Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population

• Published in: Cell metabolism 2014-03, Vol.19 (3), p.407-417
• Main Authors: Levine, Morgan E., Suarez, Jorge A., Brandhorst, Sebastian, Balasubramanian, Priya, Cheng, Chia-Wei, Madia, Federica, Fontana, Luigi, Mirisola, Mario G., Guevara-Aguirre, Jaime, Wan, Junxiang, Passarino, Giuseppe, Kennedy, Brian K., Wei, Min, Cohen, Pinchas, Crimmins, Eileen M., Longo, Valter D.
• Format: Article
• Language: English
• Subjects: Aged; Animals; Breast Neoplasms - etiology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cross-Sectional Studies; Diabetes Mellitus - mortality; Diet, Protein-Restricted; Female; Follow-Up Studies; Humans; Insulin-Like Growth Factor I - metabolism; Longevity; Male; Melanoma - etiology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Neoplasms - diet therapy; Neoplasms - epidemiology; Neoplasms - mortality; Proportional Hazards Models; Signal Transduction
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2014.02.006

Mice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages. Mouse studies confirmed the effect of high protein intake and GHR-IGF-1 signaling on the incidence and progression of breast and melanoma tumors, but also the detrimental effects of a low protein diet in the very old. These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize healthspan and longevity. [Display omitted] •High protein intake is linked to increased cancer, diabetes, and overall mortality•High IGF-1 levels increased the relationship between mortality and high protein•Higher protein consumption may be protective for older adults•Plant-derived proteins are associated with lower mortality than animal-derived proteins The effect of dietary composition on lifespan is a key question. Levine et al. show that high animal protein intake in middle-aged humans was associated with overall mortality, cancer, and diabetes, but in people aged 65 and above, high protein intake was associated with reduced cancer and overall mortality.