by neurons in an activity-dependent manner; two transcription factors that are known to induce the expression of the BDNF gene are cyclic AMP response element binding protein (CREB) and nuclear factor κ-B (NF-κB) (Lipsky and Marini, 2007). BDNF activates a high-affinity receptor tyrosine kinase called trkB, which is located in the plasma membrane where it present in particularly high amounts in dendrites and presynaptic terminals. Activated trkB engages a signaling pathway involving PI3 kinase, Akt kinase and FOXO transcription factors; this pathway induces the expression of genes that enhance synaptic plasticity (glutamate receptor subunits and growth-associated protein 43, for example) and cell survival (the antioxidant enzyme superoxide dismutase 2, and the anti-apoptotic protein Bcl-2, for example) (Koponen et al., 2004; Mattson et al., 2004; Pang and Lu, 2004; Bramham and Messaoudi, 2005). In addition to enhancing synaptic plasticity and neuron survival, BDNF has been shown to stimulate neurogenesis (the differentiation of neurons from neural stem cells) (Cheng et al., 2003; Schmidt and Duman, 2007) which may contribute to the beneficial effects of BDNF on cognitive function.

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