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Aging and cognitive resilience: Molecular mechanisms as new potential therapeutic targets
Keywords
Introduction
In recent years, aging rates have been increasing due to greater longevity combined with falling birth rates around the world.(p1) The increase in human life expectancy over the last two centuries represents a remarkable achievement of modern civilization. However, it has also become a worldwide concern; in particular, there is a need to discover the mechanisms underlying cognitive aging given the increase in dementia cases in Portugal and worldwide.(p2)
Aging, a complex, natural, and gradual process experienced by all living beings, is characterized by physical, psychological, and social changes that can affect the quality of life of individuals. It can represent both an opportunity for society (people gain increased experience) and a threat (due to the high costs to families associated with dementia, as well as limited medical resources).(p1) The aging process is associated with decreased function of organs and systems, leading to various diseases and health problems.(p3),(p4),(p5)
Brain aging is characterized by physiological, structural, and functional modifications, culminating in cognitive decline and a heightened susceptibility to develop neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD).(p4) However, there are multiple factors during fetal development and childhood, and throughout the living adult lifespan, which promote, intensify, or even protect against the pathophysiologic processes that lead to neurodegeneration and its consequent clinical expression.(p3),(p4),(p5) These factors, some of which are negative, may operate together, hampering their investigation on an individual basis.(p4),(p5),(p6),(p7)
The research on cognitive decline demonstrates how important cognition is. Cognition includes functions like memory, attention, perception, and language, among others,(p1) and encompasses the acquisition, storage, manipulation, and use of information. With aging, cognition is commonly compromised. For instance, processing speed decreases, as well as working memory and the ability to multitask.(p1) With the increasing number of elderly persons, it has become important to investigate the effects of the aging process on cognition to develop cognitive-behavioral interventions and public health policies, including preventive psychological therapeutic strategies.(p6),(p8) These strategies are expected to promote healthy aging, improve the quality of life of elderly people, and reduce the risk of dementia development.(p8) However, for this emergent field to achieve maximum development and benefit, it is essential to address major unanswered questions.(p9)
In this context, the current monography aimed to provide a comprehensive overview of existing conceptual models of cognitive reserve and resilience, along with their associated mechanisms. Additionally, it endeavors to investigate the pivotal determinants impacting cognitive resilience and clarify the mechanisms. In parallel, the molecular attributes responsible for preserving cognitive function are critically discussed herein to highlight their potential as therapeutic targets for both neurodegenerative disorders and healthy aging.
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