Administration with Bushenkangshuai Tang alleviates UV irradiation- and oxidative stress-induced lifespan defects in nematode Caenorhabditis elegans

Abstract

During normal metabolism, oxidative byproducts will inevitably generate and damage molecules thereby impairing their biological functions, including the aging process. Bushenkangshuai Tang (补肾抗衰方, BT) is a traditional Chinese medicine widely used for clinically treating premature ovarian failure. In the present study, BT administration at high concentrations significantly increased lifespan, slowed aging-related decline, and delayed accumulation of aging-related cellular damage in wild-type Caenorhabditis elegans. BT administration could further largely alleviate the aging defects induced by UV and oxidative stresses, and BT administration at different concentrations could largely rescue the aging defects in mev-1 mutant animals. The protective effects of BT administration on aging process were at least partially dependent on the Ins/IGF-like signaling pathway. Moreover, BT administration at different concentrations obviously altered the expression patterns of antioxidant genes and suppressed the severe stress responses induced by UV and oxidative stresses, suggesting that BT-induced tolerance to UV or oxidative stress might result from reactive oxygen species scavenging. BT administration during development was not necessarily a requirement for UV and oxidative stress resistance, and the concentrations of administrated BT examined were not toxic for nematodes. Therefore, BT administration could effectively retrieve the aging defects induced by UV irradiation and oxidative stress in Caenorhabditis elegans.

Key words： Bushenkangshuai Tang; UV irradiation; oxidative stress; tissue senescence; lifespan; Caenorhabditis elegans

Acknowledgements

Strains used in this work were provided by the Caenorhabdits Genetics Center (funded by the National Institutes of Health, National Center for Foundation from Research Resource). This work was supported by the grants from the National Natural Science Foundation of China (Grant No. 30771113), the Program for New Century Excellent Talents in University, and the Nanjing Scientific and Technical Plan (No. 200701113).

References

1 KlassM R. Aging in nematode Caenorhabditis elegans — major biological and environmental-factors influencing life-span. Mech Ageing Dev, 1977, 6(6): 413-429

2 BraeckmanB P, VanfleterenJ R. Genetic control of longevity in C. elegans. Exp Gerontol, 2007, 42(1-2): 90-98

3 ShenL L, WangY, WangD Y. Involvement of genes required for synaptic function in aging control in C. elegans. Neurosci Bull, 2007, 23(1): 21-29

4 KenyonC, ChangJ, GenschE, RudnerA, TabtiangR A. C. elegans mutant that lives twice as long as wild-type. Nature, 1993, 366(6454): 461-464

5 KimuraK D, TissenbaumH A, LiuY, RuvkunG. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science, 1997, 277(5328): 942-946

6 LinK, HsinH, LibinaN, KenyonC. Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet, 2001, 28(2): 139-145

7 HarmanD. Aging: a theory based on free radical and radiation chemistry. J Gerontol, 1956, 11(3): 298-300

8 SampayoJ N, OlsenA, LithgowG J. Oxidative stress in Caenorhabditis elegans: protective effects of superoxide dismutase/catalase mimetics. Aging Cell, 2003, 2(6): 319-326

9 BrysK, VanfleterenJ R, BraeckmanB P. Testing the rate-of-living/oxidative damage theory of aging in the nematode model Caenorhabditis elegans. Exp Gerontol, 2007, 42(9): 845-851

10 BeckmanK B, AmesB N. The free radical theory of aging matures. Physiol Rev, 1998, 78(2): 547-581

11 FinkelT, HolbrookN J. Oxidants, oxidative stress and the biology of ageing. Nature, 2000, 408(6809): 239-247

12 LarsenP L. Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA, 1993, 90(19): 8905-8909

13 VanfleterenJ R. Oxidative stress and ageing in Caenorhabditis elegans. Biochem J, 1993, 292(Pt. 2): 605-608

14 IshiiN, FujiiM, HartmanP S, TsudaM, YasudaK, Senoo-MatsudaN, YanaseS, AyusawaD, SuzukiK. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature, 1998, 394(6694): 694-697

15 LithgowG J, WhiteT M, MelovS, JohnsonT E. Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci USA, 1995, 92(16): 7540-7544

16 MurakamiS, JohnsonT E. A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics, 1996, 143(3): 1207-1218

17 BarsyteD, LovejoyD A, LithgowG J. Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of Caenorhabditis elegans. FASEB J, 2001, 15(3): 627-634

18 LithgowG J, WalkerG A. Stress resistance as a determinate of C. elegans lifespan. Mech Ageing Dev, 2002, 123(7): 765-771

19 HarringtonL A, HarleyC B. Effects of vitamin E on lifespan and reproduction in Caenorhabditis elegans. Mech Ageing Dev, 1988, 43(11): 71-78

20 IshiiN, Senoo-MatsudaN, MiyakeK, YasudaK, IshiiT, HartmanP S, FurakawaS. Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress. Mech Ageing Dev, 2004, 125(1): 41-46

21 JonassenT, LarsenP L, ClarkeC F. A dietary source of coenzyme Q is essential for growth of long-lived Caenorhabditis elegans clk-1 mutants. Proc Natl Acad Sci USA, 2001, 98(2): 421-426

22 WuZ, SmithJ V, ParamasivamV, ButkoP, KhanL, CypserJ R, LuoY. Ginkgo biloba extract EGb 761 increases stress resistance and extends lifespan of Caenorhabditis elegans. Cell Mol Biol, 2002, 48(6): 725-731

23 LinY T, HoangH, HsiehS, RangelN, FosterA L, SampayoJ N, LithgowG J, SrinivasanC. Manganous ion supplementation accelerates wild type development, enhances stress resistance, and rescues the life span of a short-lived Caenorhabditis elegans mutant. Free Radical Biol Med, 2006, 40(7): 1185-1193

24 GoswamiD, ConwayG S. Premature ovarian failure. Hum Reprod Update, 2005, 11(4): 391-410

25 PalL, SantoroN. Premature ovarian failure (POF): discordance between somatic and reproductive aging. Ageing Res Rev, 2002, 1(3): 413-423

26 HuX M, RobertsJ R, ApopaP L, KanY W, MaQ. Accelerated ovarian failure induced by 4-vinyl cyclohexene diepoxide in Nrf2 null mice. Mol Cell Biol, 2006, 26(3): 940-954

27 GraziewiczM A, BienstockR J, CopelandW C. The DNA polymerase γ Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite7, 8-dihydro-8-oxo-2’-deoxyguanosine. Hum Mol Genet, 2007, 16(22): 2729-2739

28 BrennerS. The genetics of Caenorhabditis elegans. Genetics, 1974, 77(1): 71-94

29 DonkinS G, WilliamsP L. Influence of developmental stage, salts and food presence on various end points using Caenorhabditis elegans for aquatic toxicity testing. Environ Toxicol Chem, 1995, 14(12): 2139-2147

30 WilliamsP L, DusenberyD B. Aquatic toxicity testing using the nematode Caenorhabditis elegans. Environ Toxicol Chem, 1990, 9(10): 1285-1290

31 YeH Y, YeB P, WangD Y. Trace administration of vitamin E can retrieve and prevent UV-irradiation- and metal exposure-induced memory deficits in nematode Caenorhabditis elegans. Neurobiol Learn Mem, 2008, 90(1): 10-18

32 WilsonM A, Shukitt-HaleB, KaltW, IngramD K, JosephJ A, WolkowC A. Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell, 2006, 5(1): 59-68

33 WangY, XieW, WangD Y. Transferable properties of multi-biological toxicity caused by cobalt exposure in Caenorhabditis elegans. Environ Toxicol Chem, 2007, 26(11): 2405-2412

34 HuangC, XiongC, KornfeldK. Measurements of age-related changes of physiological processes that predict lifespan of Caenorhabditis elegans. Proc Natl Acad Sci USA, 2004, 101(21): 8084-8089

35 WangD Y, WangY. Phenotypic and behavioral defects caused by barium exposure in nematode Caenorhabditis elegans. Arch Environ Contam Toxicol, 2008, 54(3): 447-453

36 YanaseS, IshiiN. Cloning of the oxidative stress-responsive genes in Caenorhabditis elegans. J Rad Res, 1999, 40(1): 39-47

37 MorseD P, BassB L. Long RNA hairpins that contain inosine are present in Caenorhabditis elegans poly(A)⁺ RNA. Proc Natl Acad Sci USA, 1999, 96(11): 6048-6053

38 GemsD, SuttonA J, SundermeyerM L, AlbertP S, KingK V, EddleyM L, LarsenP L, RiddleD L. Two pleiotropic classes of daf-2 mutations affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics, 1998, 150(1): 129-155

39 BrunkU, TermanA. Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Free Radic Biol Med, 2002, 33(5): 611-619

40 YanaseS, YasudaK, IshiiN. Adaptive responses to oxidative damage in three mutants of Caenorhabditis elegans (age-1, mev-1and daf-16) that affect life span. Mech Ageing Dev, 2002, 123(12): 1579-1587

41 OttolenghiC, UdaM, HamataniT, CrisponiL, GarciaJ E, KoM, PiliaG, SforzaC, SchlessingerD, ForaboscoA. Aging of oocyte, ovary, and human reproduction. Ann N Y Acad Sci, 2004, 1034: 117-131

42 RichardsonS J, SenkiasV, NelsonJ F. Follicular depletion during menopausal transition: evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab, 1987, 65(6): 1231-1237

43 SnowdownD A, KaneR L, BeesonW L, BurkeG L, SprafkaJ M, PotterJ, IsoH, JacobsD R Jr, PhillipsR L. Is early natural menopause a biological marker of health and aging? Am J Public Health, 1989, 79(6): 709-714

44 AnastiJ N. Premature ovarian failure: an update. Fertil Steril, 1998, 70(1): 1-15

45 BrambillaD J, McKinleyS M. A prospective study of factors affecting age at menopause. J Clin Epidemiol, 1989, 42(11): 1031-1039

46 HolzenbergerM, DupontJ, DucosB, LeneuveP, GéloënA, EvenP C, CerveraP, BoucY L. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature, 2003, 421(6919): 182-186

47 WiseP M. Neuroendocrine modulation of the menopause: insights into the aging brain. Am J Physiol (Endocrinol Metab), 1999, 40(6): E965-970

48 YangW, LiJ, HekimiS. A measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans. Genetics, 2007, 177(4): 2063-2074

49 CastrillonD H, MiaoL, KolliparaR, HornerJ W, DePinhoR A. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science, 2003, 301(5630): 215-217

50 BayneA C, SohalR S. Effects of superoxide dismutase/catalase mimetics on life span and oxidative stress resistance in the housefly, Musca domestica. Free Radic Biol Med, 2002, 32(11): 1229-1234

51 KeaneyM, GemsD. No increase in lifespan in Caenorhabditis elegans upon treatment with the superoxide dismutase mimetic Euk-8. Free Radic Biol Med, 2003, 34(2): 277-282

52 HulleyS, GradyD, BushT, FurbergC, HerringtonD, RiggsB, VittinghoffE. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA, 1998, 280(7): 605-613

53 Letur-KonirschH, DelanianS. Successful pregnancies after combined pentoxifylline-tocopherol treatment in women with premature ovarian failure who are resistant to hormone replacement therapy. Fertil Steril, 2003, 79(2): 439-441