The nervous system governs our perceptions of reality, interpreting sound, light, and other physical stimuli through sensory organs. While these organs are efficient, they are inherently limited. Sensory organs allow us to construct a functional understanding of the world, but as we age, their gradual deterioration results in perceptual deficits, reduced cognitive function, and, in some cases, significant neurological challenges. While this decline is an expected part of aging, researchers have discovered that factors linked to the immune system can accelerate this process, contributing to a phenomenon referred to as “accelerated aging”.
So, what exactly is accelerated aging? Accelerated aging is defined as the set of mechanisms that cause biological aging – marked by the accumulation of cellular and DNA damage – to outpace chronological aging which refers to the number of years a person has lived. Various factors, including genetics, lifestyle, and environmental exposures, have been shown to accelerate this process. This raises an important question: how do the immune system and brain health influence accelerated aging?
Immunity and brain health are interconnected through a network of chemical signals and physical barriers that separate neural immune cells in the central nervous system (CNS) from systemic immune cells in the periphery. This separation is essential for maintaining homeostasis in the CNS, as systemic immune cells often exhibit pro-inflammatory traits that can damage delicate neural tissues within the nervous system. However, as the immune system ages, its balance with the CNS becomes increasingly fragile. Factors such as stress or inflammation can disrupt this equilibrium, which can ultimately impact biological aging.
Clinical studies investigating the role of stress on psychiatric health have demonstrated that mental health may be influenced by changes to the aging immune system. Several studies have conducted investigations to determine the relationship between immunity, brain health, and aging, given the limited understanding of molecular factors underlying many psychopathologies.
To examine this relationship, let’s explore specific mental health stressors or conditions that are influenced by such processes described above.
Social Stress
Researchers at the University of California, Los Angeles recently assessed 5,500 individuals to investigate social stressors (e.g., discrimination, trauma, etc.) and the effect they have on immune cell populations. Analysis of peripheral blood mononuclear cells, particularly T cells, revealed an increase in aged phenotypes incapable of adapting to new immune challenges. Regardless of controls for specific participant characteristics like education or smoking status, T cells were always shown to lack adaptability in individuals who faced high levels of social stress. Hence, exposure to social stressors can induce changes to T cells mimicking those created by aging and may ultimately impact brain health.
Depression
Immunosenescence refers to the gradual decline of immune function leading to chronic, low-grade inflammation, typically as a function of aging. Likewise, the aging CNS experiences breakdown of the blood-brain-barrier, which normally prevents systemic immune cells from accessing the brain. The combination of these effects has been studied, showing they may be related to the onset of depression. Morimoto and Alexopoulos (2012) studied immunity, aging, and geriatric depression, finding that aging disrupts communication between the peripheral and CNS-resident immune systems. This disruption promotes the production of pro-inflammatory phenotypes in the immune system in both the periphery and in the CNS. Quantification of these effects via cytokine analyses, neuroimaging, and electrophysiological analysis has corroborated these findings, showing that immunosenesence may be a direct causative agent in geriatric depression.
Other Psychopathologies
Clinicians diagnose psychopathologies using the Diagnostic and Statistical Manual of Mental Disorders (DSM). This manual provides clinicians with the range of symptoms expected in individuals with mental health concerns using specific behaviors, patterns of thought, and frequencies to ascertain whether an event is acute or chronic. While diagnostic criteria are primarily rooted in behavioral sciences, immunological research has found associations between such pathologies and immunity. For example, Chen et al. (2024) explored whether psychosis may be related to accelerated aging, specifically inflammaging—chronic, low-grade inflammation that appears with age. Chen suggests that much more research needs to be conducted, but developmental factors may attribute to a varied immune repertoire, increasing the risk of psychosis.
The immune system plays a central role in shaping brain health throughout the aging process, particularly from the perspective of mental health and stressors. As we age, the delicate balance between systemic and CNS immune responses becomes increasingly fragile, creating a pathway for inflammation and neurodegeneration to take hold. Understanding these interactions is critical for developing strategies to combat accelerated aging and improve quality of life in aging populations. Such research has not only expanded our understanding of the aging process, but also how such processes influence our mental health, possibly even expanding the potential for therapeutics within the field of psychiatry. By addressing both immune and mental health factors, we can take significant steps toward preserving cognitive and emotional resilience in later life.
References
Atrooz, Fatin, Hesong Liu, and Samina Salim. 2019. “Stress, Psychiatric Disorders, Molecular Targets, and More.” In Progress in Molecular Biology and Translational Science, 167:77–105. Elsevier. https://doi.org/10.1016/bs.pmbts.2019.06.006.
Bennett, F C, and A V Molofsky. 2019. “The Immune System and Psychiatric Disease: A Basic Science Perspective.” Clinical and Experimental Immunology 197 (3): 294–307. https://doi.org/10.1111/cei.13334.
Carson, Monica J., Jonathan M. Doose, Benoit Melchior, Christoph D. Schmid, and Corinne C. Ploix. 2006. “CNS Immune Privilege: Hiding in Plain Sight.” Immunological Reviews 213 (1): 48–65. https://doi.org/10.1111/j.1600-065X.2006.00441.x.
Chen, Song, Yunlong Tan, and Li Tian. 2024. “Immunophenotypes in Psychosis: Is It a Premature Inflamm-Aging Disorder?” Molecular Psychiatry 29 (9): 2834–48. https://doi.org/10.1038/s41380-024-02539-z.
Finger, Carson E., Ines Moreno-Gonzalez, Antonia Gutierrez, Jose Felix Moruno-Manchon, and Louise D. McCullough. 2022. “Age-Related Immune Alterations and Cerebrovascular Inflammation.” Molecular Psychiatry 27 (2): 803–18. https://doi.org/10.1038/s41380-021-01361-1.
Gadhvi, Mahesh, Marlyn J. Moore, and Muhammad Waseem. 2024. “Physiology, Sensory System.” In StatPearls. Treasure Island (FL): StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK547656/.
Godbout, Jonathan P., and Rodney W. Johnson. 2009. “Age and Neuroinflammation: A Lifetime of Psychoneuroimmune Consequences.” Immunology and Allergy Clinics of North America 29 (2): 321–37. https://doi.org/10.1016/j.iac.2009.02.007.
Klopack, Eric T., Eileen M. Crimmins, Steve W. Cole, Teresa E. Seeman, and Judith E. Carroll. 2022. “Social Stressors Associated with Age-Related T Lymphocyte Percentages in Older US Adults: Evidence from the US Health and Retirement Study.” Proceedings of the National Academy of Sciences 119 (25): e2202780119. https://doi.org/10.1073/pnas.2202780119.
Marzvanyan, Anna, and Ali F. Alhawaj. 2024. “Physiology, Sensory Receptors.” In StatPearls. Treasure Island (FL): StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK539861/.
Morimoto, Sarah Shizuko, and George S. Alexopoulos. 2011. “Immunity, Aging, and Geriatric Depression.” Psychiatric Clinics of North America 34 (2): 437–49. https://doi.org/10.1016/j.psc.2011.02.006.
Roberts, Katherine L., and Harriet A. Allen. 2016. “Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline.” Frontiers in Aging Neuroscience 8 (March). https://doi.org/10.3389/fnagi.2016.00039.
Wolkowitz, Owen M. 2018. “Accelerated Biological Aging in Serious Mental Disorders.” World Psychiatry 17 (2): 144–45. https://doi.org/10.1002/wps.20546.
Nicolas Wilson
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- Immune Function and Accelerated Brain Aging - January 20, 2025