Perceived Stress is Associated with Accelerated Monocyte/Macrophage Aging Trajectories in Clinically Normal Adults
Open accessAbstract
Objectives Chronic stress is associated with poorer age-related cognition, but the mechanisms of this relationship are not well understood. Aging increases expression of activated macrophages, leading to exacerbated immune responses to stressors. We examined the impact of stress and aging on macrophage-related inflammation and cognition in clinically normal adults.Methods Three hundred eighty clinically normal adults were followed longitudinally (age M = 73 years; visit range: 1-8; M = 2.5 visits). Participants completed the Perceived Stress Scale, a neuropsychological battery, and blood draws. Plasma was analyzed for cytokines related to macrophage function (interleukin 6, tumor necrosis factor alpha, macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta). Linear mixed-effects examined the effects of age, baseline stress, and their interaction predicting macrophage cytokines, adjusting for sex, education, and depressive symptoms. Latent growth curve models assessed the mediating role of macrophage cytokines in the relationship between age and cognition in high or low stress.Results Baseline perceived stress interacted with age to predict macrophage cytokines longitudinally. Specifically, high-stress adults demonstrated accelerated age-related elevations in macrophage cytokines across time. Macrophage cytokines negatively tracked with executive functioning longitudinally. Macrophage cytokines mediated 19% of the relationship between age and executive function in high-stress, but not low-stress, adults.Conclusions Our data provide evidence of accelerated immune aging among individuals with high stress. Elevated macrophage cytokine trajectories mediated the effect of age on executive function only in individuals with high stress, suggesting these constructs may be more tightly linked in elevated stress contexts. Stress interventions are warranted to optimize immune aging, with possible downstream cognitive benefits among even clinically normal adults.
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Improving mental health and alleviating psychological stress have a positive effect on aging.
“These findings suggest that improving mental health and alleviating psychological stress have a positive effect on aging.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [336]
The Conclusions associate higher perceived stress with accelerated immune-aging trajectories in clinically normal adults and recommend stress-reduction interventions as a potential way to improve aging outcomes. They do not test whether alleviating stress improves aging, and the reported effects were independent of mood; the broader claim about improving mental health is not established. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA longitudinal study found that the elevation of inflammatory markers increased in elderly people with high self-reported stress levels during follow-up.
“In addition. A longitudinal study found that the elevation of inflammatory markers increased in elderly people with high self-reported stress levels during follow-up.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [336]
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- Authors
- Casaletto, K. B., Staffaroni, A. M., Elahi, F., Fox, E., Crittenden, P. A., You, M., Neuhaus, J., Glymour, M., Bettcher, B. M., Yaffe, K., & Kramer, J. H.
- Affiliations
- University of California, San Francisco (US)
- University of Colorado Anschutz (US)
- Corresponding author
- Casaletto, Kaitlin B.
- ORCID
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 26
- Issue
- 9
- Pages
- 952-963
- ISSN
- 1064-7481 (ISSN-L)
- PMC
- PMC6108924
- OpenAlex
- W2807934966
- Cited by
- 47
- References
- 46
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 1
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH-NIA (NIA 1R01AG032289, R01AG048234, NIA K23AG058752, L30 AG057123)
- University of California, San Francisco (P50 AG023501)
- Larry L. Hillblom Network (2014-A-004-NET)
- Fellowship grants (2017-A-004-FEL)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- perceived stress, immunosenescence, macrophage-derived cytokines, interleukin-6, TNF-α, MIP-1, executive function, age-related cognitive decline, chronic stress, older adults
- MeSH terms
- Aged, Aged, 80 and over, Aging, Female, Humans, Inflammation, Longitudinal Studies, Macrophages, Male, Middle Aged, Stress, Psychological, Tumor Necrosis Factor-alpha, Interleukin-6, Chemokine CCL3, Chemokine CCL4, Cognitive Dysfunction
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