The Aging Human Brain – Country Highlights

The prevalence of neurodegenerative disorders has increased over the past several decades for several reasons. Age is a major risk factor; However, increased rates of these disorders are also associated with cognitive impairment in the absence of overt neurodegeneration.

a new one Frontiers in Human Neuroscience The review paper describes changes at the molecular and cellular levels, as well as within neuronal networks, underlying brain aging in otherwise healthy older adults.

study: Horizons in Human Aging Neuroscience: From Normal Neural Aging to Mental (Fr) Agility. Image credit: Naeblys / Shutterstock.com

introduction

Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and stroke are more common among people over the age of 55. Aging is a primary risk factor for declines in mental agility and vigor, as well as for age-related cognitive decline in apparently normal-aged individuals. mind

Researchers from the University of Amsterdam aimed to distinguish normal aging from neural aging using neurobiological and neuropsychological markers. In normal aging, older adults continue to enjoy mental health, although they have suffered some impairment in physical and cognitive function. In contrast, with neural aging, functional abilities and competencies that are essential for mental health are not developed or successfully maintained.

The World Health Organization (WHO) has referred to the current decade as the ‘Decade of Healthy Aging’, thus indicating the great value placed on protecting the physical and mental health of the elderly. This is even more important considering that more than 25% of the Western population today is over 65 years of age.

Why does the human brain age?

A normal body has a wide range of cellular and molecular mechanisms responsible for short-term survival, including reproductive selection for longevity. As more injuries accumulate, these mechanisms become progressively dysfunctional, leading to functional decline.

The most specialized cells in the body are neurons. However, these cells are associated with an increased risk of degeneration with age which is in place to limit the energetic costs of repair and maintenance of neurons beyond a certain point of injury. For example, accumulated DNA damage can cause errors in the transcription and translation of proteins to allow damaged cells to die when necessary.

The brain is an important link between external and internal challenges to the state of the organism. Furthermore, the brain acts as a ‘master coordinator of actions’ that can achieve favorable conditions while avoiding unfavorable ones.

The brain is also responsible for memory, decision-making, perception-action selection, balancing between planning and exploitation and exploration, maintaining rule-based behavior through flexibility, as well as speed and accuracy of responses. Taken together, these two brain functions demonstrate the relationship between errors in brain function and structure, and mental dysfunction.

Markers of neural aging

Many factors contribute to neural aging.

Mitochondria, for example, are primarily responsible for energy homeostasis at the cellular level. Thus, dysfunction of this organ affects a wide range of metabolic processes involving glucose, calcium ions, key enzymes, and molecules, as well as antioxidant mechanisms to reduce oxidative stress, DNA damage, and inactivation of reactive oxygen species. ).

Abnormal metabolism, as well as inactive proteins and mitochondria, can accumulate within neurons. It occurs as a result of an imbalance between oxidative stress and antioxidant defenses, as well as a waste disposal system due to outdated lysosomes and proteasomes.

Microglia often weaken with age and exhibit slower brain injury responses. Inflammaging, which is a chronic condition of mild inflammation with aging neurons, is another aspect of neural aging.

These different aspects of aging make neurons more susceptible to functional loss while simultaneously weakening neuronal immunity. The resulting cognitive and functional changes vary among individuals depending on the specific challenges posed by their environment and the capacity of their immune systems.

Neural versus network changes

Neural aging also involves senescence of neurons, exhaustion 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 declining levels with corresponding reductions in neuroplasticity. Long-term potentiation (LTP) is decreased, while long-term depression (LTD) is increased neuronal transmission.

Within the hippocampus, such loss of plasticity, especially with stress, accelerates age-related cognitive decline. Meanwhile, regions such as the default mode network (DMN) that are suppressed in specific tasks may be spared from such inactivation in the aging brain.

In addition, the prefrontal cortex is more active during tasks, a phenomenon known as compensatory recruitment, that are particularly vulnerable to damage.

This pattern is linked to behavioral changes, such as exploitative behaviors to exploratory behaviors with increasing age. Overall, neural dysfunction is associated with impaired neuroplasticity, providing a link between individual neurons and neuronal network failures in aging.

Can neural aging be prevented?

Scientists in the current study also discovered promising anti-neural aging effects of several interventions aimed at normalizing metabolic parameters in the elderly. These include calorie restriction and exercise and can also address other risk factors such as reducing stress and improving sleep, as well as increasing the quality of the gut microbiome.

A diet rich in antioxidants and beneficial fats may protect against accumulated damage, while a diet high in sugar and saturated fat may exacerbate such damage. Intermittent fasting appears to reduce such damage in experimental animals by increasing the biogenesis of neuronal mitochondria and reducing the effects of oxidative stress on these organelles. A diet that promotes a healthy gut microbiome may also help protect neuronal health.

Caloric restriction and exercise act through different pathways to enhance neuronal recovery during rest and sleep, as well as neuroplasticity and stress resistance. Previous research in humans has indicated that exercise improves hippocampal structure and function while also reducing cognitive impairment.

Sleep acts in several ways to protect the brain from neurodegeneration, particularly in the hippocampus. To this end, sleep promotes neuronal repair and immune responses while simultaneously removing waste products such as amyloid plaques.

Stress, loneliness, and inflammation are closely linked and can be alleviated by appropriate measures to reduce stress.

Volunteering activities increase social connectedness, as well as cognitive flexibility, and activation of the prefrontal cortex.”

Pharmacological interventions have also been described in experimental animals, with some agents such as ergothioneine being approved as supplements. Perhaps these drugs can slow the rate of cognitive decline; However, more research is needed.

Meanwhile, learning new skills increases the size of the hippocampus. However, its effect on general cognition is controversial and should be further studied.

conclusion

Many biological and molecular changes are associated with neuronal aging. These include metabolic shifts, oxidative stress, DNA damage, inflammation, and impaired regulation of calcium. These processes form an interconnected network that reduces brain plasticity, with a corresponding reduction in cognitive function.

Mitochondrial dysfunction, once exceeding a certain threshold, can begin to show a decline, and then drag on its “decline” along with other features of neural aging, thus triggering a cascade that at some point also leads to the decline of supported cognitive functions. may be by neuronal ensembles and networks.”

Researchers have suggested that the mitochondrial cascade model of Alzheimer’s disease may also apply to normal aging.

The underlying mechanisms by which neural aging occurs cannot be explained by a single neurobiological factor. Rather, these tightly coupled factors appear to influence each other.

We hypothesize that declines in one feature of neural aging may lead to declines in other, otherwise stable subsystems, thereby triggering a cascade that may eventually lead to declines in cognitive functions and mental health..”

Further research is needed to understand the overall network of age-related changes at all levels. Future studies should also be directed at providing support for interventions that can prevent these changes from occurring, thereby ameliorating cognitive decline while increasing the mental frailty associated with aging.