Horizons in Human Aging Neuroscience: From Normal Neural Aging to Mental (Fr)Agility

Abstract

While aging is an important risk factor for neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease, age-related cognitive decline can also manifest without apparent neurodegenerative changes. In this review, we discuss molecular, cellular, and network changes that occur during normal aging in the absence of neurodegenerative disease. Emerging findings reveal that these changes include metabolic alterations, oxidative stress, DNA damage, inflammation, calcium dyshomeostasis, and several other hallmarks of age-related neural changes that do not act on their own, but are often interconnected and together may underlie age-related alterations in brain plasticity and cognitive function. Importantly, age-related cognitive decline may not be reduced to a single neurobiological cause, but should instead be considered in terms of a densely connected system that underlies age-related cognitive alterations. We speculate that a decline in one hallmark of neural aging may trigger a decline in other, otherwise thus far stable subsystems, thereby triggering a cascade that may at some point also incur a decline of cognitive functions and mental well-being. Beyond studying the effects of these factors in isolation, considerable insight may be gained by studying the larger picture that entails a representative collection of such factors and their interactions, ranging from molecules to neural networks. Finally, we discuss some potential interventions that may help to prevent these alterations, thereby reducing cognitive decline and mental fragility, and enhancing mental well-being, and healthy aging.

Late-Life Bipolar Disorder Subtypes According to Age Onset

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Age-dependent changes in the dynamic functional organization of the brain at rest: a cross-cultural replication approach

“…Therefore, in the future, stringently harmonized cross-cultural datasets are essential to shed light on the magnitude of age-associated changes in differentiated contexts. Seventh, as of yet, the specific molecular drivers responsible for age-associated changes in fMRI metrics remain unknown, although these may include oxidative stress, metabolic alterations, or inflammation ( Ridderinkhof and Krugers 2022 ). Future cross-cultural comparisons of such mechanisms may provide important mechanistic insights into (differences in) biological processes that facilitate age-associated neural changes measured indirectly with fMRI.…”

β-Hydroxybutyrate Regulates Activated Microglia to Alleviate Neurodegenerative Processes in Neurological Diseases: A Scoping Review

“…While longevity is one of the most celebrated modern scientific achievements, it does not necessarily translate into improved healthier living. With advancing age, deleterious changes in the body system are typically associated with deterioration of functionality and increased vulnerability to death, which reduces the overall quality of life [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. This has led to the shift of focus of public policies from prolonging life to improving overall health span [ 9 , 10 , 11 , 12 , 13 ].…”