Rodent diet aids and the fallacy of caloric restriction

• Published in: Mechanisms of ageing and development Vol. 200; p. 111584
• Main Author: Wolf, Alexander M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-12-2021
• Subjects: Aging; Aging - physiology; Animals; Caloric Restriction; Caloric restriction mimetics; Energy Intake - physiology; Healthy Aging - physiology; Humans; Life span; Longevity - drug effects; Mice; Obesity; Obesity - diet therapy; Obesity - drug therapy; Obesity - metabolism; Obesity - mortality; Senotherapeutics - pharmacology; Survival Analysis; Aging; Obesity; Life span; Caloric restriction mimetics; Caloric restriction
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2021.111584

•Caloric restriction extends life span mostly by reducing excess mortality due to obesity.•Most pharmacologic interventions to slow aging, including resveratrol, rapamycin, NAD + and metformin, also cause weight loss.•Dietary restriction and weight loss is beneficial only for obese subjects.•Investigating mechanisms of caloric restriction will not help prevent or slow aging in healthy weight humans.
Understanding the molecular mechanisms of normal aging is a prerequisite to significantly improving human health span. Caloric restriction (CR) can delay aging and has served as a yardstick to evaluate interventions extending life span. However, mice given unlimited access to food suffer severe obesity. Health gains from CR depend on control mice being sufficiently overweight and less obese mouse strains benefit far less from CR. Pharmacologic interventions that increase life span, including resveratrol, rapamycin, nicotinamide mononucleotide and metformin, also reduce body weight. In primates, CR does not delay aging unless the control group is eating enough to suffer from obesity-related disease. Human survival is optimal at a body mass index achievable without CR, and the above interventions are merely diet aids that shouldn’t slow aging in healthy weight individuals. CR in humans of optimal weight can safely be declared useless, since there is overwhelming evidence that hunger, underweight and starvation reduce fitness, survival, and quality of life. Against an obese control, CR does, however, truly delay aging through a mechanism laid out in the following tumor suppression theory of aging.