Metabolic syndrome  (MetSyn)is a dyslipidaemic chronic and aging  linked sedentary life-style constellation of disease presentations including metabolic disorganization, prodromal Type 2 diabetes and a prominent connection to hypertension-most prominently associated with over-eating and obesity. MetSyn is often  prolegomena to middle-age onset CVD, cancer and neurodegeneration. High caloric density soluble carbohydrate nutrition, lack of fasting and the species-specific metabolic inability to convert fatty acids into glucose via gluconeogenesis, provide a pathobiochemical poise toward MetSyn.

As Nicotinamide Adenine Dinucleotide (NAD+) levels decline with age and obesity a potential suppression of NAD (H)-dependent enzymes in oxidative phosphorylation, the TCA cycle, and glycolysis resulting in suppressed  ATP production can trigger the AMPK mediated transcriptional activation of the senescence-associated secretory phenotype (SASP) leading to morbidity and mortality in the advanced aged human.

However, NAD+ essential DNA Damage Repair and Sirtuin-mediated deacetylation of histone-associated chromatin may exacerbate aging and both neurodegeneration and tumorigenesis.

Published and produced by Dr. Daniel J. Guerra, Authentic Biochemistry 17 December 2020.

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