title: 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.
abstract: 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.
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Levine
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Suarez
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandhorst
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Balasubramanian
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; EURL ECVAM, Institute for Health & Consumer Protection, European Commission Joint Research Centre, Ispra (VA) 21027, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Madia
authors.affiliation: Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Clinical and Experimental Sciences, Brescia University School of Medicine, Brescia 25123, Italy; CEINGE Biotecnologie Avanzate, Napoli 80145, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA; Dipartimento di Biopatologia e Metodologie Biomediche, Universita' di Palermo, Palermo 90127, Italy.
authors.forename: Mario G
authors.initials: MG
authors.lastname: Mirisola
authors.affiliation: Universidad San Francisco de Quito & Instituto IEMYR, Quito 17-1200-841, Ecuador.
authors.forename: Jaime
authors.initials: J
authors.lastname: Guevara-Aguirre
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Junxiang
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Biology, Ecology and Earth Science, University of Calabria, Rende 87036, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kennedy
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Pinchas
authors.initials: P
authors.lastname: Cohen
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Crimmins
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: vlongo@usc.edu.
authors.forename: Valter D
authors.initials: VD
authors.lastname: Longo
mesh_terms: D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000401:mortality; D018753:Diet, Protein-Restricted; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity; D008297:Male; D008545:Melanoma / Q000209:etiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009369:Neoplasms / Q000178:diet therapy* / Q000453:epidemiology / Q000401:mortality; D016016:Proportional Hazards Models; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein