The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

Abstract

Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) and neurodegenerative disorders. The debilitating effects of metabolic disorders influence the entire body and significantly affect the nervous system impacting greater than one billion people with disability in the peripheral nervous system as well as with cognitive loss, now the seventh leading cause of death worldwide. Metabolic disorders, such as DM, and neurologic disease remain a significant challenge for the treatment and care of individuals since present therapies may limit symptoms but do not halt overall disease progression. These clinical challenges to address the interplay between metabolic and neurodegenerative disorders warrant innovative strategies that can focus upon the underlying mechanisms of aging-related disorders, oxidative stress, cell senescence, and cell death. Programmed cell death pathways that involve autophagy, apoptosis, ferroptosis, and pyroptosis can play a critical role in metabolic and neurodegenerative disorders and oversee processes that include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, and inflammatory cell activation. The silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), AMP activated protein kinase (AMPK), and Wnt1 inducible signaling pathway protein 1 (WISP1) are novel targets that can oversee programmed cell death pathways tied to β-nicotinamide adenine dinucleotide (NAD+), nicotinamide, apolipoprotein E (APOE), severe acute respiratory syndrome (SARS-CoV-2) exposure with coronavirus disease 2019 (COVID-19), and trophic factors, such as erythropoietin (EPO). The pathways of programmed cell death, SIRT1, AMPK, and WISP1 offer exciting prospects for maintaining metabolic homeostasis and nervous system function that can be compromised during aging-related disorders and lead to cognitive impairment, but these pathways have dual roles in determining the ultimate fate of cells and organ systems that warrant thoughtful insight into complex autofeedback mechanisms.

Natural products targeting autophagy and apoptosis in NSCLC: a novel therapeutic strategy

“…“ACD” is characterized by abundant autophagosomes and autophagolysosomes in the cytoplasm, extensive cytoplasmic degradation, but an intact nucleus, typically not reliant on Caspase family activity ( 137 , 138 ). The concept of autophagy-related cell death is debated, as autophagy-mediated apoptosis and a distinct cell death mechanism (independent of apoptosis and necrosis) are all referred to as “ACD” ( 139 ). Whether autophagy promotes or inhibits apoptosis depends on the cell type, stress nature, and stress duration ( 140 ).…”

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome

“…This may lead to a less efficient oxidative phosphorylation process, resulting in the production of more free radicals and reactive oxygen species (ROS) ( Reid et al, 2018 ). ROS are a hallmark of oxidative stress and they can damage intracellular proteins, lipids, and DNA, leading to impairment of cellular function and structure, which has been implicated in the development of a variety of diseases including aging, diabetes mellitus, vascular endothelial cell injury, neurodegenerative diseases, and the onset of cellular senescence, strategies to replenish depleted NAD + pools can offer significant improvements of pathologic states ( Klimova and Kristian, 2019 ; Maiese, 2023 ). A decrease in NAD + levels directly affects the metabolism of the body’s three major energy substances: sugar, fat, and protein, inducing MetS ( Covarrubias et al, 2021 ).…”

Research progress of SIRTs activator resveratrol and its derivatives in autoimmune diseases

“…Oxidative stress is widely recognized as a major contributor to inflammation and arthritis. An increase in chemical reactions within the body, damage to antioxidant defense systems, and an imbalance between oxidants and antioxidants can lead to a sharp rise in ROS, culminating in the accumulation of reactive oxygen molecules and defects in DNA, RNA, and proteins ( 124 ). Studies have demonstrated that RES effectively scavenges radicals such as hydroxyl and superoxide, thereby inhibiting lipid peroxidation and DNA damage induced by excessive ROS production ( 125 ).…”