食物宏量营养素组成调控哺乳动物寿命的研究进展

Abstract

<p indent="0mm">The aging population is one of the world’s most momentous challenges and causes prodigious economic burdens to individuals, families, and a country. As the average lifespan has dramatically increased globally, more people are paying particularly close attention to what/how dietary composition has the potential to extend a healthy lifespan. People have been interested in looking for the elixir of youth, yet studies on molecular mechanisms of aging are relatively new and are far from being understood. Recent work has shown that nutrients, small molecules, genetic modifications, and other factors can substantially extend the lifespan of multispecies, ranging from yeast to mammals. Among these longevity factors, nutrient balance has emerged as an important factor in extending lifespan. Yet, the effect of many nutrient factors on longevity is not well investigated. Most anti-aging studies focus on dietary restriction (DR) or calorie restriction (CR), the mere reduction of food intake without malnutrition, which has become a gold standard in biological aging studies. DR was found to extend the average and maximum lifespan from yeast to primates. It also protects against age-related pathologies, such as diabetes, cancer, and cardiovascular disease in humans. However, studies have shown that changing the dietary components could eliminate lifespan extension by DR, suggesting that nutrient balance other than DR plays a pivotal role in regulating longevity. Notably, mammalian models, mainly rats and mice, have been influential in advancing aging research. Here, we reviewed studies published since 1935 that demonstrated that changing the composition of food macronutrients (carbohydrate, protein or amino acids, and fat) altered lifespan in mouse and rat models. Carbohydrate research has primarily focused on early DR studies, in which researchers used carbohydrates in food to control animal growth and energy intake. Protein/amino acids may significantly impact lifespan more than carbohydrates and fats because growth and development depend more on protein intake in the early stages of life. However, protein requirement decreases in mature animals, and excessive protein consumption stimulates growth and differentiation, which may accelerate aging. In mammals, reducing protein intake reduces body weight, increases physical activity, and prolongs lifespan. On the other hand, studies primarily focused on essential amino acids such as methionine, glycine, tryptophan, BCAA, and the non-essential amino acid arginine that alter mammalian metabolism and aging through various mechanisms that influence lifespan. The type of fat, the sexual activities, genetics, environment, and health status of the study subjects all influence whether and how changes in dietary fat content affect lifespan. Recently, dietary supplementation of P꞉C has become an emerging research topic, with most studies concluding that a diet low in P꞉C benefits longevity. Likewise, the ketogenic diet (KD) is a brand-new diet that has only recently emerged and is frequently used as an alternative for treating epilepsy and other diseases. Although it may increase patient survival time, it has not been known to extend life expectancy in healthy populations effectively. Moreover, the effect of these nutrients on lifespan may be generally influenced by the subjects’ age and health status. In conclusion, the three macronutrients significantly impact mammalian longevity and may eventually replace DR as the key to dietary recommendations for human longevity. Therefore, a key focus of future research on longevity is needed to thoroughly and meticulously reveal the molecular mechanisms by which macronutrients affect lifespan. These dietary composition-related longevity interventions and the associated tools could provide new insights into studying healthy longevity.