“Antiaging Diets: Separating Fact from Fiction”, 2021-11-19 (; similar):
Caloric restriction has been known for nearly a century to extend life span and delay age-associated pathology in laboratory animals. More recently, alternative “antiaging” diet modalities have been described that provide new mechanistic insights and potential clinical applications. These include intermittent fasting, fasting-mimicking diets, ketogenic diets, time-restricted feeding, protein restriction, and dietary restriction of specific amino acids.
Despite mainstream popularization of some of these diets, many questions remain about their efficacy outside of a laboratory setting.
Studies of these interventions support at least partially overlapping mechanisms of action and provide insights into what appear to be highly conserved mechanisms of biological aging.
Caution around the fountain of youth: The scientific and popular literature is full of claims for diets that delay or reverse the aging process (at least in model organisms). But how do these interventions work? Is it the amount of food, the timing of food intake, the proportion of certain macronutrients? In a Review, et al 2021 explore the fact and fiction of dietary prescriptions for a healthier and longer life. They propose that one unifying concept may be convergence on the signaling pathway mediated by the protein kinase mTOR (“mechanistic target of rapamycin”). Another conclusion is that the efficacy and safety of these diets for humans largely remain to be established.
Background: Reduced caloric intake without malnutrition is the oldest known life span-extending intervention. Laboratory studies throughout the 20th century established and confirmed the benefits of caloric restriction (CR) in multiple model systems. CR not only increased life span across evolutionarily distant organisms but also reduced age-associated disease burden and functional decline in these studies. Epidemiological data from human populations is also generally consistent with the idea that lower caloric intake is associated with increased life expectancy. In recent years, numerous diet modalities that are purported to be “antiaging” have sprung from these observations. These diets restrict particular macronutrients (carbohydrates or protein) or feeding intervals and can be divided into those that impose reduced caloric intake versus those that are isocaloric to control diets.
Advances: We evaluated several of the most popular antiaging diets, including CR, intermittent fasting, fasting-mimicking diets, ketogenic diets, time-restricted feeding, protein restriction, and essential amino acid restriction. By characterizing these nutritional interventions in comparison with classical CR, we gained numerous insights. Many studies fail to control for reduced caloric intake in the diet group, making their effects impossible to decouple from CR. Although often presented as uniformly beneficial, the effects of CR on life span are highly dependent on genotype and, in some cases, cause reduced survival. Despite their limitations, these studies have greatly improved our understanding of the cellular response to low nutrient availability. A picture is beginning to emerge of a complex network composed of multiple signaling pathways that converge on key molecular hubs; foremost among these is the mechanistic target of rapamycin (mTOR). Because mTOR and other components of this network are well-studied drug targets, there continues to be considerable interest in pharmacologically targeting this network to increase longevity and health span. Human studies, both correlative and controlled, are consistent with health benefits conferred by a CR diet. However, it remains unresolved whether these benefits are a consequence of modulating the aging process itself or are simply the result of avoiding obesity. Several unresolved questions suggest caution when considering whether to recommend or implement any of these diets among the healthy general public. Among these is understanding how genetic and environmental variation modify diet response, especially in understudied populations and in the context of environmental challenges such as, for example, a global viral pandemic.
Outlook: CR and other antiaging diets have yielded important insights into the complex and evolutionarily conserved signaling pathways that transduce information regarding environmental nutrient availability into a physiological response to promote healthy longevity. This understanding, in turn, has opened the door to a new generation of longevity-promoting interventions that mimic molecular responses to nutrient deprivation. Although CR and other diets hold promise, additional data from carefully controlled studies is needed before broadly recommending or implementing these diets, or other interventions, for otherwise healthy people. Human genetic and environmental variation combined with the challenge of modeling human aging in ultimately dissimilar mammalian model systems pose fundamental limitations to our current ability to predictably translate these findings to people. From a pragmatic perspective, even if these challenges can be overcome, widespread adoption of dietary interventions for healthy longevity seem unrealistic. We therefore suggest that alternative, nondietary strategies with the potential for public uptake should therefore be pursued. In particular, validated biomarkers of biological aging are required to match intervention to each person’s distinct genetic and environmental context and thereby optimize individual healthy life span. Future research directed at clarifying the underlying mechanisms involved in eliciting the longevity-promoting response to CR, and how this differs among individuals, should one day help us realize a true precision geroscience approach.