Energy intake and exercise as determinants of brain health and vulnerability to injury and disease
Open accessAbstract
Evolution favored individuals with superior cognitive and physical abilities under conditions of limited food sources, and brain function can therefore be optimized by intermittent dietary energy restriction (ER) and exercise. Such energetic challenges engage adaptive cellular stress-response signaling pathways in neurons involving neurotrophic factors, protein chaperones, DNA-repair proteins, autophagy, and mitochondrial biogenesis. By suppressing adaptive cellular stress responses, overeating and a sedentary lifestyle may increase the risk of Alzheimer's and Parkinson's diseases, stroke, and depression. Intense concerted efforts of governments, families, schools, and physicians will be required to successfully implement brain-healthy lifestyles that incorporate ER and exercise.
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Exercise influences neurogenesis in the dentate gyrus and increases synapse plasticity.
“In particular, exercise has been shown to influence neurogenesis in the dentate gyrus (67, 68) and to increase synapse plasticity (67, 68).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [68]
Physical exercise has positive health effects on cognitive function and brain health.
“Evidence is accumulating that physical exercise has positive health effects on cognitive function and brain health (67, 68).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [68]
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Effect of caloric restriction on base-excision repair (BER) in the aging rat brain
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Voluntary exercise may engage proteasome function to benefit the brain after trauma
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Body Mass Index across midlife and cognitive change in late life : delayed and cumulative effects
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Increased activity of surviving locus ceruleus neurons in Alzheimer's disease
Moser (1999) · Pure Amsterdam UMC · doi:10.1002/1531-8249(199901)45:1
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Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway
Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., Lin, J. D., Greenberg, M. E., & Spiegelman, B. M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.008 · Cited by 1,440 · see citing works
Fasting: molecular mechanisms and clinical applications
Longo, V. D., & Mattson, M. P. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.008 · Cited by 1,425 · see citing works
Self-citationHallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States
Mattson, M. P., & Arumugam, T. V. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.05.011 · Cited by 1,242 · see citing works
Self-citationMuscle–Organ Crosstalk: The Emerging Roles of Myokines
Severinsen, M. C. K., & Pedersen, B. K. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa016 · Cited by 1,226 · see citing works
“In particular, exercise has been shown to influence neurogenesis in the dentate gyrus (67, 68) and to increase synapse plasticity (67, 68).”
BackgroundImpact of intermittent fasting on health and disease processes
Mattson, M. P., Longo, V. D., & Harvie, M. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.10.005 · Cited by 1,187 · see citing works
Self-citationExercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models
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Mitophagy and Alzheimer’s Disease: Cellular and Molecular Mechanisms
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Physical activity and muscle-brain crosstalk
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Brain metabolism in health, aging, and neurodegeneration
Camandola, S., & Mattson, M. P. (2017) · The EMBO Journal · doi:10.15252/embj.201695810 · Cited by 752 · see citing works
Self-citationIntermittent metabolic switching, neuroplasticity and brain health
Mattson, M. P., Moehl, K., Ghena, N., Schmaedick, M., & Cheng, A. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.156 · Cited by 624 · see citing works
Self-citationBDNF mediates adaptive brain and body responses to energetic challenges
Marosi, K., & Mattson, M. P. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.10.006 · Cited by 568 · see citing works
Self-citationCheng, A., Yang, Y., Zhou, Y., Maharana, C., Lu, D., Peng, W., Liu, Y., Wan, R., Marosi, K., Misiak, M., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.10.013 · Cited by 371 · see citing works
Self-citationKann, O., Papageorgiou, I. E., & Draguhn, A. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.104 · Cited by 295 · see citing works
Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies
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Nutrition for the ageing brain: Towards evidence for an optimal diet
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Marosi, K., Kim, S. W., Moehl, K., Scheibye‐Knudsen, M., Cheng, A., Cutler, R., Camandola, S., & Mattson, M. P. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13868 · Cited by 242 · see citing works
Self-citationIntermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.
Vasconcelos, A. R., Yshii, L. M., Viel, T. A., Buck, H. S., Mattson, M. P., Scavone, C., & Kawamoto, E. M. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-85 · Cited by 210 · see citing works
Fang, E. F., Waltz, T. B., Kassahun, H., Lu, Q., Kerr, J. S., Morevati, M., Fivenson, E. M., Wollman, B. N., Marosi, K., Wilson, M. A., et al. (2017) · Scientific Reports · doi:10.1038/srep46208 · Cited by 187 · see citing works
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Self-citationExercise and regulation of adipokine and myokine production
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Myokines mediate the cross talk between skeletal muscle and other organs
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APOE Stabilization by Exercise Prevents Aging Neurovascular Dysfunction and Complement Induction
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Caloric restriction: Beneficial effects on brain aging and Alzheimer’s disease
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Protective actions of exercise-related FNDC5/irisin in memory and Alzheimer's disease
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Neuroprotective effects of dietary restriction: Evidence and mechanisms
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Does PGC1α/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders?
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“…including exercise and intermittent fasting, which were previously reported to enhance autophagy and stimulate CREB signaling (Altarejos and Montminy 2011; Mattson 2012; Jamart et al. 2013; Yang et al. 2014), even though DNP has the specific effect to enhance energy (a) (b) (c) (d) (e) Fig.”
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Intergenerational Metabolic Syndrome and Neuronal Network Hyperexcitability in Autism
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Self-citationHormones, Metabolism and the Benefits of Exercise
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- Authors
- Mattson, M. P.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Mattson, Mark P.
- ORCID
- Mattson, Mark P.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 16
- Issue
- 6
- Pages
- 706-722
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3518570
- OpenAlex
- W2015620326
- Cited by
- 434
- References
- 196
- Citations by year
- 2026: 23 · 2025: 26 · 2024: 26 · 2023: 31 · 2022: 35 · 2021: 39 · 2020: 33 · 2019: 34 · 2018: 23 · 2017: 34 · 2016: 38 · 2015: 41 · 2014: 36 · 2013: 14 · 2012: 1
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (ZIAAG000313, ZIAAG000314, ZIAAG000330, ZIAAG000331, ZIAAG000312, ZIAAG000324, ZIAAG000315, ZIAAG000317)
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- caloric restriction, physical activity, brain health, neurodegeneration, Alzheimer's disease, Parkinson's disease, stroke, depression, cellular stress response, neurotrophic factors, autophagy, mitochondrial biogenesis, molecular chaperones, DNA repair, overeating, sedentary lifestyle
- MeSH terms
- Brain, Energy Intake, Humans, Neurons, Exercise, Neurodegenerative Diseases, Caloric Restriction
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