REVIEW
Pharmacological maintenance of protein homeostasis could postpone age-related disease
Silvestre Alavez,
Gordon J. Lithgow,
Silvestre Alavez
Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA
Search for more papers by this authorGordon J. Lithgow
Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA
Search for more papers by this authorSilvestre Alavez,
Gordon J. Lithgow,
Silvestre Alavez
Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA
Search for more papers by this authorGordon J. Lithgow
Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA
Search for more papers by this authorSilvestre Alavez or Gordon J. Lithgow, Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA. Tel.: +1 415 209 2298; fax: +1 415 209 2232; e-mail:[email protected];[email protected]
Summary
Over the last 10 years, various screens of small molecules have been conducted to find long sought interventions in aging. Most of these studies were performed in invertebrates but the demonstration of pharmacological lifespan extension in the mouse has created considerable excitement. Since aging is a common risk factor for several chronic diseases, there is a reasonable expectation that some compounds capable of extending lifespan will be useful for preventing a range of age-related diseases. One of the potential targets is protein aggregation which is associated with several age-related diseases. Genetic studies have long indicated that protein homeostasis is a critical component of longevity but recently a series of chemicals have been identified in the nematode Caenorhabditis elegans that lead to the maintenance of the homeostatic network and extend lifespan. Herein we review these interventions in C. elegans and consider the potential of improving health by enhancing protein homeostasis.
References
- Adachi H, Ishii N (2000) Effects of tocotrienols on life span and protein carbonylation in Caenorhabditis elegans. J. Gerontol. A Biol. Sci. Med. Sci. 55, B280–B285.
- Alavez S, Vantipalli MC, Zucker DJ, Klang IM, Lithgow GJ (2011) Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature 472, 226–229.
- Alcedo J, Kenyon C (2004) Regulation of C. elegans longevity by specific gustatory and olfactory neurons. Neuron 41, 45–55.
- Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci. USA 90, 7915–7922.
- Anderson P, Brenner S (1984) A selection for myosin heavy chain mutants in the nematode Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 81, 4470–4474.
- Apfeld J, Kenyon C (1999) Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402, 804–809.
- Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L (2007) Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech. Ageing Dev. 128, 546–552.
- Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444, 337–342.
- Benedetti MG, Foster AL, Vantipalli MC, White MP, Sampayo JN, Gill MS, Olsen A, Lithgow GJ (2008) Compounds that confer thermal stress resistance and extended lifespan. Exp. Gerontol. 43, 882–891.
- Berger Z, Ttofi EK, Michel CH, Pasco MY, Tenant S, Rubinsztein DC, O’Kane CJ (2005) Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway. Hum. Mol. Genet. 14, 3003–3011.
- Cao S, Gelwix CC, Caldwell KA, Caldwell GA (2005) Torsin-mediated protection from cellular stress in the dopaminergic neurons of Caenorhabditis elegans. J. Neurosci. 25, 3801–3812.
- Carmichael J, Sugars KL, Bao YP, Rubinsztein DC (2002) Glycogen synthase kinase-3beta inhibitors prevent cellular polyglutamine toxicity caused by the Huntington’s disease mutation. J. Biol. Chem. 277, 33791–33798.
- Ching TT, Chiang WC, Chen CS, Hsu AL (2011) Celecoxib extends C. elegans lifespan via inhibition of insulin-like signaling but not cyclooxygenase-2 activity. Aging cell 10, 506–519.
- David DC, Ollikainen N, Trinidad JC, Cary MP, Burlingame AL, Kenyon C (2010) Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol. 8, e1000450.
- Davies AG, McIntire SL (2004) Using C. elegans to screen for targets of ethanol and behavior-altering drugs. Biol. Proced. Online 6, 113–119.
- Diomede L, Cassata G, Fiordaliso F, Salio M, Ami D, Natalello A, Doglia SM, De Luigi A, Salmona M (2010) Tetracycline and its analogues protect Caenorhabditis elegans from beta amyloid-induced toxicity by targeting oligomers. Neurobiol. Dis. 40, 424–431.
- Dostal V, Roberts CM, Link CD (2010) Genetic mechanisms of coffee extract protection in a Caenorhabditis elegans model of beta-amyloid peptide toxicity. Genetics 186, 857–866.
- Evason K, Huang C, Yamben I, Covey DF, Kornfeld K (2005) Anticonvulsant medications extend worm life-span. Science 307, 258–262.
- Fei YJ, Inoue K, Ganapathy V (2003) Structural and functional characteristics of two sodium-coupled dicarboxylate transporters (ceNaDC1 and ceNaDC2) from Caenorhabditis elegans and their relevance to life span. J. Biol. Chem. 278, 6136–6144.
- Gidalevitz T, Ben-Zvi A, Ho KH, Brignull HR, Morimoto RI (2006) Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311, 1471–1474.
- Gidalevitz T, Krupinski T, Garcia S, Morimoto RI (2009) Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity. PLoS Genet. 5, e1000399.
- Haldimann P, Muriset M, Vigh L, Goloubinoff P (2011) The novel hydroxylamine derivative NG-094 suppresses polyglutamine protein toxicity in Caenorhabditis elegans. J. Biol. Chem. 286, 18784–18794.
- van Ham TJ, Thijssen KL, Breitling R, Hofstra RM, Plasterk RH, Nollen EA (2008) C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging. PLoS Genet. 4, e1000027.
- Hamamichi S, Rivas RN, Knight AL, Cao S, Caldwell KA, Caldwell GA (2008) Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson’s disease model. Proc. Natl. Acad. Sci. USA 105, 728–733.
- Harrington LA, Harley CB (1988) Effect of vitamin E on lifespan and reproduction in Caenorhabditis elegans. Mech. Ageing Dev. 43, 71–78.
- Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395.
- Honda Y, Tanaka M, Honda S (2010) Trehalose extends longevity in the nematode Caenorhabditis elegans. Aging cell. 9, 558–569.
- Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300, 1142–1145.
- Keaney M, Gems D (2003) No increase in lifespan in Caenorhabditis elegans upon treatment with the superoxide dismutase mimetic EUK-8. Free Radic. Biol. Med. 34, 277–282.
- Kim YH, Rane A, Lussier S, Andersen JK (2011) Lithium protects against oxidative stress-mediated cell death in alpha-synuclein-overexpressing in vitro and in vivo models of Parkinson’s disease. J. Neurosci. Res. 89, 1666–1675.
- Kopito RR, Ron D (2000) Conformational disease. Nat. Cell Biol. 2, E207–E209.
- Kraemer BC, Zhang B, Leverenz JB, Thomas JH, Trojanowski JQ, Schellenberg GD (2003) Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc. Natl. Acad. Sci. USA 100, 9980–9985.
- Kwok TC, Ricker N, Fraser R, Chan AW, Burns A, Stanley EF, McCourt P, Cutler SR, Roy PJ (2006) A small-molecule screen in C. elegans yields a new calcium channel antagonist. Nature 441, 91–95.
- Lakso M, Vartiainen S, Moilanen AM, Sirvio J, Thomas JH, Nass R, Blakely RD, Wong G (2003) Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein. J. Neurochem. 86, 165–172.
- Lemieux GA, Liu J, Mayer N, Bainton RJ, Ashrafi K, Werb Z (2011) A whole-organism screen identifies new regulators of fat storage. Nat. Chem. Biol. 7, 206–213.
- Link CD (1995) Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 92, 9368–9372.
- Link CD, Taft A, Kapulkin V, Duke K, Kim S, Fei Q, Wood DE, Sahagan BG (2003) Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer’s disease model. Neurobiol. Aging 24, 397–413.
- McColl G, Killilea DW, Hubbard AE, Vantipalli MC, Melov S, Lithgow GJ (2008) Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans. J. Biol. Chem. 283, 350–357.
- Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, Wallace DC, Malfroy B, Doctrow SR, Lithgow GJ (2000) Extension of life-span with superoxide dismutase/catalase mimetics. Science 289, 1567–1569.
- Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, Strong R (2011) Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J. Gerontol. A Biol. Sci. Med. Sci. 66, 191–201.
- Miyasaka T, Ding Z, Gengyo-Ando K, Oue M, Yamaguchi H, Mitani S, Ihara Y (2005) Progressive neurodegeneration in C. elegans model of tauopathy. Neurobiol. Dis. 20, 372–383.
- Moy TI, Conery AL, Larkins-Ford J, Wu G, Mazitschek R, Casadei G, Lewis K, Carpenter AE, Ausubel FM (2009) High-throughput screen for novel antimicrobials using a whole animal infection model. ACS Chem. Biol. 4, 527–533.
- Novak J, Vanek Z (1992) Screening for a new generation of anthelminthic compounds. In vitro selection of the nematode Caenorhabditis elegans for ivermectin resistance. Folia Microbiol. (Praha) 37, 237–238.
- 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.
- Park KW, Li L (2008) Cytoplasmic expression of mouse prion protein causes severe toxicity in Caenorhabditis elegans. Biochem. Biophys. Res. Commun. 372, 697–702.
- Petrascheck M, Ye X, Buck LB (2007) An antidepressant that extends lifespan in adult Caenorhabditis elegans. Nature 450, 553–556.
- Pietsch K, Saul N, Menzel R, Sturzenbaum SR, Steinberg CE (2009) Quercetin mediated lifespan extension in Caenorhabditis elegans is modulated by age-1, daf-2, sek-1 and unc-43. Biogerontology 10, 565–578.
- Porta EA (2002) Pigments in aging: an overview. Ann. N Y Acad. Sci. 959, 57–65.
- Powolny AA, Singh SV, Melov S, Hubbard A, Fisher AL (2011) The garlic constituent diallyl trisulfide increases the lifespan of C. elegans via skn-1 activation. Exp. Gerontol. 46, 441–452.
- Reis-Rodrigues P, Czerwieniec G, Peters TW, Evani US, Alavez S, Gaman EA, Vantipalli M, Mooney SD, Gibson BW, Lithgow GJ, Hughes RE (2011) Proteomic analysis of age-dependent changes in protein solubility identifies genes that modulate lifespan. Aging cell. DOI: 10.1111/j.1474-9726.2011.00765.x.
- Saul N, Pietsch K, Menzel R, Sturzenbaum SR, Steinberg CE (2009) Catechin induced longevity in C. elegans: from key regulator genes to disposable soma. Mech. Ageing Dev. 130, 477–486.
- Sayed AA (2011) Ferulsinaic acid attenuation of advanced glycation end products extends the lifespan of Caenorhabditis elegans. J. Pharm. Pharmacol. 63, 423–428.
- Selkoe DJ (2003) Folding proteins in fatal ways. Nature 426, 900–904.
- Srivastava D, Arya U, SoundaraRajan T, Dwivedi H, Kumar S, Subramaniam JR (2008) Reserpine can confer stress tolerance and lifespan extension in the nematode C. elegans. Biogerontology 9, 309–316.
- Strong R, Miller RA, Astle CM, Floyd RA, Flurkey K, Hensley KL, Javors MA, Leeuwenburgh C, Nelson JF, Ongini E, Nadon NL, Warner HR, Harrison DE (2008) Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging cell. 7, 641–650.
- Tampakakis E, Okoli I, Mylonakis E (2008) A C. elegans-based, whole animal, in vivo screen for the identification of antifungal compounds. Nat. Protoc. 3, 1925–1931.
- Teschendorf D, Link CD (2009) What have worm models told us about the mechanisms of neuronal dysfunction in human neurodegenerative diseases? Mol. Neurodegener. 4, 38.
- Tullet JM, Hertweck M, An JH, Baker J, Hwang JY, Liu S, Oliveira RP, Baumeister R, Blackwell TK (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132, 1025–1038.
- Wilson MA, Shukitt-Hale B, Kalt W, Ingram DK, Joseph JA, Wolkow CA (2006) Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging cell. 5, 59–68.
- Wu Z, Smith JV, Paramasivam V, Butko P, Khan I, Cypser JR, Luo Y (2002) Ginkgo biloba extract EGb 761 increases stress resistance and extends life span of Caenorhabditis elegans. Cell. Mol. Biol. (Noisy-le-grand) 48, 725–731.
- Wu Y, Wu Z, Butko P, Christen Y, Lambert MP, Klein WL, Link CD, Luo Y (2006) Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans. J. Neurosci. 26, 13102–13113.
- Zengel JM, Epstein HF (1980) Identification of genetic elements associated with muscle structure in the nematode Caenorhabditis elegans. Cell Motil. 1, 73–97.
