Promoting Health and Longevity through Diet: From Model Organisms to Humans

Abstract

Reduced food intake, avoiding malnutrition, can ameliorate aging and aging-associated diseases in invertebrate model organisms, rodents, primates and humans. Recent findings indicate that meal timing is crucial, with both intermittent fasting and adjusted diurnal rhythm of feeding improving health and function, in the absence of changes in overall intake. Lowered intake of particular nutrients, rather than of overall calories, is also key, with protein and specific amino acids playing prominent roles. Nutritional modulation of the microbiome can also be important, and there are long-term, including inter-generational, effects of diet. The metabolic, molecular and cellular mechanisms that mediate the responses of health during aging to diet, and genetic variation in response to diet, are being identified. These new findings are opening the way to specific dietary and pharmacological interventions to recapture the full potential benefits of dietary restriction, which humans can find hard to maintain voluntarily.

Gene expression‐based drug repurposing to target aging

“…Many of these interventions target components of the nutrient‐sensing network and decrease the activity of IGF/insulin and/or TOR signalling (Fontana, Partridge, & Longo, 2010). Moreover, dietary restriction (DR), decreased food intake without malnutrition, can increase lifespan and further supports the importance of nutrient‐sensing pathways in aging (Fontana & Partridge, 2015). …”

The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon

“…While genetic manipulations of model organisms have set important milestones for the understanding of the aging process, calorie restriction (CR) is a well‐established nongenetic approach able to improve health span and lifespan in different organisms (Finkel, 2015). However, the precise mechanisms by which CR improves health are not fully understood (Speakman & Mitchell, 2011; Fontana & Partridge, 2015). …”

“…Calorie restriction is a potent intervention for delaying aging and age‐related pathologies, but the factors determining these effects are largely unknown (Fontana & Partridge, 2015). The reduced expression of markers of senescence in both humans and mice is an intriguing mechanism that could further explain the potential beneficial effects of CR.…”

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

“…Apart from life‐span, reduced food intake also increases health‐span. Here, the health‐promoting effect is not achieved by counteracting obesity‐related disorders, but by ameliorating a wide range of aging‐related diseases 5, 6, 7. It is worth mentioning, however, that these obesity‐ and age‐related disorders fundamentally overlap.…”