About this Research Topic
Aging is an inherent process in all living organisms, and cognitive functions show a natural decline with age. Cerebral energy metabolism declines with age, as a result of declining neural and central metabolic control, atrophy of the hypothalamus, and of the orexinergic nucleus. However, there is a continuum between normal aging and neurodegeneration, with fragmented mitochondria, a decrease in the synthesis of sirtuins, failure of proteostasis, and accumulation of toxic proteins being described even in elderly individuals with preserved cognitive functions. Moreover, too low, or excessive neuronal activity may both be destructive, impairing cellular energy metabolism. Low levels of reactive oxygen species act as signaling molecules and promote pro-survival pathways, while high levels lead to oxidative stress and ignite a series of pathophysiological cascades which lead to neuronal degeneration. The involvement of chronic inflammation and astrocytic dysfunction, as well as the weakening of the blood-brain barrier, adds to the complexity of the problem.
Clinically, some individuals reach old and very old ages and remain intellectually active, with no decline in the quality of life, while others develop neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, or other forms of dementia. Genetic factors are involved in the pathogenesis only in a small percentage of cases. Meanwhile, accumulation of toxic proteins (beta-amyloid, synuclein, or other proteins), fragmented mitochondria, or markers of oxidative damage is described in both cognitively impaired and unimpaired elderly individuals. A very interesting question this Research Topic aims to answer is how much these molecular pathways overlap and at what point something goes wrong and aging converts to cognitive impairment or dementia. Elucidating what is normal and why several pathways turn towards pathological and disturb the entire cerebral network would be a huge step forward in preventing or delaying the onset of neurodegenerative diseases and improving the quality of life of the elderly.
Keywords: Brain Aging, Neurodegeneration, Cellular Mechanisms, Molecular Mechanisms, Dementia
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