Ukr.Biochem.J. 2021; Volume 93, Issue 1, Jan-Feb, pp. 30-39

doi: https://doi.org/10.15407/ubj93.01.030

Protein intake and loss of proteostasis in the eldery

A. N. Kirana1, E. Prafiantini1, N. S. Hardiany2,3*

1Department of Nutrition, Faculty of Medicine, Universitas Indonesia – Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia;
2Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia;
3Center of Hypoxia and Oxidative Stress Studies, Faculty of Medicine, Universitas Indonesia;
*e-mail: novi.silvia@ui.ac.id

Received: 29 June 2020; Accepted: 17 December 2020

Ageing is a process of declining bodily function and a major risk factor of chronic diseases. The declining bodily function in ageing can cause loss of proteostasis (protein homeostasis), which is a balance between protein synthesis, folding, modification and degradation. For the elderly, adequate protein intake is necessary to prevent sarcopenia, frailty, fracture and osteoporosis as well as reduced resistance to infection. However, increasing the protein intake can enhance the risk of oxidized protein formation, loss of proteostasis and degenerative disorder occurrence. On the other hand, several studies show that protein restriction would increase longevity. The aim of this review was to explain the importance of determining the right amount and composition of protein intake for the elderly. Oxidative stress and molecular mechanism of proteostasis loss in ageing cells as well as its suppression pathway by protein restriction are discussed in this review.

Keywords: , , , ,


References:

  1. United Nations, Department of Economic and Social Affairs. World populations prospects: The 2017 revision, Ky Findings, an Advance Tables. New York: United Nations. ESA/P/WP/248.P.1-10.
  2. Mc Auley MT, Guimera AM, Hodgson D, Mcdonald N , Mooney KM, Morgan AE, Proctor CJ. Modelling the molecular mechanisms of aging. Biosci Rep. 2017;37(1):BSR20160177. PubMed, PubMedCentral, CrossRef
  3. Kirkwood TBL. Understanding the odd science of aging. Cell. 2005;120(4):437-447. PubMed, CrossRef
  4. Kirkwood TBL, Boys RJ, Gillespie CS, Proctor CJ, Shanley DP, Wilkinson DJ. Towards an e-biology of ageing: integrating theory and data. Nat Rev Mol Cell Biol. 2003;4(3):243-249. PubMed, CrossRef
  5. Rattan SIS. Theories of biological aging: genes, proteins, and free radicals. Free Radic Res. 2006;40(12):1230-1238. PubMed, CrossRef
  6. Sergiev PV, Dontsova OA, Berezkin GV. Theories of aging: an ever-evolving field. Acta Naturae. 2015;7(1):9-18. PubMed, PubMedCentral, CrossRef
  7. Jin K. Modern Biological Theories of Aging. Aging Dis. 2010;1(2):72-74. PubMed, PubMedCentral
  8. Grune T, Jung T, Merker K, Davies KJA. Decreased proteolysis caused by protein aggregates, inclusion bodies, plaques, lipofuscin, ceroid, and ‘aggresomes’ during oxidative stress, aging, and disease. Int J Biochem Cell Biol. 2004;36(12):2519-2530. PubMedCrossRef
  9. Suji G, Sivakami S. Glucose, glycation and aging. Biogerontology. 2004;5(6):365-373. PubMed, CrossRef
  10. Harman D. The free radical theory of aging. Antioxid Redox Signal. 2003;5(5):557-561. PubMed, CrossRef
  11. Wang Z, Wang Y, Liu H, Che Y, Xu Y, Lingling E. Age-related variations of protein carbonyls in human saliva and plasma: is saliva protein carbonyls an alternative biomarker of aging? Age (Dordr). 2015;37(3):9781. PubMed, PubMedCentral, CrossRef
  12. Gubandru M, Margina D, Tsitsimpikou C, Goutzourelas N, Tsarouhas K, Ilie M, Tsatsakis AM, Kouretas D. Alzheimer’s disease treated patients showed different patterns for oxidative stress and inflammation markers. Food Chem Toxicol. 2013;61:209-214. PubMed, CrossRef
  13. Mannello F, Ligi D, Canale M. Aluminium, carbonyls and cytokines in human nipple aspirate fluids: Possible relationship between inflammation, oxidative stress and breast cancer microenvironment. J Inorg Biochem. 2013;128:250-256. PubMed, CrossRef
  14. Sefi M, Fetoui H, Makni M, Zeghal N. Mitigating effects of antioxidant properties of Artemisia campestris leaf extract on hyperlipidemia, advanced glycation end products and oxidative stress in alloxan-induced diabetic rats. Food Chem Toxicol. 2010;48(7):1986-1993. PubMed, CrossRef
  15. Pandey KB, Mehdi MM, Maurya PK, Rizvi SI. Plasma protein oxidation and its correlation with antioxidant potential during human aging. Dis Markers. 2010;29(1):31-36. PubMed, PubMedCentral, CrossRef
  16. Baum JI, Kim IY, Wolfe RR. Protein Consumption and the Elderly: What Is the Optimal Level of Intake? Nutrients. 2016;8(6):359. PubMed, PubMedCentral, CrossRef
  17. Wolfe RR. The role of dietary protein in optimizing muscle mass, function and health outcomes in older individuals. Br J Nutr. 2012;108(Suppl 2):S88-S93.  PubMed, CrossRef
  18. Morais JA, Chevalier S, Gougeon R. Protein turnover and requirements in the healthy and frail elderly. J Nutr Health Aging. 2006;10(4):272-283. PubMed
  19. Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft AJ, Morley JE, Phillips S, Sieber C, Stehle P, Teta D, Visvanathan R, Volpi E, Boirie Y. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013;14(8):542-559. PubMed, CrossRef
  20. Baum JI, Wolfe RR. The Link between Dietary Protein Intake, Skeletal Muscle Function and Health in Older Adults. Healthcare (Basel). 2015;3(3):529-543. PubMed, PubMedCentral, CrossRef
  21. Lamming DW, Cummings NE, Rastelli AL, Gao F, Cava E, Bertozzi B, Spelta F, Pili R, Fontana L. Restriction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model. Oncotarget. 2015;6(31):31233-31240. PubMed, PubMedCentral, CrossRef
  22. Cui H, Kong Y, Zhang H.  Oxidative stress, mitochondrial dysfunction, and aging. J Signal Transduct. 2012;2012:646354. PubMed, PubMedCentral, CrossRef
  23. Kudryavtseva AV, Krasnov GS, Dmitriev AA, Alekseev BY, Kardymon OL, Sadritdinova AF, Fedorova MS, Pokrovsky AV, Melnikova NV, Kaprin AD, Moskalev AA, Snezhkina AV. Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget. 2016;7(29):44879-44905. PubMed, PubMedCentral, CrossRef
  24. Brunk UT, Terman A. The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem. 2002;269(8):1996-2002. PubMedCrossRef
  25. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24(5):981-990. PubMed, PubMedCentral, CrossRef
  26. Reeg S, Grune T. Protein Oxidation in Aging: Does It Play a Role in Aging Progression? Antioxid Redox Signal. 2015;23(3):239-255. PubMed, PubMedCentral, CrossRef
  27. Fernando R, Drescher C, Nowotny K, Grune T, Castro JP. Impaired proteostasis during skeletal muscle aging. Free Radic Biol Med. 2019;132:58-66. PubMed, CrossRef
  28. Nowson C, O’Connell S. Protein Requirements and Recommendations for Older People: A Review. Nutrients. 2015;7(8):6874-6899. PubMed, PubMedCentral, CrossRef
  29. Hughes VA, Frontera WR, Roubenoff R, Evans WJ, Singh MA. Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr. 2002;76(2):473-481. PubMed,   CrossRef
  30. Montero-Fernández N, Serra-Rexach JA. Role of exercise on sarcopenia in the elderly. Eur J Phys Rehabil Med. 2013;49(1):131-143. PubMed
  31. Short KR, Nair KS. The effect of age on protein metabolism. Curr Opin Clin Nutr Metab Care. 2000;3(1):39-44. PubMedCrossRef
  32. Strandberg  TE, Pitkälä KH. Frailty in elderly people. Lancet. 2007;369(9570):1328-1329. PubMed, CrossRef
  33. Ozaki A, Uchiyama M, Tagaya H, Ohida T, Ogihara R. The Japanese Centenarian Study: autonomy was associated with health practices as well as physical status. J Am Geriatr Soc. 2007;55(1):95-101. PubMed, CrossRef
  34. Anthony JC, Yoshizaw F, Anthon TG, Vary TC, Jefferson LS, Kimball SR. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J Nutr. 2000;130(10):2413-2419. PubMed, CrossRef
  35. Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab. 2006;291(2):E381-E387. PubMed, CrossRef
  36. Dangin M, Boirie Y, Guillet C, Beaufrère B. Influence of the protein digestion rate on protein turnover in young and elderly subjects. J Nutr. 2002;132(10):3228S-3233S. PubMedCrossRef
  37. Dangin M, Guillet C, Garcia-Rodenas C, Gachon P, Bouteloup-Demange C, Reiffers-Magnani K, Fauquant J, Ballèvre O, Beaufrère B. The rate of protein digestion affects protein gain differently during aging in humans. J Physiol. 2003;549(Pt 2):635-644. PubMed, PubMedCentral, CrossRef
  38. Karelis AD, Messier V, Suppère C, Briand P, Rabasa-Lhoret R. Effect of cysteine-rich whey protein (immunocal®) supplementation in combination with resistance training on muscle strength and lean body mass in non-frail elderly subjects: a randomized, double-blind controlled study. J Nutr Health Aging. 2015;19(5):531-536. PubMed, CrossRef
  39. Grassi M, Petraccia L, Mennuni G, Fontana M, Scarno A, Sabetta S, Fraioli A. Changes, functional disorders, and diseases in the gastrointestinal tract of elderly. Nutr Hosp. 2011;26(4):659-668. PubMed
  40. Wall BT, Hamer HM, de Lange A, Kiskini A, Groen BB, Senden JM, Gijsen AP, Verdijk LB, van Loon LJ. Leucine co-ingestion improves post-prandial muscle protein accretion in elderly men. Clin Nutr. 2013;32(3):412-419. PubMedCrossRef
  41. Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis. Am J Clin Nutr. 2012;96(6):1454-1464. PubMed, CrossRef
  42. Campbell WW, Crim MC, Dallal GE, Young VR, Evans WJ.  Increased protein requirements in elderly people: new data and retrospective reassessments. Am J Clin Nutr. 1994;60(4):501-509. PubMed, CrossRef
  43. Campbell WW, Trappe TA, Wolfe RR, Evans WJ. The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle. J Gerontol A Biol Sci Med Sci. 2001;56(6):M373-M380. PubMed, CrossRef
  44. Courtney-Martin G, Ball RO, Pencharz PB, Elango R. Protein Requirements during Aging. Nutrients. 2016;8(8):492. PubMed, PubMedCentral, CrossRef
  45. Deutz NEP, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-Westphal A, Cederholm T, Cruz-Jentoft A, Krznariç Z, Nair KS, Singer P, Teta D, Tipton K, Calder PC. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr. 2014;33(6):929-936. PubMed, PubMedCentral, CrossRef
  46. Labbadia J, Morimoto RI. The biology of proteostasis in aging and disease. Annu Rev Biochem. 2015;84:435-464. PubMed, PubMedCentral, CrossRef
  47. Klaips CL, Jayaraj GG, Hartl FU. Pathways of cellular proteostasis in aging and disease. J Cell Biol. 2018;217(1):51-63. PubMed, PubMedCentral, CrossRef
  48. Santra M, Dill KA, de Graff AMR. Proteostasis collapse is a driver of cell aging and death. Proc Natl Acad Sci USA. 2019;116(44):22173-22178. PubMed, PubMedCentral, CrossRef
  49. Koga H, Kaushik S, Cuervo AM. Protein homeostasis and aging: The importance of exquisite quality control. Ageing Res Rev. 2011;10(2):205-215. PubMed, PubMedCentral, CrossRef
  50. Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010;22(2):124-131. PubMed, PubMedCentral, CrossRef
  51. Finley D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem. 2009;78:477-513. PubMed, PubMedCentral, CrossRef
  52. Bukau B, Weissman J, Horwich A. Molecular chaperones and protein quality control. Cell. 2006;125(3):443-451. PubMed, CrossRef
  53. Proctor CJ, Soti C, Boys RJ, Gillespi CS, Shanley DP, Wilkinso DJ, Kirkwood TB. Modelling the actions of chaperones and their role in ageing. Mech Ageing Dev. 2005;126(1):119-131. PubMed, CrossRef
  54. Proctor CJ , Lorimer IA. Modelling the role of the Hsp70/Hsp90 system in the maintenance of protein homeostasis. PLoS One. 2011;6(7):e22038. PubMed, PubMedCentral, CrossRef
  55. Friguet B, Bulteau AL, Chondrogianni N, Conconi M, Petropoulos I. Protein degradation by the proteasome and its implications in aging. Ann N Y Acad Sci. 2000;908:143-154. PubMed, CrossRef
  56. Bulteau AL, Petropoulos I, Friguet B. Age-related alterations of proteasome structure and function in aging epidermis. Exp Gerontol. 2000;35(6-7):767-777. PubMed, CrossRef
  57. Terman A, Brunk UT. Oxidative stress, accumulation of biological ‘garbage’, and aging. Antioxid Redox Signal. 2006;8(1-2):197-204. PubMed, CrossRef
  58. Tanaka T, Biancotto A, Moaddel R, Moore AZ, Gonzalez-Freire M, Aon MA, Candia J, Zhang P, Cheung F, Fantoni G, CHI consortium, Semba RD, Luigi Ferrucci L. Plasma proteomic signature of age in healthy humans. Aging Cell. 2018;17(5):e12799. PubMed, PubMedCentral, CrossRef
  59. Fujita Y, Taniguchi Y, Shinkai S, Tanaka M, Ito M. Secreted growth differentiation factor 15 as a potential biomarker for mitochondrial dysfunctions in aging and age-related disorders. Geriatr Gerontol Int. 2016;16(Suppl 1):17-29. PubMed, CrossRef
  60. Chung HK, Ryu D, Kim  KS, Chang JY, Kim YK, Yi HS, Kang SG, Choi MJ, Lee SE, Jung SB, Ryu MJ, Kim SJ, Kweon GR, Kim H, Hwang JH, Lee CH, Lee SJ, Wall CE, Downes M, Evans RM , Auwerx J, Shong M. Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis. J Cell Biol. 2017;216(1):149-165. PubMed, PubMedCentral, CrossRef
  61. Smith CD, Carney JM, Starke-Reed PE, Oliver CN, Stadtman ER, Floyd RA, Markesbery WR. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci USA. 1991;88(23):10540-10543.  PubMed, PubMedCentral, CrossRef
  62. Basisty N, Meyer JG, Schilling B. Protein Turnover in Aging and Longevity. Proteomics. 2018;18(5-6):e1700108. PubMed, PubMedCentral, CrossRef
  63. Yang L, Licastro D, Cava E, Veronese N, Spelta F, Rizza W, Bertozzi B, Villareal DT, Hotamisligil GS, Holloszy JO, Fontana L. Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle. Cell Rep. 2016;14(3):422-428. PubMed, CrossRef
  64. Weichhart T. mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review. Gerontology. 2018;64(2):127-134. PubMed, PubMedCentral, CrossRef
  65. Soultoukis GA, Partridge L. Dietary Protein, Metabolism, and Aging. Annu Rev Biochem. 2016;85:5-34. PubMed, CrossRef
  66. Arbor S. Where and how in the mTOR pathway inhibitors fight ageing: Rapamycin, resveratrol, and metformin. from:  Resveratrol – adding life to years, not adding years to life. Intech Open. 2019:93-101. CrossRef
  67. Xie QB, Liang Y, Yang M, Yang Y, Cen XM, Yin G. DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture. J Immunol Res. 2017;2017:5252840. PubMed, PubMedCentral, CrossRef
  68. Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015;161(1):106-118. PubMed, PubMedCentral, CrossRef
  69. Edwards C, Canfield J, Copes N, Brito A, Rehan M, Lipps D, Brunquell J, Westerheide SD, Bradshaw PC. Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans. BMC Genet. 2015;16(1):8. PubMed, PubMedCentral, CrossRef
  70. Santos J, Leão C, Sousa MJ. Growth culture conditions and nutrient signaling modulating yeast chronological longevity. Oxid Med Cell Longev. 2012;2012:680304. PubMed, PubMedCentral, CrossRef
  71. Kołodziej U, Maciejczyk M, Niklińska W, Waszkiel D, Żendzian-Piotrowska M, Żukowski P, Zalewska A. Chronic high-protein diet induces oxidative stress and alters the salivary gland function in rats. Arch Oral Biol. 2017;84:6-12. PubMed, CrossRef
  72. Ayala V, Naudí A, Sanz A, Caro P, Portero-Otin M, Barja G, Pamplona R. Dietary protein restriction decreases oxidative protein damage, peroxidizability index, and mitochondrial complex I content in rat liver. J Gerontol A Biol Sci Med Sci. 2007;62(4):352-360. PubMed, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.