Human lifespan depends primarily on genetic, environmental, and lifestyle factors, which affect the risk of illness and survival. The genetic effect on life expectancy in humans is estimated to be about 20-25% and slightly increased after age 60 and probably even higher after age 90. However, most healthy aging and life expectancy are determined by lifestyle and environmental factors. Over the last few decades, improvements in income, nutrition, education, and especially various lifestyle measures such as hygiene, health care, and health care have significantly increased life expectancy for adults of all ages.
Caloric restiction (CR), and lifespanObesity and metabolic syndrome are one of the greatest medical threats to the healthcare system in many countries around the world. There are three simple reasons for this worrying development: overeating, increased stress, and above all, not exercising enough. The inevitable result is a global increase in body mass index (BMI) and waist circumference, which is a significant proportion of the world's population. CR has been shown to extend lifespan and/or reduce various age-related pathologies and risk factors such as obesity, type 2 diabetes, cancer, and neurodegeneration in a variety of organisms, including primates and humans. Extensive studies by the Wisconsin National Center for Primate Research on primate CR showed that a 30% incidence of fasting in adults in rhesus monkeys reduces the incidence of age-related mortality and delays the onset of age-related diseases. Additionally, it was effective and had a positive effect on mortality. So, if you want to practice CR or fasting, it is recommended to use the fasting protocol.
Protein restrictionsIn general, dietary protein intake is known to be an important regulator of the IGF1 / mTOR network, and protein restriction reduces IGF1 levels. IGFBP3 has been associated with reduced tumor-related mortality. In this regard, recent meta-analyses have shown that milk and dairy (protein) intake is positively correlated with circulating IGFI and IGFBP3 levels in almost all studies. It has been confirmed that milk/dairy products (proteins) are being investigated and IGF1 showed a positive association. This can be seen as a specific limitation on milk/milk protein consumption, as suppression of IGF1 is thought to extend lifespan, at least in model organisms.
Role of NAD+In mammals, NAD + is NAD + itself (which is metabolized in the intestine and then resynthesized in cells), including the tryptophan (Trp), nicotinic acid (NA), nicotinamide-riboside (NR), nicotinamide mononucleotide. (NMN) and nicotinamide (NAM). Based on the bioavailability of its precursor, there are three pathways for the synthesis of NAD + in the cell.
(i) From Trp via the de novo biosynthetic pathway or the kynurenine pathway.
(ii) By NA of Preiss handler method.
(iii) From NAM, NR, and NMN of salvage pathways.
Evidence is accumulating that shows age-related declines in NAD + levels and links their depletion to some features of age-related and age-related illnesses. The role of NAD + synthesis and consuming enzymes in aging and age-related diseases is being investigated. Increasing evidence shows that NAD + levels decrease with age in multiple tissue types such as liver, skeletal muscle, adipose tissue, heart, brain, kidneys, pancreas, lungs, spleen, skin, and extracellular fluid. In addition, decreased age-dependent levels of NAD + have been reported in elegans, mouse, and human postmortem tissues. This underscores the universal age-dependent reduction of NAD + in all species. However, it remains unclear whether this is due to increased NAD + consumption and/or decreased synthesis.
Caloric Restriction, and NAD+ LevelsA balanced diet containing macronutrients and micronutrients is the basis of health and well-being. Limiting caloric intake remains a strategy supported by most evidence to ensure a longer lifespan and health. Significant prolongation of lifespan has been reported in various model organisms when calories are limited to 25-60% compared to normal feeding controls.
How is calorie restriction related to NAD + levels?CR stimulates the NAD + salvage pathway, enhances the bioavailability of NAD + by activating NAMPT expression, and triggers the NAD + salvage pathway by converting nicotinamide (NAM) to NAD +. Caloric restriction increases NAD+ levels while lowering NADH levels and activating sirtuins. For example, caloric restriction extends the yeast`s life span by lowering the level of NADH, since NADH is a competitive inhibitor of Sir2. Thus, activation of sirtuins with a sufficient amount of bioavailable NAD+ is a necessary condition for the lifespan extension provided by CR. Specifically, Sirt1 regulates CR by detecting intracellular low energy levels and provoking physiological changes relevant to health and longevity. On the other hand, inactivation of SIRT1 results in the prevention of CR-mediated lifespan extension.
Studies on calorie restriction have shown that improving the ratio of NAD + to NADH is more important than increasing the total amount of NAD + in cells. Indeed, calorie restriction lowers NADH levels more than it affects NAD + levels, at least in yeast. Since NADH is an inhibitor of sirtuins and PARP, a decrease in NADH appears to be an important factor responsible for increased activity of NAD + consuming enzymes. It should be emphasized that NAD + is not the only factor, but one of several factors that affect cell health.
ConclusionMany other beneficial human health effects of calorie restriction, eating habits, exercise, circadian rhythms, and environmental stress are gaining wide spectrum of popularity. Although many animal studies have shown a link between NAD + and healthspan, the complex role of NAD + in the pathogenesis of human aging and age-related chronic diseases is worth further elucidation. Since the current knowledge of the positive health effects of NAD + on aging, beauty, and health is mainly based on cell culture and experiments in model organisms, the positive health effects of NAD + in humans will be discussed in detail in the future. It needs to be confirmed in clinical trials.