CoChat
Sign Up
Cited by 527Autophagy in Disease and TherapyGenetics, Aging, and Longevity in Model OrganismsUbiquitin and proteasome pathways

Autophagy and aging: keeping that old broom working

Open access
Cuervo, Ana Maria·2008·Trends in Genetics
DOI 10.1016/j.tig.2008.10.002PMC PMC2745226
Open this paper in CoChat — free account

Abstract

Autophagy, a highly conserved mechanism of quality control inside cells, is essential for the maintenance of cellular homeostasis and for the orchestration of an efficient cellular response to stress. The decrease in autophagic activity observed in almost all cells and tissues as organisms age was proposed to contribute to different aspects of the aging phenotype and to the aggravation of detrimental age-related diseases. The recent advances in our understanding of the molecular mechanisms underlying autophagy and the identification of the subset of genes involved in this process has enabled the use of genetic manipulations to start testing this hypothesis. Here, I review the recent genetic evidence in support of tight connections between autophagy, health span and aging.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.tig.2008.10.002

Cites

9 of 9 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 62

  1. [1]Morimoto RI Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging Genes Dev 2008 22 1427 1438 18519635 PMC2732416
  2. [2]Goldberg AL Protein degradation and protection against misfolded or damaged proteins Nature 2003 426 895 899 14685250
  3. [3]Feldman DE Frydman J Protein folding in vivo: the importance of molecular chaperones Curr. Opin. Struct. Biol 2000 10 26 33 10679467
  4. [4]Ciechanover A Proteolysis: from the lysosome to ubiquitin and the proteasome Nat. Rev. Mol. Cell Biol 2005 6 79 87 15688069
  5. [5]Finkbeiner S Disease-modifying pathways in neurodegeneration J. Neurosci 2006 26 10349 10357 17035516 PMC6674695
  6. [6]Ward WF Protein degradation in the aging organism Prog. Mol. Subcell. Biol 2002 29 35 42 11908071
  7. [7]Martinez-Vicente M Protein degradation and aging Exp. Gerontol 2005 40 622 633 16125351
  8. [8]Mizushima N Autophagy fights disease through cellular self-digestion Nature 2008 451 1069 1075 18305538 PMC2670399
  9. [10]Klionsky DJ A unified nomenclature for yeast autophagy-related genes Dev. Cell 2003 5 539 545 14536056
  10. [11]Yorimitsu T Klionsky DJ Autophagy: molecular machinery for self-eating Cell Death Differ 2005 12 1542 1552 16247502 PMC1828868
  11. [12]Shintani T Klionsky D Autophagy in health and disease: a double-edged sword Science 2004 306 990 995 15528435 PMC1705980
  12. [13]Massey AC Chaperone-mediated autophagy in aging and disease Curr. Top. Dev. Biol 2006 73 205 235 16782460
  13. [14]Cuervo AM Autophagy: in sickness and in health Trends Cell Biol 2004 14 70 77 15102438
  14. [15]Mizushima N Klionsky D Protein turnover via autophagy: implications for metabolism Annu. Rev. Nutr 2007 27 19 40 17311494
  15. [16]Levine B Deretic V Unveiling the roles of autophagy in innate and adaptive immunity Nat. Rev. Immunol 2007 7 767 777 17767194 PMC7097190
  16. [17]Cuervo AM Autophagy: many pathways to the same end Mol. Cell. Biochem 2004 263 55 72 27520665
  17. [19]Hara T Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice Nature 2006 441 885 889 16625204
  18. [21]Komatsu M Loss of autophagy in the central nervous system causes neurodegeneration in mice Nature 2006 441 880 884 16625205
  19. [22]Nakai A The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress Nat. Med 2007 13 619 624 17450150
  20. [23]Klionsky DJ How shall I eat thee? Autophagy 2007 3 413 416 17568180
  21. [24]Marzella L Autophagy, heterophagy, microautophagy and crinophagy as the means for intracellular degradation Virchows Arch. B Cell Pathol. Incl. Mol. Pathol 1981 36 219 234 6116336
  22. [25]Dice JF Chaperone-mediated autophagy Autophagy 2007 3 295 299 17404494
  23. [27]Stroikin Y Testing the ‘garbage’ accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy Biogerontology 2005 6 39 47 15834662
  24. [28]Navratil M Giant mitochondria do not fuse and exchange their contents with normal mitochondria Exp. Cell Res 2008 314 164 172 17964571
  25. [29]Vittorini S The age-related accumulation of protein carbonyl in rat liver correlates with the age-related decline in liver proteolytic activities J. Gerontol. A Biol. Sci. Med Sci 1999 54 B318 B323 10496537
  26. [30]Terman A The effect of age on formation and elimination of autophagic vacuoles in mouse hepatocytes Gerontology 1995 41 319 325 8821342
  27. [31]Brunk UT Terman A Lipofuscin: mechanisms of age-related accumulation and influence on cell function Free Radic. Biol. Med 2002 33 611 619 12208347
  28. [32]Donati A Age-related changes in the regulation of autophagic proteolysis in rat isolated hepatocytes J. Gerontol. A Biol. Sci. Med. Sci 2001 56 B288 B293 11445593
  29. [33]Donati A Effect of aging and anti-aging caloric restriction on the endocrine regulation of rat liver autophagy J. Gerontol. A Biol. Sci. Med. Sci 2008 63 550 555 18559627
  30. [34]Droge W Kinscherf R Aberrant insulin receptor signaling and amino acid homeostasis as a major cause of oxidative stress in aging Antioxid. Redox Signal 2008 10 661 678 18162053
  31. [35]Meijer AJ Codogno P Macroautophagy: protector in the diabetes drama? Autophagy 2007 3 523 526 17534140
  32. [36]Cavallini G The protection of rat liver autophagic proteolysis from the age-related decline co-varies with the duration of anti-ageing food restriction Exp. Gerontol 2001 36 497 506 11250121
  33. [37]Lane MA Caloric restriction mimetics: a novel approach for biogerontology Methods Mol. Biol 2007 371 143 149 17634579
  34. [38]Masoro EJ Caloric restriction and aging: controversial issues J. Gerontol. A Biol. Sci. Med. Sci 2006 61 14 19 16456190
  35. [39]Okada AA Dice JF Altered degradation of intracellular proteins in aging human fibroblasts Mech. Ageing Dev 1984 26 341 356 6482527
  36. [40]Cuervo AM Dice JF Age-related decline in chaperone-mediated autophagy J. Biol. Chem 2000 275 31505 31513 10806201
  37. [41]Reznick AZ Gershon D The effect of age on the protein degradation system in the nematode Turbatrix aceti Mech. Ageing Dev 1979 11 403 415 529841
  38. [42]Johnson TE Caenorhabditis elegans 2007: the premier model for the study of aging Exp. Gerontol 2008 43 1 4 17977684 PMC2219387
  39. [43]Melendez A Autophagy genes are essential for dauer development and life-span extension in C. elegans Science 2003 301 1387 1391 12958363
  40. [44]Hars ES Autophagy regulates ageing in C. elegans Autophagy 2007 3 93 95 17204841
  41. [45]Hansen M A role for autophagy in the extension of lifespan by dietary restriction in C. elegans PLoS Genet 2008 4 e24 18282106 PMC2242811
  42. [46]Tavernarakis N The effects of p53 on whole organism longevity are mediated by autophagy Autophagy 2008 4 870 873 18728385
  43. [48]Salih DA Brunet A FoxO transcription factors in the maintenance of cellular homeostasis during aging Curr. Opin. Cell Biol 2008 20 126 136 18394876 PMC2387118
  44. [49]Tóth ML Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans Autophagy 2008 4 330 338 18219227
  45. [51]Simonsen A Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila Autophagy 2008 4 176 184 18059160
  46. [52]Mörck C Pilon M C. elegans feeding defective mutants have shorter body lengths and increased autophagy BMC Dev. Biol 2006 6 39 16884547 PMC1559592
  47. [53]Kaeberlein M Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients Science 2005 310 1193 1196 16293764
  48. [54]Sarbassov DD Growing roles for the mTOR pathway Curr. Opin. Cell Biol 2005 17 596 603 16226444
  49. [56]Juhasz G Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila Genes Dev 2007 21 3061 3066 18056421 PMC2081972
  50. [57]Massey AC Consequences of the selective blockage of chaperone-mediated autophagy Proc. Natl. Acad. Sci. U. S. A 2006 103 5905 5910 16585521 PMC1458654
  51. [58]Martinez-Vicente M Cuervo AM Autophagy and neurodegeneration: when the cleaning crew goes on strike Lancet Neurol 2007 6 352 361 17362839
  52. [59]Jin S Autophagy, mitochondrial quality control, and oncogenesis Autophagy 2006 2 80 84 16874075
  53. [60]Lemasters JJ Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging Rejuvenation Res 2005 8 3 5 15798367
  54. [62]Donati A In vivo effect of an antilipolytic drug (3,5′-dimethylpyrazole) on autophagic proteolysis and autophagy-related gene expression in rat liver Biochem. Biophys. Res. Commun 2008 366 786 792 18082617
  55. [63]Marino G Premature aging in mice activates a systemic metabolic response involving autophagy induction Hum. Mol. Genet 2008 17 2196 2211 18443001
  56. [64]Wohlgemuth SE Autophagy in the heart and liver during normal aging and calorie restriction Rejuvenation Res 2007 10 281 292 17665967
  57. [65]Shibata M Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1 J. Biol. Chem 2006 281 14474 14485 16522639
  58. [66]Zhang C Cuervo AM Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function Nat. Med 2008 14 959 965 18690243 PMC2722716
  59. [67]Shiozaki M Morphological and biochemical signs of age-related neurodegenerative changes in klotho mutant mice Neuroscience 2008 152 924 941 18343589
  60. [68]Tsukada M Ohsumi M Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae FEBS Lett 1993 333 169 174 8224160
  61. [69]Thumm M Isolation of autophagocytosis mutants of Saccharomyces cerevisiae FEBS Lett 1994 349 275 280 8050581
  62. [70]Harding TM Isolation and characterization of yeast mutants in the cytoplasm to vacuoles protein targeting pathway J. Cell Biol 1995 131 591 602 7593182 PMC2120622

Cited by

Sorted by citations

Authors
Cuervo, A. M.
Venue
Trends in Genetics
Publisher
Elsevier BV
Published
2008-12
Volume
24
Issue
12
Pages
604-612
ISSN
0168-9525 (ISSN-L)
DOI
10.1016/j.tig.2008.10.002
PMC
PMC2745226
OpenAlex
W2140664473
Cited by
527
References
9
Citations by year
2026: 8 · 2025: 13 · 2024: 12 · 2023: 14 · 2022: 23 · 2021: 34 · 2020: 27 · 2019: 34 · 2018: 38 · 2017: 40 · 2016: 44 · 2015: 37 · 2014: 42 · 2013: 37 · 2012: 28
FWCI
3.43
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Trends in Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (R03AG019834, R01AG021904, R37AG021904, P01AG031782, AG-021904, AG031782, R21AG025355)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK041918, P01DK041918)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
autophagy, aging, healthspan, age-related diseases, cellular homeostasis, stress response, genetic engineering, autophagy-related genes, cell quality control
MeSH terms
Aging, Animals, Autophagy, Humans, Longevity

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review