Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.

Co-evolution of mammals and their gut microbiota has profoundly effected their radiation into myriad habitats. We used shotgun sequencing of microbial community DNA and targeted sequencing of bacterial 16S rRNA genes to understand how microbial communities adapt to extremes of diets, sampling fecal DNAs from 33 mammalian species and 18 humans who kept detailed diet records. We found that microbiota adaptation to diet is reproducible across different mammalian lineages. Functional repertoires of microbiome genes, such as those encoding carbohydrate-active enzymes and proteases, can be predicted from bacterial species assemblages. These results illustrate the value of characterizing vertebrate gut microbiomes to fully understand host evolutionary histories at a supra-organismal level.

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.