Skip to main content
SpringerLink
Log in

Ribosome, Protein Synthesis, and Aging

  • Chapter
  • First Online:
Models, Molecules and Mechanisms in Biogerontology

Abstract

Aging involves a steady decline in the organism’s fitness leading to disease and death. Loss of proteostasis and genomic instability are considered to be some of the hallmarks of aging. The molecular aging of proteins due to chemical changes and damage to the polypeptide chains contributes to loss of proteostasis, while dysregulation of the transcriptional surveillance mechanisms leads to genomic instability. Emerging evidence points to a causative relationship between the regulation of protein synthesis and aging. This chapter attempts to summarize the involvement of various components of the translation machinery in the aging process and how they in turn get reciprocally affected by it. The roles played by the ribosome, transcriptional and translational regulation, and the signaling pathways regulating these processes during aging have been discussed. Also, theories suggesting the correlation between downregulation of protein synthesis and its contribution to longevity have been explained.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–217.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Charmpilas N, Daskalaki I, Papandreou ME, Tavernarakis N. Protein synthesis as an integral quality control mechanism during ageing. Ageing Res Rev. 2015;23(Pt A):75–89.

    Article  CAS  PubMed  Google Scholar 

  3. Gonskikh Y, Polacek N. Alterations of the translation apparatus during aging and stress response. Mech Ageing Dev. 2017;168:30–6.

    Article  CAS  PubMed  Google Scholar 

  4. Karamyshev AL, Patrick AE, Karamysheva ZN, Griesemer DS, Hudson H, Tjon-Kon-Sang S, et al. Inefficient SRP interaction with a nascent chain triggers a mRNA quality control pathway. Cell. 2014;156(1–2):146–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kirstein-Miles J, Scior A, Deuerling E, Morimoto RI. The nascent polypeptide-associated complex is a key regulator of proteostasis. EMBO J. 2013;32(10):1451–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Liu B, Han Y, Qian S-B. Cotranslational response to proteotoxic stress by elongation pausing of ribosomes. Mol Cell. 2013;49(3):453–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Essers PB, Nonnekens J, Goos YJ, Betist MC, Viester MD, Mossink B, et al. A long noncoding RNA on the ribosome is required for lifespan extension. Cell Rep. 2015;10:339–45.

    Article  CAS  PubMed  Google Scholar 

  8. Chen D, Pan KZ, Palter JE, Kapahi P. Longevity determined by developmental arrest genes in Caenorhabditis elegans. Aging Cell. 2007;6(4):525–33.

    Article  CAS  PubMed  Google Scholar 

  9. Steffen KK, MacKay VL, Kerr EO, Tsuchiya M, Hu D, Fox LA, et al. Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4. Cell. 2008;133(2):292–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Schosserer M, Minois N, Angerer TB, Amring M, Dellago H, Harreither E, et al. Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nat Commun. 2015;6:6158.

    Article  CAS  PubMed  Google Scholar 

  11. Xue S, Barna M. Specialized ribosomes: a new frontier in gene regulation and organismal biology. Nat Rev Mol Cell Biol. 2012;13(6):355–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vesper O, Amitai S, Belitsky M, Byrgazov K, Kaberdina AC, Engelberg-Kulka H, et al. Selective translation of leaderless mRNAs by specialized ribosomes generated by MazF in Escherichia coli. Cell. 2011;147(1):147–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Glass D, Viñuela A, Davies MN, Ramasamy A, Parts L, Knowles D, et al. Gene expression changes with age in skin, adipose tissue, blood and brain. Genome Biol. 2013;14(7):R75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. McCarroll SA, Murphy CT, Zou S, Pletcher SD, Chin C-S, Jan YN, et al. Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nat Genet. 2004;36(2):197–204.

    Article  CAS  PubMed  Google Scholar 

  15. Zahn JM, Sonu R, Vogel H, Crane E, Mazan-Mamczarz K, Rabkin R, et al. Transcriptional profiling of aging in human muscle reveals a common aging signature. PLoS Genet. 2006;2(7):e115.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Zahn JM, Poosala S, Owen AB, Ingram DK, Lustig A, Carter A, et al. AGEMAP: a gene expression database for aging in mice. PLoS Genet. 2007;3(11):e201.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Lund J, Tedesco P, Duke K, Wang J, Kim SK, Johnson TE. Transcriptional profile of aging in C. elegans. Curr Biol. 2002;12(18):1566–73.

    Article  CAS  PubMed  Google Scholar 

  18. Van Driessche N, Shaw C, Katoh M, Morio T, Sucgang R, Ibarra M, et al. A transcriptional profile of multicellular development in Dictyostelium discoideum. Development. 2002;129(7):1543–52.

    Article  PubMed  Google Scholar 

  19. Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, Yang L, et al. The developmental transcriptome of Drosophila melanogaster. Nature. 2011;471(7339):473–9.

    Article  CAS  PubMed  Google Scholar 

  20. Zhan M, Yamaza H, Sun Y, Sinclair J, Li H, Zou S. Temporal and spatial transcriptional profiles of aging in Drosophila melanogaster. Genome Res. 2007;17(8):1236–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kumar A, Gibbs JR, Beilina A, Dillman A, Kumaran R, Trabzuni D, et al. Age-associated changes in gene expression in human brain and isolated neurons. Neurobiol Aging. 2013;34(4):1199–209.

    Article  CAS  PubMed  Google Scholar 

  22. Yang J, Huang T, Petralia F, Long Q, Zhang B, Argmann C, et al. Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases. Sci Rep. 2015;5:15145.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Zierer J, Pallister T, Tsai P-C, Krumsiek J, Bell JT, Lauc G, et al. Exploring the molecular basis of age-related disease comorbidities using a multi-omics graphical model. Sci Rep. 2016. 5;6:37646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Geigl JB, Langer S, Barwisch S, Pfleghaar K, Lederer G, Speicher MR. Analysis of gene expression patterns and chromosomal changes associated with aging. Cancer Res. 2004;64(23):8550–7.

    Article  CAS  PubMed  Google Scholar 

  25. Somel M, Khaitovich P, Bahn S, Pääbo S, Lachmann M. Gene expression becomes heterogeneous with age. Curr Biol. 2006;16(10):R359–60.

    Article  CAS  PubMed  Google Scholar 

  26. Bahar R, Hartmann CH, Rodriguez KA, Denny AD, Busuttil RA, Dollé MET, et al. Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature. 2006;441(7096):1011–4.

    Article  CAS  PubMed  Google Scholar 

  27. Carlson KA, Gardner K, Pashaj A, Carlson DJ, Yu F, Eudy JD, et al. Genome-wide gene expression in relation to age in large laboratory cohorts of drosophila melanogaster. Genet Res Int. 2015;2015:1–19.

    Article  Google Scholar 

  28. Viñuela A, Snoek LB, Riksen JAG, Kammenga JE. Genome-wide gene expression regulation as a function of genotype and age in C. elegans. Genome Res. 2010 Jul;20(7):929–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Chen G, Lustig A, Weng N. T cell aging: a review of the transcriptional changes determined from genome-wide analysis. Front Immunol. [Internet]. 2013 [cited 2018 July 6];4. Available from: http://journal.frontiersin.org/article/10.3389/fimmu.2013.00121/abstract

  30. Enge M, Arda HE, Mignardi M, Beausang J, Bottino R, Kim SK et al. Single cell transcriptome analysis of human pancreas reveals transcriptional signatures of aging and somatic mutation patterns. 2017 [cited 2018 July 6]. Available from: http://biorxiv.org/lookup/doi/10.1101/108043

  31. Benayoun BA, Pollina EA, Brunet A. Epigenetic regulation of ageing: linking environmental inputs to genomic stability. Nat Rev Mol Cell Biol. 2015;16(10):593–610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Masuda K, Kuwano Y, Nishida K, Rokutan K. General RBP expression in human tissues as a function of age. Ageing Res Rev. 2012;11(4):423–31.

    Article  CAS  PubMed  Google Scholar 

  33. Borbolis F, Syntichaki P. Cytoplasmic mRNA turnover and ageing. Mech Ageing Dev. 2015;152:32–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pal M, Ishigaki Y, Nagy E, Maquat LE. Evidence that phosphorylation of human Upfl protein varies with intracellular location and is mediated by a wortmannin-sensitive and rapamycin-sensitive PI 3-kinase-related kinase signaling pathway. RNA. 2001;7(1):5–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Miller MA, Olivas WM. Roles of Puf proteins in mRNA degradation and translation. Wiley Interdiscip Rev RNA. 2011;2(4):471–92.

    Article  CAS  PubMed  Google Scholar 

  36. Wei Y-N, Hu H-Y, Xie G-C, Fu N, Ning Z-B, Zeng R et al. Transcript and protein expression decoupling reveals RNA binding proteins and miRNAs as potential modulators of human aging. Genome Biol [Internet]. 2015 [cited 2018 July 6];16(1). Available from: http://genomebiology.com/2015/16/1/41

  37. Bakheet T, Williams BRG, Khabar KSA. ARED 3.0: the large and diverse AU-rich transcriptome. Nucleic Acids Res. 2006;34(Database issue):D111–4.

    Article  CAS  PubMed  Google Scholar 

  38. von Roretz C, Di Marco S, Mazroui R, Gallouzi I-E. Turnover of AU-rich-containing mRNAs during stress: a matter of survival. Wiley Interdiscip Rev RNA. 2011;2(3):336–47.

    Article  CAS  Google Scholar 

  39. Pont AR, Sadri N, Hsiao SJ, Smith S, Schneider RJ. mRNA decay factor AUF1 maintains normal aging, telomere maintenance, and suppression of senescence by activation of telomerase transcription. Mol Cell. 2012;47(1):5–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Abe M, Naqvi A, Hendriks G-J, Feltzin V, Zhu Y, Grigoriev A, et al. Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila. Genes Dev. 2014;28(1):44–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Boehm M. A developmental timing microRNA and its target regulate life span in C. elegans. Science. 2005;310(5756):1954–7.

    Article  CAS  PubMed  Google Scholar 

  42. Shen Y, Wollam J, Magner D, Karalay O, Antebi A. A steroid receptor-microRNA switch regulates life span in response to signals from the gonad. Science. 2012;338(6113):1472–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Pincus Z, Smith-Vikos T, Slack FJ. MicroRNA predictors of longevity in Caenorhabditis elegans. Kim SK, editor. PLoS Genet. 2011;7(9):e1002306.

    Google Scholar 

  44. Garg D, Cohen SM. miRNAs and aging: a genetic perspective. Ageing Res Rev. 2014;17:3–8.

    Article  CAS  PubMed  Google Scholar 

  45. Jung HJ, Suh Y. MicroRNA in aging: from discovery to biology. Curr Genomics. 2012;13(7):548–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Harries LW. MicroRNAs as mediators of the ageing process. Genes (Basel). 2014;5(3):656–70.

    Article  CAS  Google Scholar 

  47. Grammatikakis I, Panda AC, Abdelmohsen K, Gorospe M. Long noncoding RNAs(lncRNAs) and the molecular hallmarks of aging. Aging (Albany NY). 2014;6(12):992–1009.

    Article  Google Scholar 

  48. Kour S, Rath PC. Long noncoding RNAs in aging and age-related diseases. Ageing Res Rev. 2016;26:1–21.

    Article  CAS  PubMed  Google Scholar 

  49. Kim J, Kim KM, Noh JH, Yoon J-H, Abdelmohsen K, Gorospe M. Long noncoding RNAs in diseases of aging. Biochimica et Biophysica Acta (BBA) Gene Regul Mech. 2016;1859(1):209–21.

    Article  CAS  Google Scholar 

  50. Tavernarakis N. Ageing and the regulation of protein synthesis: a balancing act? Trends Cell Biol. 2008;18(5):228–35.

    Article  CAS  PubMed  Google Scholar 

  51. Rajesh K, Papadakis AI, Kazimierczak U, Peidis P, Wang S, Ferbeyre G, et al. eIF2α phosphorylation bypasses premature senescence caused by oxidative stress and pro-oxidant antitumor therapies. Aging. 2013;5(12):884–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Pan KZ, Palter JE, Rogers AN, Olsen A, Chen D, Lithgow GJ, et al. Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell. 2007;6(1):111–9.

    Article  CAS  PubMed  Google Scholar 

  53. Rogers AN, Chen D, McColl G, Czerwieniec G, Felkey K, Gibson BW, et al. Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. Cell Metab. 2011;14(1):55–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Syntichaki P, Troulinaki K, Tavernarakis N. eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature. 2007;445(7130):922–6.

    Article  CAS  PubMed  Google Scholar 

  55. Hansen M, Taubert S, Crawford D, Libina N, Lee S-J, Kenyon C. Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell. 2007;6(1):95–110.

    Article  CAS  PubMed  Google Scholar 

  56. Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, et al. 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in drosophila. Cell. 2009;139(1):149–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tavernarakis N. Protein synthesis and aging: eIF4E and the soma vs. germline distinction. Cell Cycle. 2007;6(10):1168–71.

    Article  CAS  PubMed  Google Scholar 

  58. Muñoz MF, Argüelles S, Cano M, Marotta F, Ayala A. Aging and oxidative stress decrease pineal elongation factor 2: in vivo protective effect of melatonin in young rats treated with Cumene Hydroperoxide: P INEAL eEF-2 P ROTECTION BY M ELATONIN. J Cell Biochem. 2017;118(1):182–90.

    Article  PubMed  CAS  Google Scholar 

  59. Conn CS, Qian S-B. Nutrient signaling in protein homeostasis: an increase in quantity at the expense of quality. Sci Signal. 2013;6(271):ra24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Chiabudini M, Tais A, Zhang Y, Hayashi S, Wölfle T, Fitzke E, et al. Release factor eRF3 mediates premature translation termination on polylysine-stalled ribosomes in Saccharomyces cerevisiae. Mol Cell Biol. 2014;34(21):4062–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Shcherbik N, Chernova TA, Chernoff YO, Pestov DG. Distinct types of translation termination generate substrates for ribosome-associated quality control. Nucleic Acids Res. 2016;44(14):6840–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Simm A. Protein glycation during aging and in cardiovascular disease. J Proteome. 2013;92:248–59.

    Article  CAS  Google Scholar 

  63. Tanase M, Urbanska AM, Zolla V, Clement CC, Huang L, Morozova K, et al. Role of carbonyl modifications on aging-associated protein aggregation. Sci Rep. 2016;6:19311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Höhn A, König J, Grune T. Protein oxidation in aging and the removal of oxidized proteins. J Proteome. 2013;92:132–59.

    Article  CAS  Google Scholar 

  65. Gorisse L, Pietrement C, Vuiblet V, Schmelzer CEH, Köhler M, Duca L, et al. Protein carbamylation is a hallmark of aging. Proc Natl Acad Sci U S A. 2016;113(5):1191–6.

    Article  CAS  PubMed  Google Scholar 

  66. Jaisson S, Gillery P. Evaluation of nonenzymatic posttranslational modification-derived products as biomarkers of molecular aging of proteins. Clin Chem. 2010;56(9):1401–12.

    Article  PubMed  Google Scholar 

  67. Mirzaei H, Suarez JA, Longo VD. Protein and amino acid restriction, aging and disease: from yeast to humans. Trends Endocrinol Metab. 2014;25(11):558–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Stout GJ, Stigter ECA, Essers PB, Mulder KW, Kolkman A, Snijders DS, et al. Insulin/IGF-1-mediated longevity is marked by reduced protein metabolism. Mol Syst Biol. 2014;9(1):679.

    Article  CAS  Google Scholar 

  69. Walther DM, Kasturi P, Zheng M, Pinkert S, Vecchi G, Ciryam P, et al. Widespread proteome remodeling and aggregation in aging C. elegans. Cell. 2015;161(4):919–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Höhn A, Weber D, Jung T, Ott C, Hugo M, Kochlik B, et al. Happily (n)ever after: aging in the context of oxidative stress, proteostasis loss and cellular senescence. Redox Biol. 2017;11:482–501.

    Article  PubMed  CAS  Google Scholar 

  71. Vernace VA, Arnaud L, Schmidt-Glenewinkel T, Figueiredo-Pereira ME. Aging perturbs 26S proteasome assembly in Drosophila melanogaster. FASEB J. 2007 Sep;21(11):2672–82.

    Article  CAS  PubMed  Google Scholar 

  72. Ghazi A, Henis-Korenblit S, Kenyon C. Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 2007;104(14):5947–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Chondrogianni N, Voutetakis K, Kapetanou M, Delitsikou V, Papaevgeniou N, Sakellari M, et al. Proteasome activation: an innovative promising approach for delaying aging and retarding age-related diseases. Ageing Res Rev. 2015;23:37–55.

    Article  CAS  PubMed  Google Scholar 

  74. Harris H, Rubinsztein DC. Control of autophagy as a therapy for neurodegenerative disease. Nat Rev Neurol. 2011;8(2):108–17.

    Article  PubMed  CAS  Google Scholar 

  75. Johnson JE, Johnson FB. Methionine restriction activates the retrograde response and confers both stress tolerance and lifespan extension to yeast, mouse and human cells. PLoS One. 2014;9(5):e97729.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Rattan SIS. Hormesis in aging. Ageing Res Rev. 2008 Jan;7(1):63–78.

    Article  PubMed  Google Scholar 

  77. F a C W, de S a H P, Boers-Trilles VE, AMA S. Hormesis and cellular quality control: a possible explanation for the molecular mechanisms that underlie the benefits of mild stress. Dose Response. 2012;11(3):413–30.

    Google Scholar 

  78. Hipkiss AR. Accumulation of altered proteins and ageing: causes and effects. Exp Gerontol. 2006;41(5):464–73.

    Article  CAS  PubMed  Google Scholar 

  79. Hipkiss AR. On why decreasing protein synthesis can increase lifespan. Mech Ageing Dev. 2007;128(5–6):412–4.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India

    Reetika Manhas & Pramod C. Rath

Authors
  1. Reetika Manhas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pramod C. Rath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Reetika Manhas or Pramod C. Rath .

Editor information

Editors and Affiliations

  1. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India

    Pramod C. Rath

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Manhas, R., Rath, P.C. (2020). Ribosome, Protein Synthesis, and Aging. In: Rath, P. (eds) Models, Molecules and Mechanisms in Biogerontology. Springer, Singapore. https://doi.org/10.1007/978-981-32-9005-1_4

Download citation

Publish with us

Policies and ethics

Search

Navigation