Does the Brain Slow Down Our Aging Process?

Key points

Inflammation plays a critical role in aging and age-related diseases.

The immune system has mechanisms for resolving inflammation that are impaired in elderly individuals.

The brain is capable of sending an antiinflammatory signal to inflamed tissues and disrupted with aging.

It has been observed that individuals with mental disorders such as anxiety , depression , and schizophrenia experience accelerated aging. The brain controls numerous vital processes, including respiration, heart rate, blood pressure, hormone regulation, and sensory perception . However, the control of aging is an unexpected function of the brain.

Aging is the gradual decline in the functions and structure of tissues and organs. The wear-and-tear theory of aging assumes that cells, like machines, wear out. Unlike machines, cells are capable of repairing themselves; however, they lose this ability with aging. Damage to biomolecules by free radicals is another mechanism that causes aging in organisms. Mitochondrial dysfunction contributes to the production of these radicals as part of the aging process. Unrepaired and accumulated biomolecules, such as nucleic acids and proteins, gradually lead to cellular dysfunction. Genetic variations or epigenetic mechanisms that cause alterations in gene expression patterns are other proposed mechanisms of aging. One theory of aging suggests that hormonal system changes contribute to the onset of aging.

A recent study revealed that the hypothalamus, responsible for regulating basic needs and behaviors such as the hormonal system, metabolism, hunger, sleep, fear , and violence, also influences the aging process. In this study, researchers investigated a specific group of stem cells in the hypothalamus during the aging process of mice. Mice typically have a lifespan of about two years, but the researchers discovered that these cells start to diminish at around 11 months of age and are entirely depleted by 22 months. The rate at which these stem cells die is closely related to aging changes in animals, such as a decline in learning, memory , social interaction, muscle endurance, and athletic performance.

Since correlation does not imply causation, the researchers tried to remove the stem cells using a specially engineered virus designed to destroy them. In 15-month-old mice that received this medication combination, 70% of hypothalamic stem cells were destroyed. These mice exhibited premature signs of aging and consequently died earlier. The team also implanted hypothalamic stem cells from young mice into older animals. As a result, the animals displayed increased sociability, improved cognitive abilities, and lived approximately 200 days longer than their counterparts. The researchers proposed a mechanism in which hypothalamic stem cells secrete membrane-bound extracellular vesicles consisting of small regulatory RNA (microRNAs) into the cerebrospinal fluid, and these vesicles decline with aging [1]. These results revealed an important finding that a part of the brain is involved in the aging process.

Inflammation also significantly impacts the etiology of aging. The term “inflammageing” was coined to describe the elevated levels of proinflammatory markers in the blood and tissues of elderly subjects. These factors often originate from damaged or infected tissues and or a cellular state known as senescence , or aging cells. Inflammation is normally intricately controlled by the immune system to start at the right time and to stop after the removal of damage or infection. Disruption of resolution of inflammation as the final step in the normal inflammatory process causes sustained or chronic inflammation [2].

In addition to the immune system, the brain plays a key role in regulating the immune system, inflammation, and stress responses through the vagus nerve , a major component of the parasympathetic nervous system , PNS. Studies have shown that stimulating the vagus nerve can reduce inflammation and improve immune function, potentially benefiting aging-related conditions such as Alzheimer’s disease, cardiovascular disease, and diabetes. Interestingly, some studies have shown a link between aging and a decrease in parasympathetic activity [3].

On the opposite side, the sympathetic nervous system (SNS) has a dual effect on immune function. The acute activation of SNS with brief stressors stimulates the immune system’s efficacy as part of the fight-or-flight response of this system. Prolonged and chronic stressors, however, suppress the immune system and the recruitment of immune cells to inflammatory sites. Several lines of evidence have revealed that SNS activation increases during aging, and this implicates age-related increases in blood pressure and cardiovascular diseases [4]. However, the association between SNS and immune response is complex and is related to the context.

Studies have shown that the higher part of the brain influences the regulation of the autonomic nervous system, immune system, and inflammation, and subsequently contributes to inflammageing. Research has shown that the prefrontal cortex, which regulates thoughts, emotions, and responses to stress, can modulate the PNS. For instance, mindfulness , meditation , and deep breathing techniques can enhance the anti-inflammatory action of the PNS and the vagus nerve. Furthermore, the neocortex, which is responsible for perceptions, cognition, and memory, also affects the immune system and inflammation through its connections with the hypothalamus and other brain regions involved in regulating the autonomic nervous system. Therefore, it is reasonable to assume that our emotions, thoughts, reactions, and beliefs indirectly impact our immune response and consequently contribute to conditions associated with inflammation, such as aging. It is not far from the truth that individuals who maintain a positive mindset tend to enjoy a longer period of good health and age more gracefully.

References

1. Zhang, Y., Kim, M. S., Jia, B., Yan, J., Zuniga-Hertz, J. P., Han, C., & Cai, D. (2017). Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature, 548(7665), 52-57. doi:10.1038/nature23282

2. Xia, S., Zhang, X., Zheng, S., Khanabdali, R., Kalionis, B., Wu, J., . . . Tai, X. (2016). An Update on Inflamm-Aging: Mechanisms, Prevention, and Treatment. J Immunol Res, 2016, 8426874. doi:10.1155/2016/8426874

3. Jiang, Y., Yabluchanskiy, A., Deng, J., Amil, F. A., Po, S. S., & Dasari, T. W. (2022). The role of age-associated autonomic dysfunction in inflammation and endothelial dysfunction. Geroscience, 44(6), 2655-2670. doi:10.1007/s11357-022-00616-1

4. Balasubramanian, P., Hall, D., & Subramanian, M. (2019). Sympathetic nervous system as a target for aging and obesity-related cardiovascular diseases. Geroscience, 41(1), 13-24. doi:10.1007/s11357-018-0048-5

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