1.

2. 3. , . , , : , , , , . , , , , . . , , . 4. 1 5. (, , ) , . , , , -, . (, ). : 106 ( ) 102 ( , ). : ( , , , ), ( ) ( ). . 90- XX , ( , , ). , , , . , . , (, , , ), , . , , , . .| | 6 (Gompertz, 1825). XIX , , , . . , . , Ceratitis capitata , . , , , 80 , 110 . (Helfand, Inouye, 2002). (Fisher, 1930) . (Medawar, 1946, 1952), . , , , , . , , , . . , , , . , , (Helfand, Inouye, 2002). , , - ( ), , , , . , : , , , . , , , , , (Williams, 1957). . - . , ( ), (Campisi, 2005). . (disposable soma theory) (Kirkwood, 1977). , . , , , . , , . , . (, , ) , , . , , (Lithgow et al., 1995; Murakami, Johnson, 1996; Guarente, Kenyon, 2000; Longo et al., 2005; Partridge et al., 2005a). , , (, ), (, , ). . , . XIX (Weismann, 1889). , . . . . XX (Dobzhansky, 1964), . |7| 6. . . QQ , . . (Marc Tatar) (Faculty of Ecology and Evolutionary Biology, Brown University), , , , ? , , , . , C.elegans , , , ? , , , .QQ C , . . Colubridae , ( ) . . , . . , , ( 15 ) / ( 10 ). .| | 8 (Anne Bronikowski) , (Department of Ecology, Evolution, and Organismal Biology, Iowa State University) , QQ (Stuart Jay Olshansky) , (Center of Aging, University of Chicago), . , , . , , , . -, , , , . , 3,1 , , 7,9 . , , .QQ , , , . , , . , , , , , , . Escherichia coli, , , . , , , , . , , , . , , , . , .c (Franois Taddei) TaMaRa, INSERM (TaMaRa Laboratory, INSERM), , |9| 7. QQ (Robert E. Ricklefs) , (Department of Biology, University of Missouri at St. Louis), -, .|10| , , . , . , , , , , . . , , . , , , , . , , , . , , , , , , , , . . , . , , , , - , , ( . ) , , . . . , , . , , ., , , , , . , - . 12 18 . , .QQ (Mikchel Rose) (University of California), (evolutionary radiation of Drosophila melanogaster populations). , , 2007 . , SENS, . , . . , . 1970- , . , , Methuselah flies. , . 1981 () - . : , , , . , , . , , , , . | 11 | 8. QQ (Bruce A. Carnes) , (Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center), .|12| , , ( ), (, . , ), , . , , , . (, ). , , , , 21 , 100 . () (). . . . , , : 1) , , , . , ; , , 2) , 80% 80 ; , 3) , , . , , , , , . . QQ (Vera Gorbunova), (Andrei Seluanov) (Department of Biology University of Rochester), , , , , . 10 . ( 30 ). 18 , 4 30 , . 2009 , p16, . . , . , . , , , . , , . , . - ; , ; Sir2 () . , , . , . | 13 | 9. QQ , , . (Rochelle Buffenstein) (department of physiology, Health Science Center, University of Texas UTHSC), , . , , . , , , , . , , , . , , , , , . . . : ( 40 ), , , , , . , , , , . . QQ , , - . , ( ) , , .QQ , |14| (Joanne Murabito) (Boston University School of Medicine), , . (Cohorts for Heart and Aging Research in Genomic Epidemiology, CHARGE). , . (Steven Austad) (Department of CellularStructural Biology, University of Texas Health Science Center), -, 38000 . , . . , , . , , . , , , 80 . . ( ), ( ) ( ). | 15 | 10. QQ , (Nir Barzilai) (Albert Einstein College of Medicine), , . , . , 95 . , , , , ( ) . , , , . ( , CETP, -3, APOC-3, ADIPOQ), , . - . ( ) , , ., IL-10 TGF-beta, IGF-1. IGF-1 . , p53. , p53, , . . , 100 , . (GEnetics of Healthy Aging, , GEHA). IGF-1 24 p53 . , . , . , . .QQ , - |16|QQ , , , . (Center on Aging, NORC and The University of Chicago), , ., , , , . (, , ) . . . , (20-25 ), , . (Claudio Franceschi) (Department of Experimental Pathology, University of Bologna), , . . , (100 ). , , , , , . , ( ), , , . , , . . , , . , , . | 17 | 11. QQ - . , (, 110 ) , , . (Craig and Brad Willcox) (Okinawa Research Center for Longevity Science, Okinawa, Japan) , 105 . , . , , . , . , , IGF-1. , FOXO3A, . , , , FOXO3A GG. , , , . . 2|18| 12. , , . , , , , , - . , : , , , , , . . , , , . , , -, , , , .. . , , , , . , , , .|20| , , , , .., , . , , . , , (.. , , ), , . | 21 | 13. QQ - , :QQ . (John D. Furber) Legendary Pharmaceuticals, , , 20 . Legendary Pharmaceuticals, , , . , , () . c . (Joao Pedro de Magalhaes) (Integrative Genomics of Ageing group, School of Biological Sciences, University of Liverpool).1) / / .QQ 2) (), . . : 1. , 2. . , , 3. , , 4. . , 5. . , 6. , , 7. , 8. . . 4) Heterocephalus glaber.2) 5) short hairpin RNA ( , shRNA), RNA interference (RNAi), . - , . 3) , - . -3) - , .QQ |22| GenAge database, , - , , . . (Pat Langley) (Arizona State University), , . : 1) , , , , . () . . (Andres Kriete) , (School of Biomedical Engineering, Drexel University), , , , - . | 23 | 14. . (Thomas Kirkwood) , (Institute for Ageing and Health Newcastle University), , , , . , . . , . . : 1) (- ) , 2) , 3) , , 4) , , , , 5) , , 6) |24| QQ SENS (Strategies for Engineered Negligible Senescence).1) . . 2) . 3) . 4) . 5) , . 6) , . 7) 10) , , . , .9) . 10 , : .8) , .QQ (Aubrey de Grey) SENS (SENS Foundation), , 7 , . , , , , , , . 7 : 1) , ;2) ; 3) (), ; 4) , ; 5) , ; 6) , ; 7) . . - , , , , , . | 25 | 15. QQ , 4. . (Daniel Promislow) (Department of Genetics, The University of Georgia) , , . , , . : 1. . . 2. , 3. : Saccharomyces cerevisiae Caenorhabditis elegans. , , , , . , , , , .QQ HSP-16.2 , HSP-16.2. , , . , , HSP-16.2 GFP- . HSP16.2. HSP-16.2 , HSP-16.2 GFP, . , , . , (). , . . (Depar tment of Biological Sciences, University of Southern California) -, (Thomas E. Johnson) (Institute for Behavioral Genetics, University of Colorado at Boulder) , QQ (John Tower)|26| . Drosophila melanogaster ., , - . , . , , , , , , . . | 27 | 16. QQ (Andrjez Bartke) (School of Medicine Southern Illinois University) , . , . , , , . , , . 14% 10 , 20-25 . .QQ , , . , , . , , , . , , ( ) , ., - , , , .GH deficiency or GH resistanceReduced Insulin SecretionImproved Insulin SensitivityReduced Hepatic and Peripheral IGF-1?Reduced Blood GlucoseReduced Metabolism and ROS GenerationDelayed Aging and Prolonged Longevity|28| ?Reduced Cancer Incidence (Karl Lenhard Rudolph) (Department of Molecular Medicine, University of Ulm) , , . , . , , . , , , . , . , . . , , , . 4 (LL-37/CRAMP, STMN-1, EF-1, Chi3L3), . , , , . .QQ - (, , ). .; , , . 2,5 . , 70- , . 4,5 , 10 10 : -; 4,5 ; 3,3%. , (Teresa Seeman) (School of Medicine, University of California, Los Angeles) -, | 29 | 17. QQ AGE - AGE ( ) , AGE , . : , , , , . (, AGE ) , , AGE . . Schematic reaction scheme of AGE formation ProteinSchiff BaseGlucoseQQ (Andreas Simm) -, (Medical Research Center, Martin Luther University of Halle Wittenberg) , Namiki PathwayWolff PathwayROSGlycolysis Metabolism Fatty acid degradation Amino acid degradationFructosamineROSROSGlyoxal MethylglyoxalROSAGEs ProteinQQ -6 : -6 (IL-6), TNF-a, IL-1. . (Luigi Ferrucci) (Clinical Research Branch, Harbor Hospital) , |30| 473 IL-6. IL-6, , , . , , , , , . , , . 2- . (Vladimir N. Anisimov) . .. (Cancerogenesis and oncogerontology Department, N.N.Petrov Research Institute of Oncology), , QQ IL-6. . , , . , IL-6 ( ), . IL-6 - , IL-6. . . (Alexey Ryazanov) (Department of Pharmacology, Robert Wood Johnson Medical School), , , . . . , , . , , . | 31 | 18. QQ , , . , . , . . . (Stephen Spindler) , (Department of Biochemistry, University of California), , . , , (), .QQ , mTOR, , FOXO, PTEN AMPK . TOR. TOR, . Roswell Park () , , . , ( , , ). , ( TOR) . , . , TOR, . . |32| (Mikhail Blgosklonny) , (Department of Cell Stress Biology, Roswell Park Cancer Institute), , 3 19. , , , . . , , (. .). . , , , , , . , . , (0,1 Gy) , . : , , , , .|34| FG2 4n 2n 2n SG1 , , . . , , . G0 . . 50-70 . , . , , . , . (, ) - , , ( ). , , . G0, , . , , . , , . , . , . , , , . , . , , , , , , . , . , . , . , , , , , . : , ( ). , . , . . , , , . , : 1) , , , ( ) 2) , , 3) . , . , , , . ( ), . , , . . | 35 | 20. , QQ , - , , , . (Elizabeth Blackburn) (University of California), . 1980 , . , 1985 , . 2009 . , . . , , , . |36| , , . , , , , , . , , , 10 , . , . , , , , .QQ - 38 , , , . (David Kipling)Helicase (Department of Pathology, Cardiff University), , .WPNNo helicase activityG-quadruplex not degradedTelomere Shortening - p38, . - p38 . 38 -Exonuclease Disrupted repair mechanismGenomic instabityPremature Aging . , , SB203580, , . SB203580 .QQ , (hTERT) , (Alternative Lengthening of Telomeres ALT). , , . , , (promyelocytic leukemia (PML) bodies), (.. TRF1 TRF2) . , . , . . (Roger Reddel) (Medical school the University of Sydney), , . | 37 | 21. QQ QQ TRF 1 . (Tim Spector) , (Department of Twin ResearchGenetic Epidemiology, Kings College London), , . , , , ( 12 ) . 2401 , 2152 , 249 . , , , , , 200 .. , . , , . , 1122 18-76 , 27 (..) . , , 240 .. , . , 5 .. .QQ . , Salmonella , ? , Salmonella . , enterica , . . S. enterica , , . , . . () |38| , (shelterin) , . (Titia de Lange) (Laboratory for Cell Biology and Genetics, The Rockefeller University), -, . TRF1 TRF2 , - TRF1, - TRF1 . , . , . . . , . .QQ . , . (Petteri Ilmonen) . (Konrad Lorenz Institute for Ethology), , . . , . , , . , , , , , . , , . (Mamoru Satoh) , (Division of Cardiology, Department of Internal Medicine, Iwate Medical University School of Medicine), , . | 39 | 22. QQ QQ (David Gilley) (Department of MedicalMolecular Genetics, Indiana University), , / , , . 686 ( ) 7385 . 71 .. . . , . . , , .QQ , , . , . , |40| , , . in situ. , . , . (Peter Rabinovitch) . , (Department of Pathology the University of Washington School of Medicine, Fred Hutchinson Cancer Research Center), , . (William Andrews) (Sierra Sciences), , , . , , . , , . , . . , , , , . , , , . . 2008 , , . , 50%, , , . , , , . , , , . - 33 , , . , , , . , , , , , . , , , , . , , . , , , , . . -65 Sierra Sciences. , , 200 29 , . , , . , . ( -65). ( 4000 ), , . | 41 | 23. , (telomere uncapping) , . (uncapped telomeres) . - , (DNA damage loci) , p53. , , in vivo. Chronic inflammation Anti-inflammatory treatment Increased ROS productionQQ ?Impaired telomerase activityAnti-oxidant defence Increased base oxidation Enhanced DNA repair, PARP enzymes, -, . , . (Thomas von Zglinicki) , (Ageing Research Laboratories, Institute for Ageing and Health, Newcastle University), , . . : , . - . .|42| Persistent damage to telomeres , , , . , (). - , , .Faster rate of telomere shorteningCell senescenceFaster rate of biological agingQQ Nrf2 NFkB , , . - . , . , . (Mustafa Lokhandwala) (College of Pharmacy, University of Houston), , ( ) . , , . , , . | 43 | 24. QQ SkQ1 , (ROS), . (Vladimir P. Skulachev) .. (Bioinformatics and Bioengineering Department, Moscow State University), , . SkQ1, . SkQ1 . , . in vitro , SkQ1 , . , SkQ1 HeLa , 22, Podospora anserina, Ceriodaphnia affinis, , . , SkQ1 , , , , , , , , , . , SkQ1 .QQ Nrf2, , , . , , , , (Brassica oleracea italica), .|44| QQ Nrf2 , . : keap1 Nrf2. keap1 Nrf2 . (Paul Talalay) (School of Medicine, Johns Hopkins University), , , , . (Nader Maghsoudi) (Shalid Beheshti university of medical sciences), , NT2 . , , , . , . , , : Hsp-70, -GCS Nrf2. , , .QQ , . , , 7,8--8. , , . , . , NEIL1 NEIL2. . , . , , . , , . , -, 7,8--8- , , . in vivo, , . -, . . . (Istvan Boldogh) (Department of MicrobiologyImmunology,The University of Texas Medical Branch), , | 45 | 25. QQ SKN-1 SKN-1 , . (Keith Blackwell) . (Department of Pathology Joslin Diabetes Center), , , . SKN-1, . , FOXO, , . C. elegans , FOXO (DAF-16) . , SKN-1 , . , SKN-1 , . , 1 . , C. Elegans, .INSULIN/IGF-1PI3KPFOXOP PP PPAKTFOXO-- , (Department of Cardiology, National Heart, Lung, and Blood Institute, NHLBI) , PPSGK (Toren Finkel) (20% ) () ras , . , , , . . , , ras , H2O2 , . . , ras , . in vitro . Ras . , ras , , , . . , , ras , rac1.INSULIN/IGF-1PDKIQQ Ras , (.. , , 1%) ras p21 . . , , . , - . , , . . FOXO . , FOXO .|46| | 47 | 26. QQ Q10 (Fanklin Rosendeldt) (Department of Cardiothoracic Surgery, Alfred Hospital) , , , Q (CoQ) . ( in vitro, in vivo). 14 (- , -3 ) , CoQ. , , . , , , CoQ , , . 100 ( 68 ) , . CoQ 2QQ , . . , , . in vitro , .- . , , , , . . , , , . |48| (Dean Jones) (Lungs Department, Emory University School of Medicine) , QQ , SKN-1 (Thomas E. Johnson) (Department of Integrative Physiology, Institute for Behavioral Genetics, University of Colorado), , , , . 2008 (American Aging Association). , SKN-1. SKN-1 MKK-4, IKKe-1, NEKL-2, PDHK-2 , SKN-1 . .QQ CoQ , Q Q9 Q10. . , clk-1 CoQ, . , , . , . elegans, CoQ, , . , , , 60% CoQ . . clk-1 C. elegans . clk-1 CoQ . , CoQ clk-1- CoQ. . CoQ . , . , Q8 , . (Cathy Clark) (Department of ChemistryBiochemistry, University of California, Los Angeles) , | 49 | 27. QQ , Chlamydo onas m Polytomella sp. , . : , . (Michael King) (Thomas Jefferson University), , . , . , , . , , , . .QQ Nrf2 , . Nrf2 . (Suresh I.S. Rattan) (Department of Molecular Biology) (University of Aarhus), , ., MG-132 , ) - : R-- .- , .|50| Nrf2 ARE QQ - - - . , . - . , Nrf2 , .Keap1 , , . , , Q10 - . , - . Nrf2. , Nrf2, .b) Keap1 Nrf2ARE (Bruce Ames) (University of California), , R-- , .Nrf2Phase II Enzyme Proteasome Nrf2 Mg132Nrf2 Mg132 Nrf2 ARE | 51 | 28. QQ NAD(+) QQ . , . (George Roth) , (National Institute on Aging, National Institute of Health), , , . . 300 . . , . 2-, , . , 2- , 30% , , . , -- (Su-Ju Lin) , , (Department of Microbiology, College of Biological Sciences, University of California), , Sir2 () NAD(+) ( ) -, , , . , , NAD(+) . , . - - . NAD(+) , Saccharomyces cerevisiae. NAD(+), . , , . , , , , .QQ . , , . , , , , -|52| / . . , , . , .NAD+ (Arlan G Richardson) (University of Texas Health Science Center at San Antonio's), , DI- and TRIPEPTIDEInsulin/IGF-1 signallingRAPTORDAF-16/FOXOTSC1 TSC2TORSIR-2/SIRT1 | 53 | 29. QQ 2- , . (Donald K. Ingram) , (School of Human Ecology, Louisiana State University), -, . , . 2- , . 2 . , . QQ AMPK 20% , . , . , 2- , - , . - , , -. , - , 950 , 160 , , S6 1 (S6K1). , 20%. . , , S6K1. , S6K1 , , . S6K1 S6K1 , AMPK, , . , , , , (, , ). . , , AMPK, 2- . |54| QQ (Dominique John Withers) (Division of Medicine, University College London,), , . , , . (JeffreyKeller) , (Louisiana State University, Pennington Biomedical Research Center), -, - (UPP) . , , , , ., 20S (POMP-1). . , UPP . , , , .QQ , , , , . , . , . , , , , . , . (Michael Pankratz) , (LifeMedical Sciences (LIMES)Institute, University of Bonn), , . | 55 | 30. QQ (Stephen Spindler) , (Department of Biochemistry, University of California, Riverside), , . , , , . , , , , , . , , , , . . , , . . - -1 (IGF). (), . , IGF |56| , . , , , , , - , , ; , , . , , , . , , , , . , , , -Q . - (DNA microarray). 8 . , , 75% , . , .QQ , RES , N , , . . RES B6C3F (1) . 40% , N ( , , (N), , , (), , (RES; . 1,25 ) 2- 5- . , N, , Foxo1 N. . (Tomas Prolla) - (University of Wisconsin Madison), , .QQ , , , . (Antonio Zarzuelo) , (Faculty of Pharmacy, University of Granada), , . , . , , . . (+) , , , , , , , . . , | 57 | 31. QQ , . QQ , ` , - .B1/B6. , (1) , , 6 . , , , . , . , , . ` , (Peter J. O'Brien) , , . (Department of Pharmaceutical ` Sciences, Faculty of Pharmacy, University , . of Toronto,), ` , . . , , , , , , . : , .|58| , (- L-) . (Alan Hipkiss) (GKT School of Biomedical Sciences, Kings College London), . , , , , ., , . , . (carnosinylation). , , . . The metabolic pathway of carnosine-alanineAnserine, OphidineMethylhistidinesMethylationCarnosineCarnicineInteraction with the free radical productsEnzyme HydrolysisHistidine-alanineSynthesis of CoA, nucleic acids, stimulation of collagen synthesisDecarboxylationHistamineMediator function, participation in the allergic and inflammatory reactions | 59 | 32. QQ MsrA (Jackob Moskovitz) , , (Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, United States), , . - (MsrA) . , - . MsrA . , , , , . MsrA . , , , . , . MsrA , , . , - , , . .QQ - (3--1-2--5-) , , . in vitro . -|60| , , . , - . , , , . (Giancarlo Aldini) , , (Dipartimento di Scienze Farmaceutiche P Pratesi, University of Milan), , QQ (Simon Pyke) , (Department of Chemistry, University of Adelaide), . , . , ( ), . , . , , . , 1- () . , in vivo. , , , , .QQ - ( , , , .), ( , , .). , / . - : , (, , ), . , -. (, ) . . , - . (Stephan Schneuwly). (Edmund Maser) , (ChristianAlbrechts-University, Institute of Toxicology and Pharmacology for Natural Scientists), , | 61 | 33. QQ - -, (, , ) (, , ). . , . (, , , , .), , , . - . . , , , (, ). (Yorishige Imamura) , (Department of Biopharmaceutics, Kumamoto University), , , QQ hsp . , hsp70 . (Alexzander A. Asea) (Division of Investigative Pathology) (Proteomics Core Facility) ScottWhite Hospital.|62| . : , , (), , , , , , , , ( ), . , (Vittorio , Calabrese) L-/ -L-, , , , . (University of , Catania, ). hsp. , , , hsp- , . , hsp70 hsp90 .QQ , . , hsp . , hsp. hsp70 , . ( ) hsp70 , hsp72. , hsp70 . QQ , , , , . (Hansruedi Beler) , (University of Zurich), . hsp70 ( MPTP). hsp70 . . hsp70 , . , , . . | 63 | 34. QQ QQ , , , . Hsp vaccineinflammotory signal (Jeffrey Keller) (Stuart Calderwood)DRAINING LYMPH NODE (Harvard Medical School), , .Hsp secretion (University of Kentucky), , . , , , , . , , , , .QQ CD8+ cellCD4+ cellActivated CD8+ cellTUMOR . , (hsp) , , . . , hsp , . , hsp70 -6. , CD4 CD8- , . hsp60 70 , , hsp70 , - . ( hsp70). ,|64| , . , , 1 (MMP-1), ( , ), . , c-Jun AP-1 , . , . , . , , . . , . , Phaeodactylum tricornutum . . , , . (Bertrand Friguet) , (University Paris), ., , , , . Phaeodactylum tricornutum . | 65 | 35. QQ DExpression levels? Function?Free/not assembledB ( , ). (Institute of Biological Research and Biotechnology), .PROTEASOME . , . - SV40. . , ( J). - (Fu Shang) , (Human Nutrition Research Center on Aging, Tufts University), |66| , -8 . , , .INACTIVE INTERMEDIATES19S Reduced expression levels+ Hsc73Reduced abundance 11S+?ACTIVE PROTEASOME-subunitsPROTEIN EXPRESSION LEVELSE AGE-RELATED PRODUCTS/PROTEINSReduced activities Reduced assembled proteasome Altered subunits (post-translational modifications)Reduced ability to assemblePA 200Other proteins? Age-specific-ones?Rate-limiting (reduced expression levels) INHIBITION by lipofuscin/ ceroid and oxidized products (directly on catalytic sites) INHIBITION by age-related proteins?C (Chondrogianni and Gonos, 2005): , (A); (B); , (C, D); - , (E).QQ . .QQ . () , -8 (, ).+ POMP (hUMP1)Loss or malfunction of transcription factor(s)? , beta-5 . , WI38/T, , hUMP1/POMP . , . .ATPases activities?ASSEMBLY-subunits beta-5 . (Efstathios S. Gonos)PROTEASOME REGULATORS . (Pramod K. Srivastava) (University of Connecticut), . . MHC I . , HSP-, , - , . Antigenics, hsp, . , , HSP- . | 67 | 36. QQ (Russ Thomas Hepple) , (University of Calgary), , ( ) . , . , , , , , , . , , . .Possible targets Circulating factorsAnabolic factors (IGF-1)Atrophic factors (TNF, IL1)PI3KUnknown stimuliReactive oxygen species IKKIntracellular effectorsAkt p38 MAPKNF-kappaB FoxOAP-1UPS componentsAtrogin 1/MAFbxMuRF1Muscle atrophydirect stimulationtentative stimulation multistep stimulation, |68| Other UPS components (proteasome, EII, Ub...)(musculus plantaris) . , , . - MuRF1 MAFbx, , . , , , 2 . , , . , . , . .QQ , , F344/N x BN. , , Bax, Bcl-2 . . -. , - , , , , , ( ), . , . , (soleus) - . (Eric Blough) , , (Marshall University), . , - , . . | 69 | 37. QQ Drosophila melanogaster . , Drosophila melanogaster. , (43-47 ) 20S, (1-32 ) 26S. , (Maria E. FigueiredoPereira) (Hunter College of City University of New York), . 50%, 26S -. . , .QQ EGCG , (EGCG) , , , . , EGCG |70| Caenorhabditis elegans (35, 13,1%) ( 177,7%). , , hsp-16.2.Hsp73 H+H+H+ ? QQ - , , , , , 26S . . Hsp73Terman et al., 2007 - , PSI , . . . (Baolu Zhao) . (Institute of Biophysics), . (), hsc70: Q12KKEL, Q58FREL, IKLDQ111. , , . , . . , , , -, , . , hsc70, -, . , , , . . , - , 3- . . . (William Dunn) , , (Department of Anatomy and Cell Biology, University of Florida, College of Medicine, Gainesville, Florida) | 71 | 38. QQ Atg4D-Atg4A (Jon Lane) (University of Bristol), , () , , Atg4D . , , . , . , , , . , Atg4D . . (Albert Einstein College of Medicine), LAMP-A. . , , - , . |72| 9 , 14 . . , . , , , .Atg4A-Atg4D . Atg4D . Atg4D, . . , . Atg4A-Atg4D .QQ LAMP2A (Ana Maria Cuervo)QQ atg7 atg12 , 22 ( 80 ) LAMP2A . , . , , LAMP-2A , . , . (Shengkan Jin) (Robert Wood Johnson Medical School), , atg7 atg12 , . . . , ( ) : , . , . , , . , , , . | 73 | 39. QQ (STG1) , ABCA4 (ABCR). . . (Rando L. Allikmets) , (Department of Ophthalmology, Columbia University), New York, USA , ABCA4d Abca4 -/- , . (EIAV) , ABCA4 LacZ, (CMV) (Rho) . 1 . . , . 8-12 , . 3-5 . , , ABCA4.QQ beclin1 beclin 1 . : , , , . Beclin1 . beclin-1 . beclin-1 . Beclin-1 BH3 , |74| QQ Atg8a Bcl-2. , Beclin-1 /Bcl . Beclin1 , Bcl-2/Bcl-XL Beclin-1 . Bcl-2/Bcl-XL-beclin-1 . , ( ) , , , Bcl-2/Bcl-XLbeclin-1. (Beth Levine) (The University of Texas ), , (Dave Schubert ) (Salk institute), , Atg8a , , , . . , Atg8a, , . , . Atg8a , ( 4- ). . , , . , . QQ - - , . , , . , , - , . . , , . , . . , - (Ralph Nixon) - (Departments of Psychiatry (Brain Aging COE-Fac) and Cell Biology, The New York University School of Medicine ) -, . , . | 75 | 40. QQ 1993 , .elegans. , , , , , . eat-2, : TOR, RAB-10 PHA-4/FOXA eat-2 TOR RAB-10, . . (Cynthia Kenyon) . , , , , . ? , - bec-1 vps-34, , . , (Department of Biophysics and Biochemistry, University of California), -, , . , .QQ - - . , - () LAMP2A. , , - - . . LAMP2A . - , . LAMP2A, . , , . . .QQ (Alice Y.-C. Liu) , , (Rutgers University, USA)|76| , c (Department of Cellular and Molecular, Physiology; Tufts University School of Medicine, BostonQQ UCH-L1 - , , , : rab-10 () pha-4 (). , ( ), , , hsp70 -1. . . . (James Dice) (Keiji Wada) , , , (Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo Japan) . -- L1 (UCH-L1). , I93M . , UCH-L1 - , LAMP-2A, hsc70. I93M . . - . , GAPDH, , . , . , , . | 77 | 41. QQ TOR C (Savannah Sarkar) (Cambridge Institute for Medical Research), . TOR . . TOR , .nutrientstranslationautophagyTORstarvationinduced gene transcriptionribosome biosynthesis stability of high affinity amino acid permeasesstability of general amino acid permeases TOR , , : TOR .QQ - - MEF2 (myocyte enhancer factor 2), , . MEF2 ,, D. MEF2 . MEF2D . , MEF2D - . -, . MEF2D 40% ( |78| QQ -1 - ). hsc70 - MEF2D , , , . , - . , - - , - . (Zixu Mao) , , (Department of Pharmacology, Department of Neurology, Emory University School of Medicine, Atlanta) . (Susan A. Slaugenhaupt) (Associate Professor of Neurology Harvard Medical School), . (Center for Human Genetic Research Massachusetts General Hospital). , , -1 (transient receptor potential mucoipin-1, TRPML1). l IV (MLIV), TRPML1 . , TRPML1, TRPML2 TRPML3, , , . IV (MLIV) . , MLIV LAMP2A, . -1 2000 . , - . , , . -QQ - . , , , , - . , . , , KFERQ , 41%, , , KFERQ, - 38%. (). LAMP2A hsc73 25 81% . , , , , , . - . (Harold August Franch) , , (Director, Emory Kidney Stone Prevention Clinic, Emory University School of Medicine, Atlanta, Georgia) | 79 | 42. QQ - , . 53 30 LAMP2A. , , . , , . , , .. . - , - . , . . -, . , , . , (David Sulzer) , , , - ) (Depts. NeurologyPsychiatry, Columbia University, New York, Dept. Neuroscience, New York State Psychiatric Institute)QQ (Gabriel Travis) , -, (Department of Ophthalmology, University of California at Los Angeles School of Medicine, Los Angeles, California, USA)|80| , - (ABCR). ABCR , . . abca4 . , , . QQ - , , abca4(-/-). , . , abca4(-/-), , , . , ABCR4, , . - (LINCL) CLN2, (TPP1), . - , , , . - , , LINCL. TPP1 LINCL. , . . , . . (Beverly L. Davidson) , (Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, USA)QQ (Sandra Lee Hofmann) , (Department of Internal Medicine and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, USA), . (- PPT, CLN1), - (INCL). , . , INCL , ( , , - , , , ). - ( PPT) . , . , , -, . PPT . , , INCL. | 81 | 43. QQ 3 , ; . - (LINCL) CLN2, -I (TPP-I). , , CLN2, AAVrh.10hCLN2 ( rh.10, CLN2 ), . . CLN2 (2-, 3- 7-). TPP-I . TPP-I , . 376 , 277 , 7 168 , , 121 . (Ronald Crystal) , (Department of Genetic Medicine, Weill Cornell Medical College), , , , , .QQ , , .. . , . , . , , , . , -, - - (Manuel Maria Paula-Barbosa) , (Porto Medical School, University of Porto, Portugal)|82| - , , . , 6 , 20% . , , 20% . , . , , , , . (Dengshun Wang) (Department of Pathology and Laboratory) (Medicine University of Wisconsin), . .QQ QQ , , , , . . , - , . , . (Roscoe Brady) (National Institute of Health). ( , , -, -), . - , , , , , . , . , - 1. , ( , , -4-, , , ). . . , - . . . | 83 | 44. QQ (David Rubinsztein) , (University of Cambridge, Department of Medical Genetics , Cambridge Institute for Medical Research), , . . , , . , , . , . mTOR ( ), . D. melanogaster , . , CCI-779, . . , , - . 253 , : Ca2+ L- (, , , ), K+ATP , Gi , .QQ -- --3 , , , . ( ) . , , , , . , , , . , , -|84| QQ -- -3-, . (Department of Biochemistry and Biophysics) (University of North Carolina, Chapel Hill), , . , , SOD1. , . , . , () . SOD1 , (.. - ) . SOD1 , . QQ - , , , , . , , , , , . , . (Nikolay Dokholyan), , (, , . folding) , . oe e (SOD1), oe (Amyotrophic Lateral Sclerosis). - . (Vincent M. Monnier) (Institute of Pathology, Case Western Reserve University), , - , ., -, TAI (Tau Aggregation Inhibitors). (), - , - . , (). 2002 .. TauRx Therapeutics, TAI . Rember (2009 ). (Claude Wischik) (University of Aberdeen), , TauRx Therapeutics, . | 85 | 45. QQ . . (Om P. Srivastava) (department of vision sciences) (The University of Alabama at Birminghem), , . : -, , , ; - . , in vitro -D- -, -. in vivo, . , , . , -D, -, -. , . A3/A1 B1. . , -D- . 2 , . ( , ..). . . . () QQ NFkB (Merry Oursler) , (Department of Biochemistry and Molecular Biology, Mayo Clinic), , . , , . , , (TGF-). , , . TGF- , , NFkB .QQ JNK- , (NASH). , , , NASH- . , , SpragueDawley 6 , 35% |86| NFkB- BclXL Mcl-1, .(CD-) 71% (HFD). , . , , HFD- () NASH, , . , JNK, - Bcl-2 , .- (Xiang-Dong Wang) , (Nutrition and Cancer Biology Laboratory, Human Nutrition Research Center on Aging at Tufts University), , | 87 | 46. QQ NFB (Celine Gelinas) , , -, . . , (Center for Advanced Biotechnology and Medicine, Department of Biochemistry and Cancer, Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey), , . , NFB . , NFB . , . , , NFB, . ( ) (TNF) NFB-. , NFB , . / . NFB NFB- .Cell autonomous role for NF-B in tumor cellsQQ (Edward Mocarski) (Stanford University School of Medicine), , ., -, . , vMIA , , , . GADD45alpha: , , -, . . - vMIA, HtrA2/Omi. UL37, vMIA . , vICA, (Fas). 8- . vMIA -8 Bid, . vMIA . , G0.Paracrine role for NF-B in the tumor microenvironmentIncreased tumor cell growthResistance to apoptosis, Cell proliferation Production of inflammatory cytokinesActivation of innate immune responceRelease of HMGB1 and other pro-inflammatory molecules NFB.Necrotic tumor cells , . HMGB1. , , .|88| | 89 | 47. QQ . . , . , , , , . , , , , , . , . , , . , (Ferruccio Galbiati) , (University of Pittsburg, USA)|90| . , -1 ; -, , , . , -1 . , -1 , (Sang Chul PARK) (Aging and Apoptosis Research Center, Seoul National University College of Medicine), , .QQ - , . . , , QQ , -1. in vivo , . , . , . , , . HEK293T -1. , -1 , . (Andrew Quest) (Center For Molecular Studies Of The Cell, Universidad de Chile, Facultad de Medicina), , QQ -1 . -1 , . (Gerard Pasterkamp) (Experimental Cardiology Laboratory, University Medical Center Utrecht), , . . 30 - . CAV-1. , -1 . -1 , , , , . -1 . - | 91 | 48. QQ , . , , , (Reuben Harris)-, , , -, -, , (4-6)-, , : -, - , () () , , , , , (: - , - , - ( ). (4-6)- (4-6)-).QQ C.elegans C.elegans. (David Gems) C.elegans (C.elegans aging Lab, Institute of Healthy aging UCL), .|92| , , . . , 2-3 . C.elegans . . , , , . , , , (Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, Center for Genome Engineering, University of Minnesota), , . . , . , ( APOBEC3) . . , L1, , . , , , . QQ , APOBEC3G (A3G) . A3G (), (). CD4+ T A3G . A3G 5 15-Ma, . , , , A3G . , Alu Y , . , A3G L1- Alu. L1, Alu L1. (Warner Greene) (Gladstone Institute of Virology and Immunology), , , Alu hY A3G, , A3G . | 93 | 49. QQ (Vera Gorbunova) (University of Rochester, Department of Biology), , . . G1, S, G2, M . . L1 , (arrested cells), , L1 . , , L1 .QQ - -, . , () , . , . . , .|94| (Jan Hoeijmakers) , (Genetics Department, Medical Genetics Cluster at the Erasmus Medical Center), , . . , . . /. , (NER). , NER , . . . NER, , , ERCC1/ XPF , , XPC . . NER . , , NER-, , . QQ - - -, . , ( , ). , . . , - I.QQ . (Christi A. Walter) (Department of Cellular and Structural Biology, Health Science Center at San Antonio, The University of Texas), -, . ( ). pi, Piwi, . , Piwi- , , . , pi, . , pi , , , . (Alexei Aravin) (California Institute of Technology), , | 95 | 50. QQ - , , , , , . : (Brian Kennedy) , (Department of Biochemistry, University of Washington) , 1. , , , . , , . GCN4, , ( ). GCN4, . , GCN4 . . . mTOR. , . 2. , NAD+ , ADP. SIR2 , SIR 2.1, . , , , SIRT1, . |96| SIR2, , , . . , SIR2 , . 3. S6- S6 , . . S6- . , S6K1 - S6K1. , S6K1 . 4. . , . . , , . . .QQ , , , . (Prescott Deininger) , (NIH Center of Biomedical Research Excellence in Cancer Genetics, The Louisiana Cancer Research Consortium), , , . . LINE-1 L1 (Long Interspersed Element-1) , , (a flap intermediate), ERCC1/XPF LINE-1 , , , . XPF , ERCC1 . , , , , (non-length terminal repeat retrotransposition), LINE-1. , , ERCC1/XPF .QQ . , , , . LINE-1 Alu, APOBEC3G APOBEC3F LINE-1. A3A, A3B A3C , LINE-1 Alu, A3F A3G . , APOBEC3, APOBEC3B APOBEC3C APOBEC3. (Bryan Cullen) (Department of Molecular Genetics and Microbiology, Duke University Medical Center), , . | 97 | 51. QQ , . (Jan Vijg) (Albert Einstein College of Medicine, Department of Genetics) , , . . ( 34- ). 4-6 . , . . . . , . , , lac Z. . , ( . ) ( LacZ) , . QQ Parp1 Parp 1, , , . , , , , . , Parp 1 . - -. |98| Parp 1 . , . Parp 1, Parp 1 , , . , Parp 1 , . (Alexandr Buerkle) (Laboratory of Molecular Toxicology, University of Konstanz) , QQ (Konstantin Khrapko) , (Gerontology Division, Beth Israel Deaconess Medical Center, Johannes Gutenberg-University), , , , : . . , , . . . , -, . : . - . .QQ . , , . . , - : - . , , - , . , , , -. , , - . -. (Judd Aiken) , (School of Veterinary Medicine, University of Wisconsin), , - , . | 99 | 52. QQ 10 QQ 10 , C. elegans. age-1, 3- (PI3K(CS)), . , , 145-190 20 , 10 . , , . (Robert J. Shmookler-Reis) , (Departments of Geriatrics, University of Arkansas for Medical Sciences), , QQ , (Linda Partridge) (UCL Institute of Healthy Ageing), |100| , , , . . C.elegans . . 50 . , , , , . , , . , , , , . . , . , 10 , . , - Rim15. . , . , : (Ras2, Tor1 Sch9) . (Valter Longo) : , , , . , (Leonard Davis School of Gerontology, University of Southern California), , Ras2, Tor1 Sch9 , ( ) .QQ MOS1 (Corinne AugEGouillou) (Universit Franois Rabelais de Tours), , . Mariner (MLEs) , . in vitro , in vivo, - . Mos1, Drosophila mauritiana, in vitro 80 120 .. , , Mos1, . , , , .TransposonDonor plasmid Transposase bindingTransposon excisionBinding of the transposontransposase complex to another DNATransposon integration Mos1 | 101 | 53. QQ RecQ , , . . (Robert M. Brosh) (Laboratory of Molecular Gerontology, National Institute of Aging), . . . , , , , . , , (Werner) , . 30-40 , , (Bloom) . , , 1,5 . , . . , RecQ . ., , RecQ Wrn - . , , Wrn, (8-2) . . QQ , , 7 R. . , . , , , . , - (-) . . (Bruce C. Richardson) (Department of Internal Medicine, University of Michigan) , - CD4 + -, , .. In vivo . CD4 + CD28 - (University of NebraskaLincoln), QQ JNK - , - , - .|102| (Janos Zempleni) . , . , ERK JNK CD4 + CD28 . , , , ERK JNK CD4 + CD28 , , , Dnmts , , . , JNK- , . | 103 | 54. QQ , . TRF2 (shelterin complex), . , TRF2 , . TRF2 , . , TRF2 PRMT1, PRMT1 in vitro in vivo. PRMT1 , . PRMT1 TRF2 . (Xu-Dong Zhu) (Department of Biology, McMaster University), , .QQ - . , , . CpG , . - (Jean Pierre Issa) , , , , - ( (Department of Leukemia, M. D. ), Anderson Cancer Center, The University . , of Texas), , . , , , , . . , . -|104| QQ HDAC CK2. HDAC3 . . , HDAC8 , HDAC3 - , - . NCoR/ SMRT, HDAC LAQ824 LBH589 , , HSP90, , . (). , ER, MYOD1, IGF1 N33, , . HLTF , , ( 81 ). . . (H. Lee Moffitt Cancer CenterResearch Institute), , .QQ , . CpG O6- . . . , . (Eduard Seto) (David Sinclair) (Department of Pathology Harvard Medical School), , . . , , (ERCs) Sir2 . NAD+ , . , , () . , , , , , , , , .. . | 105 | 55. QQ (Richard I. Morimoto) - (Northwestern University), . . 1985 . SIRT1 ( 1). HSF1 (Heat shock factor 1) , , . , . SIRT1 ( ) HSF1 hsp70 HSF1.ribosometranslocationmisfolding folding90 7070specialized clients7090GA70general clientsHSnuclear import/exportQQ , , 3, , Sir2 . , , 3, . , , . , 70 27degradation70 70 refoldingproteasome70 , .|106| , . (Wistar Institute University Pennsylvania), , .- , , , , , . .QQ 90 misfolding (Ronen Marmorstein) (Charles Brenner) (Carver College of Medicine University of Iowa), . () , - , (). , (NR, nicotinamide riboside) , , Sir2 . +. +, . , + . , . , + , . | 107 | 56. QQ CD38 QQ , . , . CD38 , + , -. , CD38 . CD38 SIRT1, +. , CD38, + . , SIRT1 CD38 SIRT1. , SIRT1 CD38 . , SIRT1 53. (Eduardo N. Chini) (Mayo Clinic), , , , CD38 / + SIRT1, . Sir2 +- , . , Sir2, . Sir2. (Triantafillos Liloglou) (The University of Liverpool, School of Cancer Studies) , .|108|LINE-1 Alu (non-LTR retrotransposons) . LINE-1 Alu 48 . , . , . , . , . , . , Sir2 . Sir2 in vitro (isonicotinamide), Sir2. , Sir2. (Jan M. Willis) (Albert Einstein College of Medicine), -, QQ QQ . Sir2- . (Konrad T. Howitz) (BIOMOL Research Laboratories, Inc) BIOMOL , , . , , . , , , , , , . STAC, , (fisetin) , , . STA (stilbene) 4- . , SIRT1 Saccharomyces cerevisiae. , . STAC (Sirtuin-activating compound) Sir2/SIRT1 NAD+- , , . | 109 | 57. QQ Sir2, , NADQQ , L1 in vivo in vitro. Sir2 . , SIR2 , , , . , Sir2 , . (Leonard Guarente) , (Department of Biology, Massachusetts Institute of Technology), , . : , , . Sir2 NAD, Sir2 NAD- . , , .QQ HDAC , . , , , , . HDAC , .|110| HDAC , , . , . , , . , , . (Yoshiyuki Sakaki) , (Human Genome Center, Institute of Medical Science, University of Tokyo), , , L1, , L1. in vitro , , , (Department of Medical Oncology, Yale Cancer Centre, Yale University), , , L1.QQ HDAC HDAC . . , HDAC , . (William Kevin Kelly) , , , CpGs L1 , .- , . HDAC. , HDAC . HDAC .- , HDAC 24 HDAC . , . . , , , , . , HDAC. .- (De-Maw Chuang) , (Molecular Neurobiology Section, National Institute of Mental Health) , | 111 | 58. QQ HDAC (HDAC) , . (Paul Marks) - (Memorial Sloan-Kettering Cancer Centre), -, .HDACs (SAHA) (). . , , . , , , . - HDAC. , 18 HDAC, 11 . HDAC6 - HDAC , , . , , . HDAC6 . -QQ HDAC Drosophila , , Sir2 Rpd3 C.elegans. , , . .|112| (Frank Slack) , (Yale University), , . , . elegans, . , . , - . , lin-4 lin-14. C. elegans. , . lin-4 lin-14, . , lin-4 lin-14 , , .QQ Sir2, p300 HDAC1 , - , , , . , , - .QQ lin-14 - (Kyung-Tai Min) , (Neurgenetics Branch, National Institute of Health), , . p300/CBP HDAC1. . SKI . . , . , , . (Estela Medrano) (Baylor College of Medicine), , . | 113 | 59. QQ HDAC (Roderick Dashwood) , , , (Department of Environmental and Molecular Toxicology, Linus Pauling Institute, Oregon State University), , . , , () - HDAC . . HDAC HDAC . . , HDAC. , , , . QQ HDAC HDAC. - , HDAC- , , . , HDAC, 53, . , HDAC .|114| , HDAC , () Wnt . , Wnt- -, , Lef/ Tcf . , HDAC /- . , , , . , QQ dTOR , , -TOR, - FOXO. , , . / . (HFD), , . , : ; ISC ISC () ; , 2 , TOR . , dTOR , - , dFOXO. (Sean Oldham) (Burnham Institute for Medical Research), -, . dTOR - . | 115 | 60. QQ JNK- , . JNK- . (Heinrich Jasper) (Department of Biology, University of Rochester), , .QQ c-Jun . , - JunN- (JNK) IGF , . , . , JNK IGF , . . / (IGF), , .QQ - . . ( ) , , - . . . MAPKs ERK ( ), JNK (C-Jun N- ) p38 , , .|116| , , , FGF1, . , MKKK-MKK3/6p38 ASK1-MKK4/7JNK1/2 , , , . , , , - . . (Timothy Chambers) , (Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences), .. , (-67), , C-Jun. , , -67, -Jun .C-Jun -1 , , JNK, , , . . , , , -Jun JNK . , , AP-1- . JNK JNK .QQ MAPKs . (Anthony J. Muslin) (Center for Cardiovascular Research, Washington University School of Medicine), -, . . , , MAP . MAP , . MAPKs , .MAPKs ERK1 / 2 . ERK1 / 2, , -, as- B-RAF, ERK1 / 2 , . ERK1 / 2 . ERK1 / 2 , . , ERK1 / 2 - , . . (Melanie H. Cobb) , - (Department of Pharmacology, The University of Texas Southwestern Medical Center), , | 117 | 61. QQ JNK DAF-16 Caenorhabditis elegans, , C-Jun Nterminal (JNK) DAF-16 . (Heidi Tissenbaum) (University of Massachusetts Medical School), , , JNK1 DAF-16. , , JNK-1 DAF-16 . / , /IGF-1.DAF-16/forkhead , . . , , , JNK-1 DAF-16 .Insulin-like signaling (David Harrison) (The Jackson Laboratory) HSF1 , HSF2, , . .IST-1 JKK-1AGE-1 (Lea Sistonen) (Turku Centre for Biotechnology), .AKT-1/2 JNK-1 P DAF-16DAF-16PStress resistanceLongevity , JNK , DAF-16.|118| : 14% 9%. , TOR , . , TOR .QQ HSF1 HSF2 Environmental cues (Stress, etc.)AAP-1, TOR , , . , TOR , . , TOR . . , JNK signalingDAF-2QQ , HSF1 HSF2 . , , HR-A/B . , , , . , HSF1 HSF2 . , . , 2 HSF1 1 HSF2. , , 2 HSF2 1 HSF1. HSFs. | 119 | 62. QQ HSF1. (Kevin Morano) (University of TexasHouston Medical School), . celastrol, , , HSF1. , HSF1 Saccharomyces cerevisiae ( ) , .QQ thiol reactivityheat shock response antioxidant responsegene expression xenobiotic metabolism and export protein folding and turnovercellular adaptation , . , , . , . , Yap1 , , - - . . (Pope L. Moseley) - (New Mexico State University), , . HSF1 . , Caco-2. , , , 1000 , . HSF1 , HSF1 (. ). HSF1 siRNA . HSF1 Hsp90. , Hsp90 HSF1, . , Hsp90, ( ), ( HSF1) |120| . , .*HSF-1ribosome occludin synthesisoccludin mRNA occludin gene nGAAnnTTCn HSE , HSF1, . 70% . . , Hsp90 50 , . , .occludin HSF-1 (inactive)QQ HSF1 , p53QQ , HSF1 Hsp90 ( 1-2% ).Heat (Ruben Mestril) (The Cardiovascular Institute Loyola University), , . (Hsf) (Hsp). , hsf hsp. , HSF1 , p53. , HSF1 , p53(-/-)., p53(-/-)hsf1(-/-) 8%, . , p53- hsf1(-/-), . (Nahid Mivechi) (Medical College of Georgia), , . . | 121 | 63. QQ HSF1 SIRT1QQ HSF1 - . (Richard I. Morimoto) , , - (Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University), , . (HSFs) - . . C. elegans HSF1 FOXO DAF-16, c . , HSF1 |122| , HSF1 . HSF1 SIRT1 , Sir-2, . : FOXO, p53, nuclear factorB. , , , , , .Aging FOXO, p53, NF BSIRT1 Longevity HSF1 Stress resistance FastingProtein homeostasis SIRT1 , HSF1. , HSF1 SIRT1. . (Susan Lindquist) (Whitehead Institute for Biomedical Research), , . . , . , Hfs1 . (Hsf1+/+) Hsf1 (Hsf1-/-). , . Hsf1-/ , Hsf1+/+. HSF1. HSF1 , Hsp90 , , . , , . , HSF1 HSF1 , , . . | 123 | 64. QQ DAF-16 (FOXO) QQ FOXO 250%, 85%. (Cynthia Kenyon) (Department of Biochemistry and Biophysics, University of California), , ., /IGF1 , FoxOs, . FoxOs , , Caenorhabditis ele . gans . , /IGF1 daf-16. , , FOXO . . , /IGF1. - /IGF1 , , , .QQ FOXO B (PKB/c-akt) .|124| (Department of Biomedical Genetics, University Medical Center Utrecht), , . , / FOXO , , . PI-3 Ras . Ras. , . , , , . FOXO . , FKHR-L1 , . , PKB- FOXO , PI3K/PKB . , , . . . . - . . (Boudewijn M.Th. Burgering) - (PKB) . PKB / FOXO . (Paul Coffer) (Department of Immunology, University Medical Center Utrecht), , . , p70S6 -3 . , AFX, , , . . , , AFX. : FOXO USP7/HAUSP ( - ), FOXO ; Pin1 (, ) FOXO; , - -; , FOXO -1. | 125 | 65. QQ a FOXO (Anne Brunet) (Department of Genetics, Stanford University School of Medicine), , FOXO , (, , ) . , a FOXO , . , , , FOXO . - , : . FOXO SIRT1 , FOXO3: SIRT1 FOXO3 Regulation of FOXO by Sir2 , Extracellular conditions FOXO3 . , Ac , Sir2 Sir2 FOXO Apoptosis FOXO Stress resistance , . Longevity FOXO . . , , FOXO - , , - . . ,|126| QQ IB-alpha NFkB (ROS) , - NFkB- (Msr, Msr). , IB-alpha. NFkB 45 , , (NLS) NFkB. NFkB , , . . , IB-alpha , , , . (Jackob Moskovitz) , , (University of Kansas, School of Pharmacy, Department of Pharmacology and Toxicology) , .QQ STAT3 , . , , . (Irving L. Weissman) , , , (Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine) STAT3, . , STAT3. , , , STAT3, , , . , , STAT3 (, ) . | 127 | 66. QQ NFkB A-42, - -. , A-42 . (Mary Konsolaki) , (State University of New Jersey), . (Paul Schedl) (Princeton University), , . . A-42 . TolI (TI), Tl-NFkB / I (Ilk-1) .QQ 53 NF-kB , , , A-42 , , , . , , TlNFkB A-42. . , Ilk-1-NFkB. , Ilk-1-NFkB - .QQ 53 53 , , . 50% p53. 53. 53 . , , 53, , |128| (). 53 (, PUMA Bcl-2 , in vitro , p53 PUMA . , , Env , gp120. , p53 . (Guido Kroemer) , , . (Apoptosis, cancer and immunity Laboratory, Institut de cancerologie Gustave Roussy), , , , , , , , 53. (Carsten Culmsee) (Institut fr Pharmakologie und Toxikologie, PhilippsUniversitt Marburg), , 53 , , . 53 , 53. 53 , Bax, BH3, PUMA NOXA. , AIF. , 53 Fas up- APAF-1, - , 9. , , , 53 ATM . DNA-PK. , DNA-PK, in vitro in vivo, . 53 - (PFT) , 53 , , , . 53 , 53 NF-kB. 53 , - . 53 . , , NF-kB (bcl-2, bcl-xl, MnSOD, ) (IAPs). p300. 300 , p53 NF-kB . , . 53 - NF-kB , 53. | 129 | 67. QQ 53 , , 53 - .Telomere DysfunctionDS Breaks, Telomere UncappingATM/ATRQQ - CHK2 (Laura Attardi) (Department of Radiation and Cancer Biology, Stanford University), , - 53. 53 . , . . . , ATM- Chk2 , , , . . .p53p21, other?G1 arrestp21, PML, other?Bax, Puma, Noxa, PerpSenescenceApoptosisTUMOR SUPPRESSION53. 53, -. , 53 , G1, . (Matthew Porteus), , - (Department of Pediatrics and Biochemistry, The University of Texas Southwestern Medical Center), , . (ZFN), , . ZFN - . ZFN . 5-18%. Sangamo , - . ZFN I-SceI . , , . ZFN, , . , 100 . ZFNs GFP CD8a . Sangamo Biosciences (Richmond, CA), , 5 , -. , . |130| | 131 | 68. QQ - . . (Robert Lightowlers) , , -- (Mitochondrial Research Group, Institute of Neuroscience, University of Newcastle upon Tyne), , , . , PNAs . PNAs () VIII , , - , , .- (PNAs) , . , PNA , . - , , . , , ( ) ( ). .QQ Nanorex. |132| 340 . . , . - (Adela BenYakar) , (Mechanical Enginee ring Department,The University of Texas at Austin), , . - . - ( 10 15 40 mm) . . (K. Eric Drexler) Nanorex, , (lab on a chip) .elegans . , ( ), , . .QQ NDI1 I. ., , - 10(9) 10(10) amu. , , , , .QQ CCL16-B2 , I, NDI1. NDI1 ( I) . (Saccharomyces cerevisiae), (Ndi1) -10 NDI1 . . (Takao Yagi) , (Department of Molecular and Experimental Medicine, The Scripps Research Institute), , , | 133 | 69. QQ (Mauro Ferrari) , (Department of Nanomedicine and Biomedical Engineering, The University of Texas), , . , . . , , |134| . , . , , . , , . , , , .. in-vitro in-vivo . : (, ). , .QQ , , , . (Rutledge EllisBehnke) , (Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology), , , , , . , , , . 15 . , . , , , in vitro in vivo, . PC12, . , , . , . . | 135 | 70. QQ - , . (Lonnie Shea) - (Department of Chemical and Biological Engineering, Northwestern University), , , , . ( ) . - , in vivo. , 4 . VEGF . , .QQ , , ( ), , . 15-20 . . , (, respirocytes, , , , . , 113 ( ). , , . |136| 4 (Robert Freitas Jr.) (Institute for Molecular Manufacturing IMM), -, 71. , , . , , ( - , ., (, (AGE), .). . . , . , , . , , . , -, . |138| (.. ) -, , -. , , , . - . , , . : 1. . : () . . .2. . 3. . , . , , , . , , , . , . , , , , . , , . , .. , . , , , . , , . , . , , , . . (, , .), , . , . ( ), ( ) ( , ). , . , , ., , ( 196), . . . , 100% . : 1. , . 2. . 3. , . 4. , . 5. . | 139 | 72. QQ LR11 - () . (James J. Lah) (Emory University), , .QQ - . , , . . (Mark S.Kindy) , , (Medical University of South Carolina, ). , , |140| , - . , . . - . , LR11 . . , -.NeuronOligomersNucleusAProtofibrilsSignaling Molecules NeuriteNeuronSynapseAmyloid Plaque Impaired Synapse Neurofibrillary Tangles Axon , , LR11 (c ), - . LR11 , , (presenilin-1) - (APP). , LR11 - , , LR11. PP. , LR11 - in vivo, , . LR11 .QQ AL- AL- ( ) . Blood Vessel () . 2% , . , , , LR11( ), SORLA SORL1. , , . , , AL. , AL-, . (Vaishali Sanchorawala) (Boston University, ), | 141 | 73. QQ - (Serge Rivest) (Laval University) , . , , , . , , , , . . , , -, . . , , , . , . -, , . , , . . , . , . , - . , . , , , . , , in vitro. , . . , , |142| QQ SAP (Philip.N. Hawkins) (National Amyloidosis Centre), UCL (University College of London), , . P (SAP) . - , . SAP , . , SAP , . SAP . , SAP , , , . , SAP . SAP, , . SAP. , , 2.QQ , , , ( ). , . , , . , . . . , , , . , . (Rosie Staniforth) , (Sheffield Uviversity, ). | 143 | 74. QQ QQ , , . Lawreen Connors (Boston University, ). (Cys10) . S- S-. , , , . , . S- S- . , S- , , S-, , . , - .QQ - - , . . APP , . APP. , , , , APP , , (PP), , - , . . , , . , |144| , . , , . . , . , ( , ) . ( 200%). , , . . (Todd Trappe) , , Ball (School of Physical Education, Sport, and Exercise Science at Ball State University), University of Wisconsin), , . (AGE) QQ , . (Agneta Nordberg) , , (Karolinska Unstitute, , ). (). ., , . (Josephine Forbes) , , (Baker Heart Research Institute, Melbourne, Australia) | 145 | 75. QQ , - - . , (Richard Bucala) (Department of Internal Medicine) (Yale University School of Medicine) New Haven , , . (119 ), , (134 ) (234 ). , - , . , , 8- ( ), . , , , , . , , , .QQ , , . , . , , . , |146| . - , , , . . , , . .QQ (Ann Marie Schmidt) (Columbia University Medical Center, Department of Surgery), -, . AGEs ( -, , ). , (AGEs) . AGEs AGEs RAGE, . , AGEs , , , . , RAGE, AGEs, . , RAGE. RAGE , . , -+ RAGE , . AGEs . , , , .QQ (Herv Pageon) (LOral, Centre Charles Zviak, , Clichy Cdex France), , - . , RAGE1. (-), , RAGE1 . , . RAGE1. (Helen Vlassara) , (Mount Sinai Medical Center) -, | 147 | 76. QQ (John W. Baynes) (Dept. of Chemistry and Biochemistry, University of South Carolina), , . , in vitro , , . , 50% , . , HyperglycemiaMicrovascular vasoconstriction, capillary basement membrane thickening, endothelial hyperplasia, hemologic abnormalitiesIncreased extracelluiar protein glycation Increased intracellular glucose in nerve and vascular tissueNeural hypoperfusion and ischemiaRAGE activation Sugar+ROSscarbonylsCarbonyls + proteins or lipids glycoxidation or lipoxidation products . , , , , OPB-9195 . , . N-- . , .AGE formationQQ Increased glycolysis and TCA cycle activityIncreased diacylglycerolRedox reaction: glucose sorbitol fructose (Gerald Mnch) (James Cook University) , , N-.Polyol pathway flux Protein kinase C AGEs (Billy Hudson) (University of Kansas), , .|148| 2,3-, OPB-9195, . AGE . (Dominique Bonnefont-Rousselot - (Universit Paris-Descartes) , QQ B1 6 Protein + glucoseNerve dysfunction and death , . , AGE, , ,Reduced NADPH + glutathione, NADH:NAD+ masbalanceOxidative stress . .QQ Mitochondrial dysfunctionIncreased superoxide , (AGE). AGE in vitro. , , AGE. , , in vitro ( , . ) AGE, , . , B1 6 . . - | 149 | 77. QQ ( ) , , . (Daniel CervantesLaurean) (Chemistry and Biochemistry Department, South Dakota State University) , , . , , . , , . , .QQ , () , . (Sushil K. Jain) (Department of Pediatrics, Louisiana State University Health Sciences Center), , .|150| . AGE , , . .QQ , , , () () ( , 6 ) , . . in vitro . , B6 . , 6 . , 17 5 in vitro. (Bhanuprakash Reddy) (National Institute of Nutrition), , . AGE 40-90% 1.0 /. ., , , in vivo , . .QQ , , . , . , . , , , , . (Carani Venkataraman Anuradha) (Annamalai University) , QQ ( ALT-711) , . (George L.Bakris) , , , . - . . (Rush University), , . | 151 | 78. QQ , QQ - . (Noboru MANABE) (Research Unit for Animal at The University of Tokyo), ., . , . . , - . - , . , , 1.QQ . , .. - ( , ). - 2/3 . , . . - (, ), -|152| , , . . , 2 / , - ( ), , 10 /. -. . , .. , . (Frank Giblin) (Eye Research Institute at Oakland University), , . , , -, (ALL) 2- (2-). , . . . ( ). ALL, 2-. ALL. , 2-AAA , . , . , , , , , 2-AAA. , .QQ . (Robert B. Rucker) (Department of Nutrition) (School of Medicine), (Davis University of California), , , . . , , . , , 30% . . , . 43 15 90 . -, 70-90 , . . (Gitte Ortoft) , (Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus), , . | 153 | 79. QQ () QQ () ? .. , , bw35 . (light-emitting diode (LED) treatments) 660 . , . , 1 31%, MMP-1 18% . , , , , . , - . , . , , . (Daniel Barolet) (McGill University), , .QQ -2 , . . , , . ( , ). , , , (, , ) . , Mg2+ , TIMP-, . Mg2+ . , Mg2+ , , , , Mg2+ ( , ) , . |154| , -2 (-2) . , , -765 - () , -765G. (Francesco Cipollone) (Unit Aging Rsearch Center, G. dAnnunzio University), , . 1728 - . 864 () , 864 . . -765G 43.3% /, 17.9% , 6.4% 1.1%, . , , , , , , , -765G (52%). -765 67%. , -765 -2 . , -765 -2 . - -2 ( -765). | 155 | 80. QQ HGFfibroblast growth factormatrix metalloproteinaseORM1 FOS (Seth Thaller) , (Division of Plastic and Reconstructive Surgery, University of Miami Miller School of Medicine), , .integrinhormone activityIFNGMMP13CXCL12INSJUNcytokine activityCOL2A1 TNFQQ (/) (MMPs) , . In vitro , . (, ) . , , . . . (H. Roger Lijnen) (Center for Molecular and Vascular Biology University of Leuven), , QQ - p53, TIMP1 ), , . , , (Matrix metalloproteinase (MMP)-13). , . , ., , , , . ., - , . , (Matrix metalloproteinase (MMP)-13). -13. , -13 .|156| . - (Carlos Lopez-Otin) (Instituto Universitario de Oncologia del Principado de Asturias (IUOPA)), - , , . ADAMTS (A Disintegrin And Metalloprotease with Thrombospondin domains).- (Degradome) , . - (, LMNA, . , , FACE1/ZMPSTE24. knock-out , , , - p53, . | 157 | 81. QQ (Drew Rowan) (Institute of Cellular Medicine, Medical School, Newcastle University), , .QQ , MMP12 , . MMP8 MMP9 . MMP12 , , , . , , , , . . A (MMP9), (MMP7) , (MMP12), MMP12 . .Cell matrix interactionCytokinese.g. Stromelysin-1 MT-MMPs PlasminActivating enzymes 2 Growth factors (Cawston T.E.) (The Medical School University of Newcastle), , .122ProcollagenasesMechanical stress integrins , , p38 (MAPK), -2 (MMP-2) . MMP-2 . , (Li Xu) . (Raymond C. Bergan) , |158| , -4 (MEK4). MEK4 MMP-2 . MEK4 . 24- , , MMP-2 .1. Synthesissecretion2. Activation , , MMP-2 , . (Lei Xu)Collagen destruction3. Inhibition , , , . , , . , . (Whitaker Biomedical Engineering Institute at Johns Hopkins University School of Medicine), .3TIMPSQQ MMP-2 , , .Active collagenases (MMP-1, -8 -13), , . , . , (OSM) + -1 (IL-1) . MMP-1, -3, -8 -13 ADAM ( ). . , . , , . -39, , , MMPs, , . | 159 | 82. QQ (Ralf Hass) (Medizinische Hochschule Hannover), , - , . -7 20S PARP-1, (primary) , . , . , , , , , . .Oxidative stressDNA, Protein, Lipid damage . . - . - , , . . - . - - . 1 - 22 - 33 Apoptosis in?flation event PARP activeNADONCOSISEnergy changeQQ cFLIP NF-kappaB APOPTOSIS , .PARP INHIBITIONOxidative stressDNA, Protein, Lipid damageApoptosis in?flation event PARP activeodulate PARP activity APOPTOSIS|160| ONCOSIS NF-kappaB . cFLIP ( -8- ), NF-kappaB, . Bcl-xL . , , ( (IL)-1b, TNF- , (PIF)) , , , . . cFLIP, . - (Paula R. Clemens) , (Neurology Service, Pittsburgh VA Healthcare System). | 161 | 83. QQ NFkB . (Leonard M. Neckers) , , (Cell and Cancer Biology Branch, CCR), , - (interleukin-1, IL-1) - HIF-1, , IL-1 HIF1 , . HIF-1- VEGF, QQ NFkB NFkB. IL-1 NFkB- -2 (cyclooxygenase-2, COX-2), , , 2 (prostaglandin E2), - HIF-1. VEGF, . , HIF-1 NFkB , .QQ () , . , , . , . , (Department of Nephrology and Transplantation, Kings College London, England), , . (DC). DC . ( D3) . , , DC . NFkB , - (CD40, CD80 CD86) 3 (ILT3), . , , , NFkB , -, .QQ TNF- - (TRAIL) , () . , , . (Penelope A. Morel) Center for Vaccine Research at the University of Pittsburgh ( , ) - : ; ; - . . -|162| (Giovanna Lombardi) , , , , (APC). , . , , . , (SDF-1), CXCR4 , . ( , ). - , . , TRAIL. , , , , . TRAIL . (Andrew Badley) (MAYO CLINIC), , | 163 | 84. QQ - - : , . . , . , . (Rita Effros) , , (Department of Pathology Laboratory Medicine,David Geffen School of Medicine, University of California Los Angeles UCLA), -, , . , -. , - - , CD3 . , . , , . , - .QQ Foxo3 T- Foxo , . , Foxo3 . . , Foxo3 |164| QQ CD28 (Institute for biomedical aging research), (Karen Arden) - (School of Medicine, University of California San Diego), , CD28 - ? -, NLVPMVATV, , -, , CD8(+)CD28(-) -, CD8(+) CD28(+). , . , CD28 , , CD28 , . .QQ NFkB , (moDC) Simian , NFkB- , . 6. , CTLA-4, Foxo3 . 6 . , Foxo3 . (Beatrix GrubeckLoebenstein) CD28 -. , -. CD28(-) - . , CD28 - - . . NFkB . NFkB- . (, ).Virus 5 (SV5) . . - , TLR-4 -, TLR-6 . , . . (Griffith D. Parks) , (Department of Microbiology and Immunology, Wake Forest University School of Medicine), , . | 165 | 85. QQ - - (Rita Effros) , , (Department of Pathology Laboratory Medicine,David Geffen School of Medicine, University of California Los Angeles UCLA), -, CD8+ - , , , . . , - , , -2 (2) CD8+ - . . , 2 . , , , , , . . , , , . , -QQ (Steven Rosenberg) , (, National Cancer Institute, NCI), . 2002 , IL-2 . 2006 , - , . IL-2 IL -2 . Excise tumourPlate fragmentsReinfuse post-lymphodepletionSelect and expand to 1010 cellsQQ -1 , -1 (IGF-1) . IGF-1 (PAPPA). .|166| PAPPA. IGF-1 - , , . , IGF-1 PAPPA , , .Culture with 6,000 IU/ml IL2 (Abbe N. de Vallejo)Assay for specific tumour recognition -. , IL-2 , . (10^10 ) . (University of Pittsburgh Medical Center, USA), | 167 | 86. QQ , , - (Carl June) , (Medicine School at the University of Pennsylvania), Abramson Cancer Center. , TCR, . -, TCR, 100 (gp100). , , - IL-2. . , - TCR . , ,