The aging brain
The prevalence of neurodegenerative disorders has increased in recent decades for several reasons. Age is a major risk factor; however, the increased rate of these disorders is also related to cognitive impairment in the absence of overt neurodegeneration. Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and stroke with its sequelae are more common among people over the age of 55. Aging is a primary risk factor for decreased mental agility and stamina, as well as age-related cognitive decline in individuals with apparently normal brains.
The current decade has been called “the decade of healthy aging” by the WHO, thus indicating the great value placed on protecting the physical and mental well-being of the elderly. This remains even more important considering that people over the age of 65 now represent over 25% of the Western population. And with the simultaneous prevalence of medical conditions whose complications also have repercussions on the nervous system, such as diabetes, the problem will very soon become yet another global emergency like obesity, diabetes and cardiovascular disease.
Why the human brain ages
The normal body is made up of a wide range of cellular and molecular mechanisms that are responsible for ensuring short-term survival, including the choice of reproduction over longevity. As more lesions accumulate, these mechanisms become progressively dysregulated, thus allowing for functional degeneration. The most specialized cells in the body are neurons. However, these cells are associated with an increased risk of degeneration with age that is in place to limit the energy costs of repairing and maintaining neurons beyond a certain point of injury. For example, accumulated DNA damage can cause errors in transcription and translation of proteins to allow damaged cells to die when needed. Remember that once dead neurons cannot regenerate.
The only hope is that there is a biological stimulation that will keep the activity of the brain niches that contain stem cells constant. These can regenerate neurons and go to “plug” areas that are particularly “damaged” by cell loss, even if to a limited extent. The brain is a vital link between external and internal challenges to the state of the organism. In addition, the brain acts as a “main coordinator of actions, responsible for memory, decision making, perception-action selection, planning and maintaining a balance between exploitation and exploration, maintaining rules-based behavior through flexibility. , the speed and accuracy of responses.
Taken together, these two brain functions demonstrate the association that exists between errors in brain function and structure and mental dysfunction. The accumulation of cellular errors (mostly induced by oxidative stress), but also by the chronic use of certain categories of drugs, exposure to voluptuous toxins (e.g. cigarette smoke) or environmental or derived from contamination in the diet it is the basis of the whole process of deterioration of the body and also of the brain. That it then manifests itself as inflammatory, cellular, immune alterations and so on, is only collateral. It is the biological damage done over the years that, accumulating, then manifests itself in the years to come: And the more numerous the list of damages, the more numerous the list of sequelae becomes.
Neural aging markers
Several factors contribute to neural aging. Mitochondria, for example, are primarily responsible for energy homeostasis at the cellular level. Therefore, the dysfunction of this organelle affects a wide range of metabolic processes involving glucose, calcium ions, key enzymes and molecules, as well as antioxidant mechanisms to mitigate the effects of oxidative stress, DNA damage and the deactivation of reactive species of the organelle. oxygen (ROS). Abnormal metabolites, as well as dysfunctional proteins and mitochondria, can accumulate within neurons. This occurs due to an imbalance between oxidative stress and antioxidant defenses, as well as a compromised waste disposal system due to aging lysosomes and proteasomes.
Microglia often exhibit altered and slower brain injury responses with age. Sub-clinical inflammation, which is a chronic state of mild inflammation with aging neurons, is another aspect of neural aging. These various aspects of aging cause neurons to become more susceptible to functional deterioration while neuronal defenses simultaneously weaken. The resulting cognitive and functional changes vary between individuals depending on the specific challenges posed by their environments and the capacity of their defense systems. They range from simple memory problems, to mood alterations up to conditions of real psychiatric illness, such as depression and behavioral alterations.
Changes in the neural network
Neural aging also involves the senescence of neurons, depletion of stem cells, as well as changes in neuronal characteristics, including their integrity, activity, plasticity and communication. Neuronal networks also show abnormal activity and altered connections with age. Many neurotransmitters show falling levels with corresponding decreases in neuroplasticity. Within the hippocampus, this loss of plasticity, especially with stress, accelerates age-related cognitive decline. Meanwhile, areas such as the default mode network (DMN) that are suppressed during specific tasks escape such deactivation in the aging brain.
At the same time, the prefrontal cortex becomes more active during homework, a phenomenon known as compensatory recruitment which is particularly vulnerable to damage. This model has been linked to behavioral changes, such as increased exploitation behaviors, versus exploratory behaviors with advancing age. And this is probably, at least in part, the underlying reason for the behavior that relatives observe in their loved ones who undergo certain forms of senile dementia, with the appearance of selfish behavior and obstinacy or opposition to attempts at personal care.
Can neural aging be combated?
Scientists investigated the promising aging effects of several interventions aimed at normalizing metabolic parameters in the elderly. These include calorie restriction and exercise, and may also involve addressing other risk factors such as reducing stress and improving sleep, as well as improving the quality of the gut microbiome. A diet rich in antioxidants and beneficial fats (of the omega-3 type) can protect against accumulated damage, while diets rich in simple sugars and saturated fats can aggravate such damage. Intermittent fasting appears to improve this damage in experimental animals by improving the biogenesis of neuronal mitochondria and reducing the impact of oxidative stress on these organelles. Among other things, over the centuries various cultures have supported the effectiveness of periodic fasting as a factor in maintaining health.
A diet that promotes a healthy gut microbiota could also help preserve neuronal health. The balance of the microbiota as a factor of human health is the exemplification of the “dogmatic” declaration of oriental medicine “human health passes through the intestine”. For more information, this site contains many articles on the topic of microbiota. Just search by keyword. Calorie restriction and exercise work through different pathways to improve neuronal recovery during rest and sleep, as well as increase neuroplasticity and resistance to stress. Previous human research has indicated that exercise improves hippocampal structure and function while also reducing cognitive impairment. Sleep works in different ways (immunological, metabolic, etc.) to protect the brain from the risk of neurodegeneration, especially in the hippocampus.
To this end, sleep improves neuronal repair and immune responses by simultaneously eliminating waste products such as amyloid plaques. Stress, loneliness and depression are closely linked by underlying inflammatory phenomena and can be mitigated by appropriate measures to reduce stress. Volunteering activities promote social connection, cognitive flexibility and greater activation of the prefrontal cortex. Pharmacological interventions have also been described in experimental animals, with some agents such as acetylcysteine and ergothioneine being approved as supplements. Perhaps their periodic introduction can reduce the rate of cognitive decline; however, more research is needed. Meanwhile, learning new skills is known to increase the size of the hippocampus, a central region for memory and home to stem cell niches.
There have been many recommendations that sedentary lifestyle, inertia, disinterest in reading or various forms of learning are all factors that “atrophy” the mind. In short, the brain must be kept in training as it does with the muscles when you go to the gym. For the muscles there are weights, for the brain you need reading, curiosity, music and serenity.
As we have seen, there are many biological and molecular changes associated with neuronal aging. These include metabolic changes, oxidative stress, DNA damage, inflammation, and impaired regulation of ion currents. These processes form an interconnected network that causes brain plasticity to decline, with a corresponding decrease in cognitive function. Researchers suggest that the mitochondrial cascade model of Alzheimer’s disease may also apply to normal aging.
The mechanism behind which neural aging occurs cannot be explained by a single neurobiological factor. Not to mention, that in the last decade, the microbiota factor with its influences on physiological and neurochemical metabolism have been unequivocally demonstrated. Instead, all of these densely connected factors seem to influence each other. Future studies should also be directed at providing support for interventions that can prevent these changes from occurring, thereby reducing the risk of cognitive decline and preventing aging-related mental frailty.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Ridderinkhof KR, Krugers HJ. Front Hum Neurosci 2022; 16:815759.
Willis CM, Nicaise AM, Krzac G et al. Exp Neurol. 2022; 355:114124.
Walker KA, Basisty N et al. J Clin Invest. 2022 Jul; 132(14):e158448.
Brinkhof LP, Huth KBS et al. Front Psychol. 2021 Nov 15; 12:752564.
Dott. Gianfrancesco Cormaci
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