Calorie restriction reduces psychological stress reactivity and its association with brain volume and microstructure in aged rhesus monkeys
Open accessAbstract
Background Heightened stress reactivity is associated with hippocampal atrophy, age-related cognitive deficits, and increased risk for Alzheimer's disease. This temperament predisposition may aggravate age-associated brain pathology or be reflective of it. This association may be mediated through repeated activation of the stress hormone axis over time. Dietary interventions, such as calorie restriction (CR), affect stress biology and may moderate the pathogenic relationship between stress reactivity and brain in limbic and prefrontal regions.Methods Rhesus monkeys (Macaca mulatta) aged 19-31 years consumed either a standard diet (N=18) or were maintained on 30% CR relative to baseline intake (N=26) for 13-19 years. Behavior was rated in both normative and aversive contexts. Urinary cortisol was collected. Animals underwent magnetic resonance imaging and diffusion tensor imaging (DTI) to acquire volumetric and tissue microstructure data respectively. Voxel-wise statistics regressed a global stress reactivity factor, cortisol, and their interaction on brain indices across and between dietary groups.Results CR significantly reduced stress reactivity during aversive contexts without affecting activity, orientation, or attention behavior. Stress reactivity was associated with less volume and tissue density in areas important for emotional regulation and the endocrine axis including prefrontal cortices, hippocampus, amygdala, and hypothalamus. CR reduced these relationships. A Cortisol by Stress Reactivity voxel-wise interaction indicated that only monkeys with high stress reactivity and high basal cortisol demonstrated lower brain volume and tissue density in prefrontal cortices, hippocampus, and amygdala.Conclusions High stress reactivity predicted lower volume and microstructural tissue density in regions involved in emotional processing and modulation. A CR diet reduced stress reactivity and regional associations with neural modalities. High levels of cortisol appear to mediate some of these relationships.
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Caloric restriction is associated with prolonged life, increased gray matter volume, improved motor function, and reduced chronic pathology and inflammatory markers in rodents, non-human primates, and humans.
“Caloric restriction (middle) is associated with prolonged life, increased gray matter volume, improved motor function, and reduced chronic pathology (eg, neoplasia) and inflammatory markers (complement proteins, antigen presentation markers, and pro-inflammatory cytokines) in rodents, non-human primates, and humans (Colman et al, 2009;Willette et al, 2012;Witte et al, 2009).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Willette et al, 2012
These effects were not observed in monkeys placed on 30% caloric restriction, suggesting that caloric restriction may attenuate the stress-induced behavioral and anatomical impairments associated with aging.
“These effects were not observed in monkeys placed on 30% caloric restriction, suggesting that caloric restriction may attenuate the stress-induced behavioral and anatomical impairments associated with aging (Willette et al, 2012).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Willette et al, 2012
Caloric restriction is associated with prolonged life in rodents, non-human primates, and humans.
“Caloric restriction (middle) is associated with prolonged life, increased gray matter volume, improved motor function, and reduced chronic pathology (eg, neoplasia) and inflammatory markers (complement proteins, antigen presentation markers, and pro-inflammatory cytokines) in rodents, non-human primates, and humans(Colman et al, 2009;Willette et al, 2012;Witte et al, 2009).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Willette et al, 2012
Caloric restriction is associated with improved motor function in rodents, non-human primates, and humans.
“Caloric restriction (middle) is associated with prolonged life, increased gray matter volume, improved motor function, and reduced chronic pathology (eg, neoplasia) and inflammatory markers (complement proteins, antigen presentation markers, and pro-inflammatory cytokines) in rodents, non-human primates, and humans(Colman et al, 2009;Willette et al, 2012;Witte et al, 2009).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Willette et al, 2012
Caloric restriction is associated with reduced inflammatory markers (complement proteins, antigen presentation markers, and pro-inflammatory cytokines) in rodents, non-human primates, and humans.
“Caloric restriction (middle) is associated with prolonged life, increased gray matter volume, improved motor function, and reduced chronic pathology (eg, neoplasia) and inflammatory markers (complement proteins, antigen presentation markers, and pro-inflammatory cytokines) in rodents, non-human primates, and humans(Colman et al, 2009;Willette et al, 2012;Witte et al, 2009).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Willette et al, 2012
Caloric restriction is associated with reduced chronic pathology (eg, neoplasia) in rodents, non-human primates, and humans.
“Caloric restriction (middle) is associated with prolonged life, increased gray matter volume, improved motor function, and reduced chronic pathology (eg, neoplasia) and inflammatory markers (complement proteins, antigen presentation markers, and pro-inflammatory cytokines) in rodents, non-human primates, and humans(Colman et al, 2009;Willette et al, 2012;Witte et al, 2009).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Willette et al, 2012
Caloric restriction is associated with increased gray matter volume in rodents, non-human primates, and humans.
“Caloric restriction (middle) is associated with prolonged life, increased gray matter volume, improved motor function, and reduced chronic pathology (eg, neoplasia) and inflammatory markers (complement proteins, antigen presentation markers, and pro-inflammatory cytokines) in rodents, non-human primates, and humans(Colman et al, 2009;Willette et al, 2012;Witte et al, 2009).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Willette et al, 2012
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References 75 · Cited by 41
- Authors
- Willette, A. A., Coe, C. L., Colman, R. J., Bendlin, B. B., Kastman, E. K., Field, A. S., Alexander, A. L., Allison, D. B., Weindruch, R. H., & Johnson, S. C.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Johnson, Sterling C.
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 37
- Issue
- 7
- Pages
- 903-916
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC3311744
- OpenAlex
- W2110441060
- Cited by
- 41
- References
- 75
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 8 · 2013: 4 · 2012: 2
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Research Resources
- National Institutes of Health (MH062015, GM007507, RR15459-01, AG000213, AG011915, RR000167, MH085051, RR020141-01, AG027343, AG20166, AI067518, HD057064)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- caloric restriction, cortisol, brain volume, white matter microstructure, hippocampus, amygdala, prefrontal cortex, hypothalamus, aging, rhesus monkeys, dietary intervention, emotion regulation, Alzheimer's disease risk
- MeSH terms
- Aging, Animals, Animal Feed, Behavior, Animal, Brain, Cell Count, Diet, Female, Hydrocortisone, Longitudinal Studies, Macaca mulatta, Male, Organ Size, Radiography, Stress, Psychological, Caloric Restriction
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