Dear Colleagues,

Aging is a physiological process which includes changes at all levels of the biological organization that are counterbalanced by adaptive response mechanisms produced to preserve the composition and function within homeostatic balance. The aging process produces a deterioration of different patterns of body structure and functions, but the most critical compartment involved is brain, where a dysfunction can lead to neural disability. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. The functional decline associated with normal brain aging is mostly associated with genomic instability, telomere attrition, epigenetic alterations, loss of protein homeostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, and stem cell exhaustion causing neurodegenerative disorders. Therefore, an aging brain in good health is in any case characterized by decline in neuronal activity and loss of synaptic connection and function. In this context, some interventions can slow down physiological and pathological progression through their antioxidant, anti-inflammatory, and antiamyloidogenic properties, regulating mitochondrial stress, apoptotic factors, free radical scavenging system, and neurotrophic factors. For example, the use of nutraceutical molecules (such as vitamin D3, ginger, and lipoic acid) is known to exert beneficial effects on the brain. Indeed, some phytomolecules, like polyphenols, are able to cross the blood–brain barrier (BBB) and act with a protective role against oxidative stress and autophagic pathways and can modulate apoptosis and survival pathways of neurons. On the other hand, the brain-derived neurotrophic factor (BDNF) can be considered as a marker for the development, maintenance, and plasticity of the central and peripheral nervous systems. BDNF promotes the differentiation of neurons from stem cells, and it can prevent programmed cell death/apoptosis. Moreover, emerging findings suggest that BDNF is a master regulator of energetic homeostasis. Natural products and synthetic drugs could stimulate BDNF production, or activate its receptor TrkB, to prevent and treat metabolic and brain disorders connected with aging.

Even if aging is a physiological problem, recent findings suggest that age-related neurodegenerative disorders could be slowed down; it is, therefore, important to continue to pursue novel approaches for the implementation of new compounds able to make old age less debilitating.

Dr. Francesca Uberti
Guest Editor

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• Neurotrophic factors
• Brain aging
• Food supplements
• Neuronal molecular pathways