Table 1.

Experiments on a range of organisms exploring CR, protein restriction and macronutrient balance.

Animal	lifespan increase	beneficial health effects	Reproductive effects	Reference
Caloric restriction
Yeast	Increase in mean and maximum lifespan with glucose depletion	Increased mitochondrial respiration	Biomass production impaired on low glucose treatments	Lin, et al. (2004); Wu, et al. (2013); Bonawitz et al. (2007)
Worms	Up to 50% with bacteria-free media	Increase oxidative and thermal stress resistance	Number of eggs laid per worm increased	Hosono, et al. (1989); Houthoofd, et al. (2002)
Flies	Up to 50% at 40% CR	Not reported	Egg production decreased with CR	Partridge et al. (2005)
Rhesus Monkeys	Trend seen. Conflicting results about lifespan extension	Delay in age-related disease, improved metabolic health and decrease in cancer. Reduction in cardiovascular disease and brain atrophy	Unknown	Colman et al. (2009); Mattison et al. (2012)
Humans	Unknown	Reduced risk of age-related disease such as diabetes, stoke, cardiovascular disease, obesity, metabolic disorders, cancer.	Late reproductive maturity, suppressed ovarian function, impaired fecundity	Fontana and Klein (2007); Heilbronn and Ravussin (2003); Mercken, et al. (2012)
Protein restriction
Flies	Yeast-restricted flies also show median and maximal lifespan extension.	Not reported	CR reduces lifetime fecundity.	Grandison et al. (2009); Mair et al. (2005)
Mice	Maximal lifespan extended by methionine restriction	Reduced IGF-1, insulin, glucose and thyroid hormone levels. Delayed immune impairment and cataracts	Not reported	Miller et al. (2005)
Rats	Mean and maximal lifespan extended by methionine restriction	Reduced body weight	Not reported	Richie et al. (1994)
Humans	Decreased mortality by 25% in people aged 50-65. Higher protein intake associated with reduced mortality in people over 65.	Four-fold decrease in cancer death risk in people aged 50-65. Five-fold decrease in diabetes overall.	Not reported	Levine et al. (2014)
Macronutrient balance
Flies	3 fold on diets with a low protein to carbohydrate ratio	Increased triglyceride storage on low protein diets	Higher protein to carbohydrate ratios optimized reproduction	Lee et al. (2008); Fanson et al. (2009); Jensen et al. (2015); Bruce et al. (2013) ; Skorupa, et al. (2008)
Crickets	Up to 3.5 fold on diets with a low protein to carbohydrate ratio	Not reported	Responses vary by sex. Reproduction optimized at higher protein to carbohydrate ratios females only.	Maklakov et al. (2008)
Mice	~30% on diets with a low protein to carbohydrate ratio	Improved blood pressure, lipid profiles, mitochondrial function, insulin sensitivity, HOMA and immune function	Reproduction optimized in diets with a higher protein to carbohydrate ratio compared to lifespan	Solon-Biet et al. (2014); Solon-Biet et al. (2015a) Solon-Biet et al. (2015b); Le Couteur et al. (2014)