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      The impact of dietary protein intake on longevity and metabolic health

      review-article
      Author(s): a , b , * , a , a , a , b , *
      Publication date (Electronic):
      Journal: EBioMedicine
      Publisher: Elsevier
      Keywords: Low protein intake, Low-protein/high-carbohydrate diet, Methionine, Branched-chain amino acids, Red meat, Longevity, Metabolic health, mTORC1, mechanistic target of rapamycin complex 1, LPD, low protein diet, LPHC, low protein/high carbohydrate, Met, methionine, Leu, leucine, Arg, arginine, BCAAs, branched-chain amino acids, MetR, methionine restriction, SAM, S-adenosylmethionine, Gnmt, glycine-N-methyltransferase, GH/IGF-1, growth hormone/insulin-like growth factor-1, ROS, reactive oxygen species, EAAs, essential amino acids, NEAAs, nonessential amino acids, Cys, cysteine, tRNA, transfer ribonucleic acid, GCN2, general amino acid control nonderepressible-2, elF2α, eukaryotic initiation factor 2α, ATF, activating transcriptional factor, FGF21, fibroblast growth factor 21, TSP, transsulfuration pathway, CBS, cystathionine β-synthase, CGL, cystathionine γ-lyase, NUPR1, nuclear protein 1, H2S, hydrogen sulphate, Metyl-PP2A, methylated-phosphatase 2A, CASTOR1, cytosolic arginine sensor for mTORC1 subunit 1, GATOR1 and 2, GAP activity towards the Rags 1 and 2, NADPH oxidase, nicotinamide adenine dinucleotide phosphate oxidase, NF-κB, nuclear factor-κ B, DASH, Dietary Approaches to Stop Hypertension

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          Abstract

          Lifespan and metabolic health are influenced by dietary nutrients. Recent studies show that a reduced protein intake or low-protein/high-carbohydrate diet plays a critical role in longevity/metabolic health. Additionally, specific amino acids (AAs), including methionine or branched-chain AAs (BCAAs), are associated with the regulation of lifespan/ageing and metabolism through multiple mechanisms. Therefore, methionine or BCAAs restriction may lead to the benefits on longevity/metabolic health. Moreover, epidemiological studies show that a high intake of animal protein, particularly red meat, which contains high levels of methionine and BCAAs, may be related to the promotion of age-related diseases. Therefore, a low animal protein diet, particularly a diet low in red meat, may provide health benefits. However, malnutrition, including sarcopenia/frailty due to inadequate protein intake, is harmful to longevity/metabolic health. Therefore, further study is necessary to elucidate the specific restriction levels of individual AAs that are most effective for longevity/metabolic health in humans.

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          Sestrin2 is a leucine sensor for the mTORC1 pathway.

          Rachel Wolfson, Lynne Chantranupong, Robert Saxton … (2016)
          Leucine is a proteogenic amino acid that also regulates many aspects of mammalian physiology, in large part by activating the mTOR complex 1 (mTORC1) protein kinase, a master growth controller. Amino acids signal to mTORC1 through the Rag guanosine triphosphatases (GTPases). Several factors regulate the Rags, including GATOR1, aGTPase-activating protein; GATOR2, a positive regulator of unknown function; and Sestrin2, a GATOR2-interacting protein that inhibits mTORC1 signaling. We find that leucine, but not arginine, disrupts the Sestrin2-GATOR2 interaction by binding to Sestrin2 with a dissociation constant of 20 micromolar, which is the leucine concentration that half-maximally activates mTORC1. The leucine-binding capacity of Sestrin2 is required for leucine to activate mTORC1 in cells. These results indicate that Sestrin2 is a leucine sensor for the mTORC1 pathway.
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            Amino acid signalling upstream of mTOR.

            Jenna L. Jewell, Ryan C Russell, Kun-Liang Guan (2013)
            Mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that is part of mTOR complex 1 (mTORC1), a master regulator that couples amino acid availability to cell growth and autophagy. Multiple cues modulate mTORC1 activity, such as growth factors, stress, energy status and amino acids. Although amino acids are key environmental stimuli, exactly how they are sensed and how they activate mTORC1 is not fully understood. Recently, a model has emerged whereby mTORC1 activation occurs at the lysosome and is mediated through an amino acid sensing cascade involving RAG GTPases, Ragulator and vacuolar H(+)-ATPase (v-ATPase).
            Article 0 comments Cited 323 times – based on 0 reviews     Review now
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              Rapamycin slows aging in mice.

              John Wilkinson, Lisa Burmeister, Susan V. Brooks … (2012)
              Rapamycin increases lifespan in mice, but whether this represents merely inhibition of lethal neoplastic diseases, or an overall slowing in multiple aspects of aging is currently unclear. We report here that many forms of age-dependent change, including alterations in heart, liver, adrenal glands, endometrium, and tendon, as well as age-dependent decline in spontaneous activity, occur more slowly in rapamycin-treated mice, suggesting strongly that rapamycin retards multiple aspects of aging in mice, in addition to any beneficial effects it may have on neoplastic disease. We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects of this kind will guide further studies on timing, dosage, and tissue-specific actions of rapamycin relevant to the development of clinically useful inhibitors of TOR action. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
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                Author and article information

                Contributors
                Munehiro Kitada
                Daisuke Koya
                Journal
                Journal ID (nlm-ta): EBioMedicine
                Journal ID (iso-abbrev): EBioMedicine
                Title: EBioMedicine
                Publisher: Elsevier
                ISSN (Electronic): 2352-3964
                Publication date PMC-release: 08 April 2019
                Publication date Collection: May 2019
                Publication date (Electronic): 08 April 2019
                Volume: 43
                Pages: 632-640
                Affiliations
                [a ]Department of Diabetology and Endocrinology, Kanazawa Medical University, Japan
                [b ]Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan
                Author notes
                [* ]Corresponding authors at: Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. kitta@ 123456kanazawa-med.ac.jp koya0516@ 123456kanazawa-med.ac.jp
                Article
                Publisher ID: S2352-3964(19)30239-7
                DOI: 10.1016/j.ebiom.2019.04.005
                PMC ID: 6562018
                PubMed ID: 30975545
                SO-VID: 684db53d-2f2e-4781-b433-023ab0331741
                Copyright © © 2019 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 23 January 2019
                Date revision received : 13 March 2019
                Date accepted : 2 April 2019
                Categories
                Subject: Review

                Keywords: low protein intake,low-protein/high-carbohydrate diet,methionine,branched-chain amino acids,red meat,longevity,metabolic health,mtorc1, mechanistic target of rapamycin complex 1,lpd, low protein diet,lphc, low protein/high carbohydrate,met, methionine,leu, leucine,arg, arginine,bcaas, branched-chain amino acids,metr, methionine restriction,sam, s-adenosylmethionine,gnmt, glycine-n-methyltransferase,gh/igf-1, growth hormone/insulin-like growth factor-1,ros, reactive oxygen species,eaas, essential amino acids,neaas, nonessential amino acids,cys, cysteine,trna, transfer ribonucleic acid,gcn2, general amino acid control nonderepressible-2,elf2α, eukaryotic initiation factor 2α,atf, activating transcriptional factor,fgf21, fibroblast growth factor 21,tsp, transsulfuration pathway,cbs, cystathionine β-synthase,cgl, cystathionine γ-lyase,nupr1, nuclear protein 1,h2s, hydrogen sulphate,metyl-pp2a, methylated-phosphatase 2a,castor1, cytosolic arginine sensor for mtorc1 subunit 1,gator1 and 2, gap activity towards the rags 1 and 2,nadph oxidase, nicotinamide adenine dinucleotide phosphate oxidase,nf-κb, nuclear factor-κ b,dash, dietary approaches to stop hypertension
                Data availability:
                Keywords: low protein intake, low-protein/high-carbohydrate diet, methionine, branched-chain amino acids, red meat, longevity, metabolic health, mtorc1, mechanistic target of rapamycin complex 1, lpd, low protein diet, lphc, low protein/high carbohydrate, met, methionine, leu, leucine, arg, arginine, bcaas, branched-chain amino acids, metr, methionine restriction, sam, s-adenosylmethionine, gnmt, glycine-n-methyltransferase, gh/igf-1, growth hormone/insulin-like growth factor-1, ros, reactive oxygen species, eaas, essential amino acids, neaas, nonessential amino acids, cys, cysteine, trna, transfer ribonucleic acid, gcn2, general amino acid control nonderepressible-2, elf2α, eukaryotic initiation factor 2α, atf, activating transcriptional factor, fgf21, fibroblast growth factor 21, tsp, transsulfuration pathway, cbs, cystathionine β-synthase, cgl, cystathionine γ-lyase, nupr1, nuclear protein 1, h2s, hydrogen sulphate, metyl-pp2a, methylated-phosphatase 2a, castor1, cytosolic arginine sensor for mtorc1 subunit 1, gator1 and 2, gap activity towards the rags 1 and 2, nadph oxidase, nicotinamide adenine dinucleotide phosphate oxidase, nf-κb, nuclear factor-κ b, dash, dietary approaches to stop hypertension

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