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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.

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  • Authors+Show Affiliations

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    Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA.

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    Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.

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    Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.

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    Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.

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    Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.

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    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.

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    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.

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    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.

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    Universidad San Francisco de Quito & Instituto IEMYR, Quito 17-1200-841, Ecuador.

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    Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.

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    Department of Biology, Ecology and Earth Science, University of Calabria, Rende 87036, Italy.

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    Buck Institute for Research on Aging, Novato, CA 94945, USA.

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    Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.

    ,

    Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University of Southern California, Los Angeles, CA 90033, USA.

    ,

    Davis School of Gerontology, University of Southern California, Los Angeles, CA 90033, USA.

    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.

    Source

    Cell metabolism 19:3 2014 Mar 04 pg 407-17

    MeSH

    Aged
    Animals
    Breast Neoplasms
    Carrier Proteins
    Cross-Sectional Studies
    Diabetes Mellitus
    Diet, Protein-Restricted
    Female
    Follow-Up Studies
    Humans
    Insulin-Like Growth Factor I
    Longevity
    Male
    Melanoma
    Mice
    Mice, Inbred BALB C
    Mice, Inbred C57BL
    Mice, Knockout
    Middle Aged
    Neoplasms
    Proportional Hazards Models
    Signal Transduction

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24606898

    Citation

    Levine, Morgan E., et al. "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." Cell Metabolism, vol. 19, no. 3, 2014, pp. 407-17.
    Levine ME, Suarez JA, Brandhorst S, et al. 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. Cell Metab. 2014;19(3):407-17.
    Levine, M. E., Suarez, J. A., Brandhorst, S., Balasubramanian, P., Cheng, C. W., Madia, F., ... Longo, V. D. (2014). 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. Cell Metabolism, 19(3), pp. 407-17. doi:10.1016/j.cmet.2014.02.006.
    Levine ME, et al. 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. Cell Metab. 2014 Mar 4;19(3):407-17. PubMed PMID: 24606898.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - Levine,Morgan E, AU - Suarez,Jorge A, AU - Brandhorst,Sebastian, AU - Balasubramanian,Priya, AU - Cheng,Chia-Wei, AU - Madia,Federica, AU - Fontana,Luigi, AU - Mirisola,Mario G, AU - Guevara-Aguirre,Jaime, AU - Wan,Junxiang, AU - Passarino,Giuseppe, AU - Kennedy,Brian K, AU - Wei,Min, AU - Cohen,Pinchas, AU - Crimmins,Eileen M, AU - Longo,Valter D, PY - 2013/12/04/received PY - 2014/01/24/revised PY - 2014/02/10/accepted PY - 2014/3/11/entrez PY - 2014/3/13/pubmed PY - 2014/11/5/medline SP - 407 EP - 17 JF - Cell metabolism JO - Cell Metab. VL - 19 IS - 3 N2 - 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. SN - 1932-7420 UR - https://www.unboundmedicine.com/medline/citation/24606898/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S1550-4131(14)00062-X DB - PRIME DP - Unbound Medicine ER -