Abstract
The microscopic worm Caenorhabditis elegans (C. elegans) is one of the most prominent animal models for aging studies. This is underscored by the fact that most of the genes and interventions that modulate the aging process, such as the insulin/IGF pathway, caloric restriction and mitochondrial signalling, were first identified in this organism. Remarkably, many features of the mammalian aging process are recapitulated in C. elegans: over time, damage to macromolecule accumulates, structural cellular components progressively deteriorate, physiological functions decline, resistance to stress and infections decreases, while morbidity and mortality rates increase. In humans, age represents risk factor number one for most diseases ultimately leading to death in industrialized countries, namely cardiovascular diseases, cancer and neurodegenerative disorders. Genes regulating aging in C. elegans are evolutionarily conserved and their deregulation is often involved in the development of age-associated diseases in humans. It is therefore likely that any intervention that extends C. elegans lifespan will indicate strategies to positively impact on healthy human longevity.
Zusammenfassung
Der mikroskopisch kleine Wurm Caenorhabditis elegans (C. elegans) ist eines der bedeutendsten Tiermodelle für Alternsstudien. Dies wird dadurch unterstrichen, dass die meisten Gene und Interventionen, die den Alternsprozess modulieren, wie der Insulin-IGF-Signalweg, kalorische Restriktion und mitochondriale Signale, zuerst in diesem Organismus identifiziert wurden. Bemerkenswerterweise kommen viele Merkmale der Säugeralterung bei C. elegans vor: Akkumulation geschädigter Makromoleküle, progressiver Zerfall struktureller Zellkomponenten, Nachlassen physiologischer Funktionen, Abnahme von Stress- und Infektionsresistenz, Zunahme von Morbidität und Mortalität. Beim Mensch ist Altern der Hauptrisikofaktor für die meisten letztlich zum Tod führenden Krankheiten, wie kardiovaskuläre und neurodegenerative Erkrankungen oder Krebs. Gene, die den Alternsprozess in C. elegans regulieren, sind evolutionär konserviert, und ihre Deregulation ist häufig an der Entstehung alternsassoziierter Krankheiten beteiligt. Daher ist anzunehmen, dass Interventionen, die die Lebensspanne bei C. elegans verlängern, Ansätze für Strategien zur Verlängerung der gesunden Lebensspanne beim Menschen liefern werden.
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References
Fontana L, Partridge L, Longo VD (2010) Extending healthy life span—from yeast to humans. Science 328:321–326
Kenyon CJ (2010) The genetics of ageing. Nature 464:504–512
Christensen K, Johnson TE, Vaupel JW (2006) The quest for genetic determinants of human longevity: challenges and insights. Nat Rev Genet 7:436–448
Kaeberlein M (2013) Longevity and aging. F1000Prime Rep 5:5
Johnson TE (2013) 25 Years after age-1: genes, interventions and the revolution in aging research. Exp gerontol 48:640–643
Klass MR (1983) A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results. Mech Ageing Dev 22:279–286
Friedman DB, Johnson TE (1988) Three mutants that extend both mean and maximum life span of the nematode, Caenorhabditis elegans, define the age-1 gene. J Gerontol 43:B102–B109
Yanos ME, Bennett CF, Kaeberlein M (2012) Genome-wide RNAi longevity screens in Caenorhabditis elegans. Curr Genomics 13:508–518
Antebi A (2007) Genetics of aging in Caenorhabditis elegans. PLoS Genet 3:1565–1571
Kenyon C et al (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366(6454):461–464
Li W, Kennedy SG, Ruvkun G (2003) daf-28 Encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway. Genes Dev 17:844–858
Tissenbaum HA (2012) Genetics, life span, health span, and the aging process in Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci 67:503–510
Lapierre LR, Hansen M (2012) Lessons from C. elegans: signaling pathways for longevity. Trends Endocrinol Metab 23:637–644
Florez-McClure ML et al (2007) Decreased insulin-receptor signaling promotes the autophagic degradation of beta-amyloid peptide in C. elegans. Autophagy 3:569–580
Pinkston JM et al (2006) Mutations that increase the life span of C. elegans inhibit tumor growth. Science 313:971–975
Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300
Gems D, Partridge L (2013) Genetics of longevity in model organisms: debates and paradigm shifts. Annu Rev Physiol 75:621–644
Hekimi S, Lapointe J, Wen Y (2011) Taking a “good” look at free radicals in the aging process. Trends Cell Biol 21:569–576
Ventura N, Rea SL, Testi R (2006) Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial-associated diseases. Exp Gerontol 41:974–991
Dillin A et al (2002) Rates of behavior and aging specified by mitochondrial function during development. Science 298:2398–2401
Rea SL, Ventura N, Johnson TE (2007) Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biol 5:e259
Ventura N, Rea SL (2007) Caenorhabditis elegans mitochondrial mutants as an investigative tool to study human neurodegenerative diseases associated with mitochondrial dysfunction. Biotechnol J 2:584–595
Schiavi A et al (2013) Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. Exp Gerontol 48:191–201
Butler JA et al (2013) A metabolic signature for long life in the Caenorhabditis elegans Mit mutants. Aging Cell 12:130–138
Butler JA et al (2010) Long-lived mitochondrial (Mit) mutants of Caenorhabditis elegans utilize a novel metabolism. FASEB J 24:4977–4988
Ventura N et al (2009) p53/CEP-1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress. Aging Cell 8:380–393
Torgovnick A et al (2010) A role for p53 in mitochondrial stress response control of longevity in C. elegans. Exp Gerontol 45:550–557
Lee SJ, Hwang AB, Kenyon C (2010) Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20:2131–2136
Walter L et al (2011) The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans. PLoS Biol 9:e1001084
Nargund AM et al (2012) Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 337:587–590
Haynes CM, Fiorese CJ, Lin YF (2013) Evaluating and responding to mitochondrial dysfunction: the mitochondrial unfolded-protein response and beyond. Trends Cell Biol 23:311–318
Jeong DE et al (2012) Regulation of lifespan by chemosensory and thermosensory systems: findings in invertebrates and their implications in mammalian aging. Front Genet 3:218
Hubbard EJ, Greenstein D (2005) Introduction to the germ line. WormBook 1:1–4
Antebi A (2012) Regulation of longevity by the reproductive system. Exp Gerontol 48:596–602
White JG et al (1986) The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 314:1–340
Lans H, Jansen G (2007) Multiple sensory G proteins in the olfactory, gustatory and nociceptive neurons modulate longevity in Caenorhabditis elegans. Dev Biol 303:474–482
Ludewig AH, Schroeder FC (2013) Ascaroside signaling in C. elegans. WormBook 18:1–22
Onken B, Driscoll M (2010) Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1. PLoS One 5:e8758
Petrascheck M, Ye X, Buck LB (2007) An antidepressant that extends lifespan in adult Caenorhabditis elegans. Nature 450:553–556
Greer EL, Brunet A (2009) Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans. Aging Cell 8:113–127
Omodei D, Fontana L (2011) Calorie restriction and prevention of age-associated chronic disease. FEBS Lett 585:1537–1542
Gelino S, Hansen M (2012) Autophagy—an emerging anti-aging mechanism. J Clin Exp Pathol 1–12
Levine B, Kroemer G (2009) Autophagy in aging, disease and death: the true identity of a cell death impostor. Cell Death Differ 16:1–2
Melendez A et al (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301:1387–1391
Niccoli T, Partridge L (2012) Ageing as a risk factor for disease. Curr Biol 22:R741–R752
Madeo F, Tavernarakis N, Kroemer G (2010) Can autophagy promote longevity? Nat Cell Biol 12:842–846
Blagosklonny MV (2010) Revisiting the antagonistic pleiotropy theory of aging: TOR-driven program and quasi-program. Cell Cycle 9:3151–3156
Rodier F, Campisi J, Bhaumik D (2007) Two faces of p53: aging and tumor suppression. Nucleic Acids Res 35:7475–7484
Calabrese V et al (2011) Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity. Mol Aspects Med 32:279–304
Martins I, Galluzzi L, Kroemer G (2011) Hormesis, cell death and aging. Aging (Albany NY) 3:821–828
Acknowledgments
We regret that not all original studies or reviews could be discussed here due to space limitations. Additional references to relevant works can be found in the cited reviews. N.V. is funded by the Italian Association for Cancer Research (MFAG11509).
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The corresponding author states that there are no conflicts of interest.
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Torgovnick, A., Schiavi, A., Maglioni, S. et al. Healthy aging: what can we learn from Caenorhabditis elegans?. Z Gerontol Geriat 46, 623–628 (2013). https://doi.org/10.1007/s00391-013-0533-5
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DOI: https://doi.org/10.1007/s00391-013-0533-5