Nutrients and Pathways that Regulate Health Span and Life Span

Abstract

Both life span and health span are influenced by genetic, environmental and lifestyle factors. With the genetic influence on human life span estimated to be about 20–25%, epigenetic changes play an important role in modulating individual health status and aging. Thus, a main part of life expectance and healthy aging is determined by dietary habits and nutritional factors. Excessive or restricted food consumption have direct effects on health status. Moreover, some dietary interventions including a reduced intake of dietary calories without malnutrition, or a restriction of specific dietary component may promote health benefits and decrease the incidence of aging-related comorbidities, thus representing intriguing potential approaches to improve healthy aging. However, the relationship between nutrition, health and aging is still not fully understood as well as the mechanisms by which nutrients and nutritional status may affect health span and longevity in model organisms. The broad effect of different nutritional conditions on health span and longevity occurs through multiple mechanisms that involve evolutionary conserved nutrient-sensing pathways in tissues and organs. These pathways interacting each other include the evolutionary conserved key regulators mammalian target of rapamycin, AMP-activated protein kinase, insulin/insulin-like growth factor 1 pathway and sirtuins. In this review we provide a summary of the main molecular mechanisms by which different nutritional conditions, i.e., specific nutrient abundance or restriction, may affect health span and life span.

Comparative Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs Ketosis-Inducing Diet

“…Calorie Restriction (CR) is a nutritional intervention of reduced energy intake of about 25-30% without lack of essential nutrients [1], with a well-established role to extend health span and lifespan in rodent and primate models. Throughout the literature, CR is often used interchangeably with Dietary Restriction (DR).…”

“…Throughout the literature, CR is often used interchangeably with Dietary Restriction (DR). However, CR is a partial example of DR as DR protocols include CR, reduction of specific macronutrients or change in the ratio of them as well as other different feeding interventions, such as ketosis-inducing diets [1].…”

“…Calorie Restriction is the most robust intervention known until the moment to increase maximal lifespan and health span in large studies, with high evidence, biological plausibility and explained biochemical mechanisms [1]. Among the various mechanisms described are adaptive neuroendocrine responses, hormetic responses, modulation of the inflammatory response and the redox system.…”

“…Taken together, these issues raise crucial questions on how we can improve health from a young age, and consequently, improve the quality of life, healthy aging and lifespan. It is known that adequate nutrition is correlated with good health [1,2]. Therefore, it is crucial to understand how different diets can affect health and lifespan, and how can different dietary approaches reduce the risk of developing Chronic Non-Communicable Diseases (CNCD).…”

“…Therefore, it is crucial to understand how different diets can affect health and lifespan, and how can different dietary approaches reduce the risk of developing Chronic Non-Communicable Diseases (CNCD). To date, evidence has shown that a reduced caloric intake, without malnutrition, represents the most robust intervention to increase life span in model organisms, including primates, and to delay the emergence of age-related diseases [1]. Nevertheless, other dietary approaches, such as fasting and ketogenic diets, are emerging with compelling adherence, and therefore the need to understand their various impacts on health span and lifespan.…”