Modulators of cellular senescence: Mechanisms, promises, and challenges from in vitro studies with dietary bioactive compounds

Nutrition Research

Volumn 34, Issue 12, 2014, Pages 1017-1035

  Malavolta, Marco ^a   Costarelli, Laura ^a   Giacconi, Robertina ^a   Piacenza, Francesco ^a   Basso, Andrea ^a   Pierpaoli, Elisa ^b   Marchegiani, Francesca ^b   Cardelli, Maurizio ^b   Provinciali, Mauro ^b   Mocchegiani, Eugenio ^a  

^a Italian National Institute of Health and Science on Aging   (United States)

^b Italian National Institute of Health and Science on Ageing (INRCA)   (Italy)

Author keywords

Aging; Bioactive dietary compounds; Cancer; Cellular senescence; Senescence modulators

Indexed keywords

ALPHA TOCOTRIENOL; APIGENIN; ASCORBIC ACID; BERBERINE; CARNOSINE; CATECHIN; CORTICOSTERONE; CURCUMIN; EPIGALLOCATECHIN GALLATE; GINSENOSIDE; GLUCOSAMINE; HYDROCORTISONE; LENALIDOMIDE; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; METFORMIN; MORIN; NATURAL PRODUCT; PENTA 1,2,3,4,6 O GALLOYL BETA GLUCOSE; PHLORETIN; POLYPHENOL; PYRITHIONE ZINC; QUERCETIN; REACTIVE OXYGEN METABOLITE; RESVERATROL; TA 65; TANNIN; TELOMERASE; TETRAPYRROLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; PLANT EXTRACT;

AGING; CANCER CELL; CELL AGING; CELL CYCLE ARREST; CELL FUNCTION; CELLS BY BODY ANATOMY; CELLULAR PARAMETERS; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME REGULATION; EPIGENETICS; GEROCONVERSION; HUMAN; IMMUNOSURVEILLANCE; IN VITRO STUDY; NONHUMAN; PRIMARY CELL; REVIEW; SENESCENCE ASSOCIATED SECRETORY PHENOTYPE; SENESCENT CELL; SIGNAL TRANSDUCTION; STRESS INDUCED PREMATURE SENESCENCE; TARGET CELL; DIET; DRUG EFFECTS; NEOPLASMS;

AGING; CELL AGING; DIET; HUMANS; NEOPLASMS; PLANT EXTRACTS; POLYPHENOLS;

EID: 84919497725     PISSN: 02715317     EISSN: 18790739     Source Type: Journal    
DOI: 10.1016/j.nutres.2014.02.006     Document Type: Review

References (198)

1. Kuilman T., Michaloglou C., Mooi W.J., Peeper D.S. The essence of senescence. Genes Dev 2010, 24:2463-2479.
2. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol 2013, 75:685-705.
3. Argyropoulou A., Aligiannis N., Trougakos I.P., Skaltsounis A.L. Natural compounds with anti-ageing activity. Nat Prod Rep 2013, 30:1412-1437. [Oct 11].
4. Hayflick L., Moorhead P.S. The serial cultivation of human diploid cell strains. Exp Cell Res 1961, 25:585-621.
5. Counter C.M., Meyerson M., Eaton E.N., Ellisen L.W., Caddle S.D., Haber D.A., et al. Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase. Oncogene 1998, 16:1217-1222. [Mar 5].
6. Chen Q., Fischer A., Reagan J.D., Yan L.J., Ames B.N. Oxidative DNA damage and senescence of human diploid fibroblast cells. Proc Natl Acad Sci U S A 1995, 92:4337-4341. [May 9].
7. Brack C., Lithgow G., Osiewacz H., Toussaint O. EMBO Workshop report: molecular and cellular gerontology Serpiano, Switzerland, September 18-22, 1999. EMBO J 2000, 19:1929-1934. [May 2].
8. Gorbunova V., Seluanov A., Pereira-Smith O.M. Expression of human telomerase (hTERT) does not prevent stress-induced senescence in normal human fibroblasts but protects the cells from stress-induced apoptosis and necrosis. J Biol Chem 2002, 277:38540-38549. [Oct 11].
9. Wei S., Wei S., Sedivy J.M. Expression of catalytically active telomerase does not prevent premature senescence caused by overexpression of oncogenic Ha-Ras in normal human fibroblasts. Cancer Res 1999, 59:1539-1543. [Apr 1].
10. Serrano M., Lin A.W., McCurrach M.E., Beach D., Lowe S.W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997, 88:593-602. [Mar 7].
11. Bianchi-Smiraglia A., Nikiforov M.A. Controversial aspects of oncogene-induced senescence. Cell Cycle 2012, 11:4147-4151.
12. Sulli G., Di Micco R., D'Adda Di Fagagna F. Crosstalk between chromatin state and DNA damage response in cellular senescence and cancer. Nat Rev Cancer 2012, 12:709-720. [Oct, Epub 2012 Sep 6]. 10.1038/nrc3344.
13. de Lange T. Telomere-related genome instability in cancer. Cold Spring Harb Symp Quant Biol 2005, 70:197-204.
14. Shamma A., Takegami Y., Miki T., Kitajima S., Noda M., Obara T., et al. Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation. Cancer Cell 2009, 15:255-269. [Apr 7].
15. Collado M., Blasco M.A., Serrano M. Cellular senescence in cancer and aging. Cell 2007, 130:223-233.
16. Hasty P., Sharp Z.D., Curiel T.J., Campisi J. mTORC1 and p53: clash of the gods?. Cell Cycle 2013, 12:20-25.
17. Korotchkina L.G., Leontieva O.V., Bukreeva E.I., Demidenko Z.N., Gudkov A.V., Blagosklonny M.V. The choice between p53-induced senescence and quiescence is determined in part by the mTOR pathway. Aging (Albany NY) 2010, 2:344-352.
18. Wall M., Poortinga G., Stanley K.L., Lindemann R.K., Bots M., Chan C.J., et al. The mTORC1 inhibitor everolimus prevents and treats Eμ-Myc lymphoma by restoring oncogene-induced senescence. Cancer Discov 2013, 3:82-95.
19. Nam H.Y., Han M.W., Chang H.W., Kim S.Y., Kim S.W. Prolonged autophagy by MTOR inhibitor leads radioresistant cancer cells into senescence. Autophagy 2013, 9:1631-1632.
20. Young A.R., Narita M., Ferreira M., Kirschner K., Sadaie M., Darot J.F., et al. Autophagy mediates the mitotic senescence transition. Genes Dev 2009, 23:798-803.
21. de Jesus B.B., Blasco M.A. Assessing cell and organ senescence biomarkers. Circ Res 2012, 111:97-109.
22. Jeyapalan J.C., Sedivy J.M. Cellular senescence and organismal aging. Mech Ageing Dev 2008, 129:467-474.
23. Ogrunc M., D'Adda Di Fagagna F. Never-ageing cellular senescence. Eur J Cancer 2011, 47:1616-1622.
24. Muñoz-Espín D., Cañamero M., Maraver A., Gómez-López G., Contreras J., Murillo-Cuesta S., et al. Programmed cell senescence during mammalian embryonic development. Cell 2013, 155:1104-1118.
25. Krizhanovsky V., Yon M., Dickins R.A., Hearn S., Simon J., Miething C., et al. Senescence of activated stellate cells limits liver fibrosis. Cell 2008, 134:657-667. [Aug 22].
26. Coppé J.P., Patil C.K., Rodier F., Sun Y., Muñoz D.P., Goldstein J., et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008, 6:2853-2868. [Dec 2]. 10.1371/journal.pbio.0060301.
27. Acosta J.C., Banito A., Wuestefeld T., Georgilis A., Janich P., Morton J.P., et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 2013, 15:978-990. [Aug]. 10.1038/ncb2784.
28. Naylor R.M., Baker D.J., van Deursen J.M. Senescent cells: a novel therapeutic target for aging and age-related diseases. Clin Pharmacol Ther 2013, 93:105-116.
29. Hampel B., Wagner M., Teis D., Zwerschke W., Huber L.A., Jansen-Dürr P. Apoptosis resistance of senescent human fibroblasts is correlated with the absence of nuclear IGFBP-3. Aging Cell 2005, 4:325-330.
30. Baker D.J., Wijshake T., Tchkonia T., LeBrasseur N.K., Childs B.G., van de Sluis B., et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011, 479:232-236. [Nov 2]. 10.1038/nature10600.
31. Blagosklonny M.V. Cell cycle arrest is not yet senescence, which is not just cell cycle arrest: terminology for TOR-driven aging. Aging (Albany NY) 2012, 4:159-165.
32. Lapasset L., Milhavet O., Prieur A., Besnard E., Babled A., Aït-Hamou N., et al. Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev 2011, 25:2248-2253.
33. Beauséjour C.M., Krtolica A., Galimi F., Narita M., Lowe S.W., Yaswen P., et al. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 2003, 22:4212-4222. [Aug 15].
34. Pospelova T.V., Leontieva O.V., Bykova T.V., Zubova S.G., Pospelov V.A., Blagosklonny M.V. Suppression of replicative senescence by rapamycin in rodent embryonic cells. Cell Cycle 2012, 11:2402-2407.
35. Kolesnichenko M., Hong L., Liao R., Vogt P.K., Sun P. Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced senescence. Cell Cycle 2012, 11:2391-2401.
36. McFarland G.A., Holliday R. Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res 1994, 212:167-175.
37. McFarland G., Holliday R. Differential response of embryonic stem cells and teratocarcinoma cells to carnosine. In Vitro Cell Dev Biol Anim 1999, 35:15-16.
38. Chondrogianni N., Kapeta S., Chinou I., Vassilatou K., Papassideri I., Gonos E.S. Anti-ageing and rejuvenating effects of quercetin. Exp Gerontol 2010, 45:763-771.
39. Makpol S., Durani L.W., Chua K.H., Mohd Yusof Y.A., Ngah W.Z. Tocotrienol-rich fraction prevents cell cycle arrest and elongates telomere length in senescent human diploid fibroblasts. J Biomed Biotechnol 2011, 2011:506171.
40. Hoenicke L., Zender L. Immune surveillance of senescent cells-biological significance in cancer- and non-cancer pathologies. Carcinogenesis 2012, 33:1123-1126.
41. Laberge R.M., Adler D., DeMaria M., Mechtouf N., Teachenor R., Cardin G.B., et al. Mitochondrial DNA damage induces apoptosis in senescent cells. Cell Death Dis 2013, 4:e727.
42. Cerella C., Michiels C., Dashwood R.H., Surh Y.J., Diederich M. Metabolism and cancer: old and new players. Int J Cell Biol 2013, 2013:293201. 10.1155/2013/293201.
43. Dörr J.R., Yu Y., Milanovic M., Beuster G., Zasada C., Däbritz J.H., et al. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature 2013, 501:421-425.
44. Torres M.P., Rachagani S., Purohit V., Pandey P., Joshi S., Moore E.D., et al. Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer Lett 2012, 323:29-40.
45. Huang M.C., Greig N.H., Luo W., Tweedie D., Schwartz J.B., Longo D.L., et al. Preferential enhancement of older human T cell cytokine generation, chemotaxis, proliferation and survival by lenalidomide. Clin Immunol 2011, 138:201-211.
46. Dasanu C.A., Mitsis D., Alexandrescu D.T. Hair repigmentation associated with the use of lenalidomide: graying may not be an irreversible process!. J Oncol Pharm Pract 2013, 19:165-169.
47. Mocchegiani E., Romeo J., Malavolta M., Costarelli L., Giacconi R., Diaz L.E., et al. Zinc: dietary intake and impact of supplementation on immune function in elderly. Age (Dordr) 2013, 35:839-860.
48. Moiseeva O., Deschênes-Simard X., Pollak M., Ferbeyre G. Metformin, aging and cancer. Aging (Albany NY) 2013, 5:330-331.
49. Menendez J.A., Cufí S., Oliveras-Ferraros C., Martin-Castillo B., Joven J., Vellon L., et al. Metformin and the ATM DNA damage response (DDR): accelerating the onset of stress-induced senescence to boost protection against cancer. Aging (Albany NY) 2011, 3:1063-1077.
50. Kang T.W., Yevsa T., Woller N., Hoenicke L., Wuestefeld T., Dauch D., et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 2011, 479:547-551.
51. Laberge R.M., Zhou L., Sarantos M.R., Rodier F., Freund A., de Keizer P.L., et al. Glucocorticoids suppress selected components of the senescence-associated secretory phenotype. Aging Cell 2012, 11:569-578.
52. Lopez H.L. Nutritional interventions to prevent and treat osteoarthritis. Part II: focus on micronutrients and supportive nutraceuticals. PM R 2012, 4:S155-S168.
53. Imagawa K., de Andrés M.C., Hashimoto K., Pitt D., Itoi E., Goldring M.B., et al. The epigenetic effect of glucosamine and a nuclear factor-kappa B (NF-kB) inhibitor on primary human chondrocytes-implications for osteoarthritis. Biochem Biophys Res Commun 2011, 405:362-367.
54. Brasky T.M., Lampe J.W., Slatore C.G., White E. Use of glucosamine and chondroitin and lung cancer risk in the VITamins And Lifestyle (VITAL) cohort. Cancer Causes Control 2011, 22:1333-1342.
55. Pocobelli G., Kristal A.R., Patterson R.E., Potter J.D., Lampe J.W., Kolar A., et al. Total mortality risk in relation to use of less-common dietary supplements. Am J Clin Nutr 2010, 91:1791-1800.
56. Hardie D.G. Sensing of energy and nutrients by AMP-activated protein kinase. Am J Clin Nutr 2011, 93:891S-896S.
57. Moghadam-Kia S., Werth V.P. Prevention and treatment of systemic glucocorticoid side effects. Int J Dermatol 2010, 49:239-248.
58. Xue W., Zender L., Miething C., Dickins R.A., Hernando E., Krizhanovsky V., et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007, 445:656-660.
59. Nardella C., Clohessy J.G., Alimonti A., Pandolfi P.P. Pro-senescence therapy for cancer treatment. Nat Rev Cancer 2011, 11:503-511.
60. Naasani I., Seimiya H., Tsuruo T. Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins. Biochem Biophys Res Commun 1998, 249:391-396.
61. Berletch J.B., Liu C., Love W.K., Andrews L.G., Katiyar S.K., Tollefsbol T.O. Epigenetic and genetic mechanisms contribute to telomerase inhibition by EGCG. J Cell Biochem 2008, 103:509-519.
62. Ramachandran C., Fonseca H.B., Jhabvala P., Escalon E.A., Melnick S.J. Curcumin inhibits telomerase activity through human telomerase reverse transcritpase in MCF-7 breast cancer cell line. Cancer Lett 2002, 184:1-6.
63. Eitsuka T., Nakagawa K., Miyazawa T. Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol. Biochem Biophys Res Commun 2006, 348:170-175.
64. Gui C.Y., Ngo L., Xu W.S., Richon V.M., Marks P.A. Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. Proc Natl Acad Sci U S A 2004, 101:1241-1246.
65. Pierpaoli E., Viola V., Pilolli F., Piroddi M., Galli F., Provinciali M. Gamma- and delta-tocotrienols exert a more potent anticancer effect than alpha-tocopheryl succinate on breast cancer cell lines irrespective of HER-2/neu expression. Life Sci 2010, 86:668-675.
66. Pierpaoli E., Viola V., Barucca A., Orlando F., Galli F., Provinciali M. Effect of annatto-tocotrienols supplementation on the development of mammary tumors in HER-2/neu transgenic mice. Carcinogenesis 2013, 34:1352-1360.
67. Moon D.O., Kang S.H., Kim K.C., Kim M.O., Choi Y.H., Kim G.Y. Sulforaphane decreases viability and telomerase activity in hepatocellular carcinoma Hep3B cells through the reactive oxygen species-dependent pathway. Cancer Lett 2010, 295:260-266.
68. Jayasooriya R.G., Kang S.H., Kang C.H., Choi Y.H., Moon D.O., Hyun J.W., et al. Apigenin decreases cell viability and telomerase activity in human leukemia cell lines. Food Chem Toxicol 2012, 50:2605-2611.
69. Thakur V.S., Gupta K., Gupta S. Green tea polyphenols increase p53 transcriptional activity and acetylation by suppressing class I histone deacetylases. Int J Oncol 2012, 41:353-361.
70. Nandakumar V., Vaid M., Katiyar S.K. (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes, Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells. Carcinogenesis 2011, 32:537-544.
71. Ahmad N., Adhami V.M., Gupta S., Cheng P., Mukhtar H. Role of the retinoblastoma (pRb)-E2F/DP pathway in cancer chemopreventive effects of green tea polyphenol epigallocatechin-3-gallate. Arch Biochem Biophys 2002, 398:125-131.
72. Huang J., Plass C., Gerhauser C. Cancer chemoprevention by targeting the epigenome. Curr Drug Targets 2011, 12:1925-1956.
73. Lançon A., Michaille J.J., Latruffe N. Effects of dietary phytophenols on the expression of microRNAs involved in mammalian cell homeostasis. J Sci Food Agric 2013, 93:3155-3164.
74. Kauntz H., Bousserouel S., Gossé F., Raul F. Epigenetic effects of the natural flavonolignan silibinin on colon adenocarcinoma cells and their derived metastatic cells. Oncol Lett 2013, 5:1273-1277.
75. Provinciali M., Papalini F., Orlando F., Pierpaoli S., Donnini A., Morazzoni P., et al. Effect of the silybin-phosphatidylcholine complex (IdB1016) on the development of mammary tumors in HER-2/neu transgenic mice. Cancer Res 2007, 67:2022-2029.
76. Lee W.J., Chen Y.R., Tseng T.H. Quercetin induces FasL-related apoptosis, in part, through promotion of histone H3 acetylation in human leukemia HL-60 cells. Oncol Rep 2011, 25:583-591.
77. Majid S., Kikuno N., Nelles J., Noonan E., Tanaka Y., Kawamoto K., et al. Genistein induces the p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms involving active chromatin modification. Cancer Res 2008, 68:2736-2744.
78. Silvers A.L., Lin L., Bass A.J., Chen G., Wang Z., Thomas D.G., et al. Decreased selenium-binding protein 1 in esophageal adenocarcinoma results from posttranscriptional and epigenetic regulation and affects chemosensitivity. Clin Cancer Res 2010, 16:2009-2021.
79. Kai L., Samuel S.K., Levenson A.S. Resveratrol enhances p53 acetylation and apoptosis in prostate cancer by inhibiting MTA1/NuRD complex. Int J Cancer 2010, 126:1538-1548.
80. Rusin M., Zajkowicz A., Butkiewicz D. Resveratrol induces senescence-like growth inhibition of U-2 OS cells associated with the instability of telomeric DNA and upregulation of BRCA1. Mech Ageing Dev 2009, 130:528-537.
81. Provinciali M., Cardelli M., Marchegiani F., Pierpaoli E. Impact of cellular senescence in aging and cancer. Curr Pharm Des 2013, 19:1699-1709.
82. Rajendran P., Ho E., Williams D.E., Dashwood R.H. Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells. Clin Epigenetics 2011, 3:4.
83. Shi Y., Frankel A., Radvanyi L.G., Penn L.Z., Miller R.G., Mills G.B. Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro. Cancer Res 1995, 55(9):1982-1988. [May 1].
84. Zhang X., Li X.R., Zhang J. Current status and future perspectives of PI3K and mTOR inhibitor as anticancer drugs in breast cancer. Curr Cancer Drug Targets 2013, 13:175-187.
85. Easton J.B., Houghton P.J. mTOR and cancer therapy. Oncogene 2006, 25:6436-6446.
86. Pópulo H., Lopes J.M., Soares P. The mTOR signalling pathway in human cancer. Int J Mol Sci 2012, 13:1886-1918.
87. Choi Y.K., Park K.G. Metabolic roles of AMPK and metformin in cancer cells. Mol Cells 2013, 36:279-287.
88. Saini K.S., Loi S., de Azambuja E., Metzger-Filho O., Saini M.L., Ignatiadis M., et al. Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat Rev 2013, 39:935-946.
89. Adhami V.M., Syed D.N., Khan N., Mukhtar H. Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management. Biochem Pharmacol 2012, 84:1277-1281.
90. Syed D.N., Adhami V.M., Khan M.I., Mukhtar H. Inhibition of Akt/mTOR signaling by the dietary flavonoid fisetin. Anticancer Agents Med Chem 2013, 13:995-1001.
91. Puissant A., Auberger P. AMPK- and p62/SQSTM1-dependent autophagy mediate resveratrol-induced cell death in chronic myelogenous leukemia. Autophagy 2010, 6:655-657.
92. Pan W., Yang H., Cao C., Song X., Wallin B., Kivlin R., et al. AMPK mediates curcumin-induced cell death in CaOV3 ovarian cancer cells. Oncol Rep. 2008;20:1553-9; Lee YK, Park SY, Kim YM, Park OJ. Regulatory effect of the AMPK-COX-2 signaling pathway in curcumin-induced apoptosis in HT-29 colon cancer cells. Ann N Y Acad Sci 2009, 1171:489-494.
93. Beevers C.S., Chen L., Liu L., Luo Y., Webster N.J., Huang S. Curcumin disrupts the Mammalian target of rapamycin-raptor complex. Cancer Res 2009, 69:1000-1008.
94. Mosieniak G., Adamowicz M., Alster O., Jaskowiak H., Szczepankiewicz A.A., Wilczynski G.M., et al. Curcumin induces permanent growth arrest of human colon cancer cells: link between senescence and autophagy. Mech Ageing Dev 2012, 133:444-455.
95. Huang C.H., Tsai S.J., Wang Y.J., Pan M.H., Kao J.Y., Way T.D. EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells. Mol Nutr Food Res 2009, 53:1156-1165.
96. Zhao H., Halicka H.D., Li J., Darzynkiewicz Z. Berberine suppresses gero-conversion from cell cycle arrest to senescence. Aging (Albany NY) 2013, 5:623-636.
97. Pierpaoli E., Arcamone A.G., Buzzetti F., Lombardi P., Salvatore C., Provinciali M. Antitumor effect of novel berberine derivatives in breast cancer cells. Biofactors 2013, 39:672-679.
98. Babich H., Schuck A.G., Weisburg J.H., Zuckerbraun H.L. Research strategies in the study of the pro-oxidant nature of polyphenol nutraceuticals. J Toxicol 2011, 2011:467305.
99. Luo H., Yang A., Schulte B.A., Wargovich M.J., Wang G.Y. Resveratrol induces premature senescence in lung cancer cells via ROS-mediated DNA damage. PLoS One 2013, 8:e60065.
100. Yin S., Dong Y., Li J., Lü J., Hu H. Penta-1,2,3,4,6-O-galloyl-beta-d-glucose induces senescence-like terminal S-phase arrest in human hepatoma and breast cancer cells. Mol Carcinog 2011, 50:592-600.
101. Ewald J.A., Peters N., Desotelle J.A., Hoffmann F.M., Jarrard D.F. A high-throughput method to identify novel senescence-inducing compounds. J Biomol Screen 2009, 14:853-858.
102. Patrushev N., Seidel-Rogol B., Salazar G. Angiotensin II requires zinc and downregulation of the zinc transporters ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells. PLoS One 2012, 7:e33211.
103. Rudolf E., Cervinka M. Stress responses of human dermal fibroblasts exposed to zinc pyrithione. Toxicol Lett 2011, 204:164-173.
104. Li Y., Hu J., Guan F., Song L., Fan R., Zhu H., et al. Copper induces cellular senescence in human glioblastoma multiforme cells through downregulation of Bmi-1. Oncol Rep 2013, 29:1805-1810.
105. Wu M., Kang M.M., Schoene N.W., Cheng W.H. Selenium compounds activate early barriers of tumorigenesis. J Biol Chem 2010, 285:12055-12062.
106. Mocchegiani E., Giacconi R., Malavolta M. Zinc signalling and subcellular distribution: emerging targets in type 2 diabetes. Trends Mol Med 2008, 14:419-428.
107. Namdarghanbari M., Wobig W., Krezoski S., Tabatabai N.M., Petering D.H. Mammalian metallothionein in toxicology, cancer, and cancer chemotherapy. J Biol Inorg Chem 2011, 16:1087-1101.
108. Yang J., Zhang Y., Cui X., Yao W., Yu X., Cen P., et al. Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer. Curr Mol Med 2013, 13:401-409.
109. Wong P.F., Abubakar S. LNCaP prostate cancer cells are insensitive to zinc-induced senescence. J Trace Elem Med Biol 2008, 22:242-247.
110. Rudolf E., Rudolf K., Cervinka M. Zinc induced apoptosis in HEP-2 cancer cells: the role of oxidative stress and mitochondria. Biofactors 2005, 23:107-120.
111. Yeh C.T., Yen G.C. Effect of sulforaphane on metallothionein expression and induction of apoptosis in human hepatoma HepG2 cells. Carcinogenesis 2005, 26:2138-2148.
112. Khan H.Y., Zubair H., Faisal M., Ullah M.F., Farhan M., Sarkar F.H., et al. Plant polyphenol induced cell death in human cancer cells involves mobilization of intracellular copper ions and reactive oxygen species generation: a mechanism for cancer chemopreventive action. Mol Nutr Food Res 2014, 58:437-446.
113. Bhat S.H., Azmi A.S., Hadi S.M. Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: involvement of endogenous copper and a putative mechanism for anticancer properties. Toxicol Appl Pharmacol 2007, 218:249-255.
114. Menendez J.A., Joven J., Aragonès G., Barrajón-Catalán E., Beltrán-Debón R., Borrás-Linares I., et al. Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil: a new family of gerosuppressant agents. Cell Cycle 2013, 12:555-578.
115. Jaskelioff M., Muller F.L., Paik J.H., Thomas E., Jiang S., Adams A.C., et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 2011, 469:102-106.
116. Bernardes De Jesus B., Schneeberger K., Vera E., Tejera A., Harley C.B., Blasco M.A. The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. Aging Cell 2011, 10:604-621.
117. Harley C.B., Liu W., Blasco M., Vera E., Andrews W.H., Briggs L.A., et al. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Res 2011, 14:45-56.
118. So M.W., Lee E.J., Lee H.S., Koo B.S., Kim Y.G., Lee C.K., et al. Protective effects of ginsenoside Rg3 on human osteoarthritic chondrocytes. Mod Rheumatol 2013, 23:104-111.
119. Shi A.W., Gu N., Liu X.M., Wang X., Peng Y.Z. Ginsenoside Rg1 enhances endothelial progenitor cell angiogenic potency and prevents senescence in vitro. J Int Med Res 2011, 39:1306-1318.
120. Liu J., Cai S.Z., Zhou Y., Zhang X.P., Liu D.F., Jiang R., et al. Senescence as a consequence of ginsenoside rg1 response on k562 human leukemia cell line. Asian Pac J Cancer Prev 2012, 13:6191-6196.
121. Sin S., Kim S.Y., Kim S.S. Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells. Int J Oncol 2012, 41:1669-1674.
122. Chen X., Zhang J., Fang Y., Zhao C., Zhu Y. Ginsenoside Rg1 delays tert-butyl hydroperoxide-induced premature senescence in human WI-38 diploid fibroblast cells. J Gerontol A Biol Sci Med Sci 2008, 63:253-264.
123. Yamashita S., Ogawa K., Ikei T., Udono M., Fujiki T., Katakura Y. SIRT1 prevents replicative senescence of normal human umbilical cord fibroblast through potentiating the transcription of human telomerase reverse transcriptase gene. Biochem Biophys Res Commun 2012, 417:630-634.
124. Li Y., Tollefsbol T.O. p16(INK4a) suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms. PLoS One 2011, 6:e17421.
125. Yuan Q., Peng J., Liu S.Y., Wang C.J., Xiang D.X., Xiong X.M., et al. Inhibitory effect of resveratrol derivative BTM-0512 on high glucose-induced cell senescence involves dimethylaminohydrolase/asymmetric dimethylarginine pathway. Clin Exp Pharmacol Physiol 2010, 37:630-635.
126. Schilder Y.D., Heiss E.H., Schachner D., Ziegler J., Reznicek G., Sorescu D., et al. NADPH oxidases 1 and 4 mediate cellular senescence induced by resveratrol in human endothelial cells. Free Radic Biol Med 2009, 46:1598-1606.
127. Hubbard B.P., Gomes A.P., Dai H., Li J., Case A.W., Considine T., et al. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 2013, 339:1216-1219.
128. Peltz L., Gomez J., Marquez M., Alencastro F., Atashpanjeh N., Quang T., et al. Resveratrol exerts dosage and duration dependent effect on human mesenchymal stem cell development. PLoS One 2012, 7:e37162.
129. Li Y.B., Zhong Z.F., Chen M.W., Bao J.L., Wu G.S., Zhang Q.W., et al. Bisdemethoxycurcumin increases Sirt1 to antagonize t-BHP-induced premature senescence in WI38 fibroblast cells. Evid Based Complement Alternat Med 2013, 2013:851714.
130. De Cecco M., Criscione S.W., Peterson A.L., Neretti N., Sedivy J.M., Kreiling J.A. Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues. Aging (Albany NY) 2013, 5:867-883.
131. Zempleni J., Chew Y.C., Bao B., Pestinger V., Wijeratne S.S. Repression of transposable elements by histone biotinylation. J Nutr 2009, 139:2389-2392.
132. Atamna H., Newberry J., Erlitzki R., Schultz C.S., Ames B.N. Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblasts. J Nutr 2007, 137:25-30.
133. Mathew R., Karantza-Wadsworth V., White E. Role of autophagy in cancer. Nat Rev Cancer 2007, 7:961-967.
134. Jones R.G., Plas D.R., Kubek S., Buzzai M., Mu J., Xu Y., et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 2005, 18:283-293.
135. Demidenko Z.N., Blagosklonny M.V. At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence. Cell Cycle 2009, 8:1901-1904.
136. Leontieva O.V., Paszkiewicz G., Demidenko Z.N., Blagosklonny M.V. Resveratrol potentiates rapamycin to prevent hyperinsulinemia and obesity in male mice on high fat diet. Cell Death Dis 2013, 4:e472.
137. Halicka H.D., Zhao H., Li J., Lee Y.S., Hsieh T.C., Wu J.M., et al. Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage-signaling. Aging (Albany NY) 2012, 4:952-965.
138. Wong T.F., Takeda T., Li B., Tsuiji K., Kondo A., Tadakawa M., et al. Curcumin targets the AKT-mTOR pathway for uterine leiomyosarcoma tumor growth suppression. Int J Clin Oncol 2013, [May 11. (in press)]. 10.1007/s10147-013-0563-4.
139. Kumar A., Prakash A., Dogra S. Protective effect of curcumin (Curcuma longa) against d-galactose-induced senescence in mice. J Asian Nat Prod Res 2011, 13:42-55.
140. Yagi H., Tan J., Tuan R.S. Polyphenols suppress hydrogen peroxide-induced oxidative stress in human bone-marrow derived mesenchymal stem cells. J Cell Biochem 2013, 114:1163-1173.
141. Sikora E., Bielak-Zmijewska A., Mosieniak G., Piwocka K. The promise of slow down ageing may come from curcumin. Curr Pharm Des 2010, 16:884-892.
142. Kashino G., Kodama S., Nakayama Y., Suzuki K., Fukase K., Goto M., et al. Relief of oxidative stress by ascorbic acid delays cellular senescence of normal human and Werner syndrome fibroblast cells. Free Radic Biol Med 2003, 35:438-443.
143. Esteban M.A., Wang T., Qin B., Yang J., Qin D., Cai J., et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 2010, 6:71-79.
144. Kim J.E., Jin D.H., Lee S.D., Hong S.W., Shin J.S., Lee S.K., et al. Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity. Int J Mol Med 2008, 22:651-655.
145. Furumoto K., Inoue E., Nagao N., Hiyama E., Miwa N. Age-dependent telomere shortening is slowed down by enrichment of intracellular vitamin C via suppression of oxidative stress. Life Sci 1998, 63:935-948.
146. Park J.H., Kim J.J., Bae Y.S. Involvement of PI3K-AKT-mTOR pathway in protein kinase CKII inhibition-mediated senescence in human colon cancer cells. Biochem Biophys Res Commun 2013, 433:420-425.
147. Han D.W., Lee M.H., Kim B., Lee J.J., Hyon S.H., Park J.C. Preventive effects of epigallocatechin-3-O-gallate against replicative senescence associated with p53 acetylation in human dermal fibroblasts. Oxid Med Cell Longev 2012, 2012:850684.
148. Lee J., Shin Y.K., Song J.Y., Lee K.W. Protective mechanism of morin against ultraviolet B-inducedcellular senescence in human keratinocyte stem cells. Int J Radiat Biol 2014, 90:20-28.
149. Martindale J.L., Holbrook N.J. Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 2002, 192:1-15.
150. Xu Y. Induction of genetic instability by gain-of-function p53 cancer mutants. Oncogene 2008, 27:3501-3507.
151. Matheu A., Maraver A., Klatt P., Flores I., Garcia-Cao I., Borras C., et al. Delayed ageing through damage protection by the Arf/p53 pathway. Nature 2007, 448:375-379.
152. Baran E.J. Metal complexes of carnosine. Biochemistry (Mosc) 2000, 65:789-797.
153. McFarland G.A., Holliday R. Further evidence for the rejuvenating effects of the dipeptide l-carnosine on cultured human diploid fibroblasts. Exp Gerontol 1999, 34:35-45.
154. Méplan C., Richard M.J., Hainaut P. Metalloregulation of the tumor suppressor protein p53: zinc mediates the renaturation of p53 after exposure to metal chelators in vitro and in intact cells. Oncogene 2000, 19:5227-5236.
155. Mocchegiani E., Costarelli L., Basso A., Giacconi R., Piacenza F., Malavolta M. Metallothioneins, ageing and cellular senescence: a future therapeutic target. Curr Pharm Des 2013, 19:1753-1764.
156. Sharif R., Thomas P., Zalewski P., Fenech M. The role of zinc in genomic stability. Mutat Res 2012, 733:111-121.
157. Hider R.C., Liu Z.D., Khodr H.H. Metal chelation of polyphenols. Methods Enzymol 2001, 335:190-203.
158. Belin S., Kaya F., Duisit G., Giacometti S., Ciccolini J., Fontés M. Antiproliferative effect of ascorbic acid is associated with the inhibition of genes necessary to cell cycle progression. PLoS One 2009, 4:e4409.
159. Felipe K.B., Benites J., Glorieux C., Sid B., Valenzuela M., Kviecinski M.R., et al. Antiproliferative effects of phenylaminonaphthoquinones are increased by ascorbate and associated with the appearance of a senescent phenotype in human bladder cancer cells. Biochem Biophys Res Commun 2013, 433:573-578.
160. Nesaretnam K., Yew W.W., Wahid M.B. Tocotrienols and cancer: beyond antioxidant activity. Eur J Lipid Sci Technol 2007, 109:445-452.
161. Sen C.K., Khanna S., Roy S., Packer L. Molecular basis of vitamin E action. Tocotrienol potently inhibits glutamate-induced pp 60(c-Src) kinase activation and death of HT4 neuronal cells. J Biol Chem 2000, 275:13049-13055.
162. Rein M.J., Renouf M., Cruz-Hernandez C., Actis-Goretta L., Thakkar S.K., Da Silva Pinto M. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy. Br J Clin Pharmacol 2013, 75:588-602.
163. Cherniack E.P. The potential influence of plant polyphenols on the aging process. Forsch Komplementmed 2010, 17:181-187.
164. Raederstorff D., Kunz I., Schwager J. Resveratrol, from experimental data to nutritional evidence: the emergence of a new food ingredient. Ann N Y Acad Sci 2013, 1290:136-141.
165. Carroll R.E., Benya R.V., Turgeon D.K., Vareed S., Neuman M., Rodriguez L., et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011, 4:354-364.
166. Magyar K., Halmosi R., Palfi A., Feher G., Czopf L., Fulop A., et al. Cardioprotection by resveratrol: a human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc 2012, 50:179-187.
167. Crandall J.P., Oram V., Trandafirescu G., Reid M., Kishore P., Hawkins M., et al. Pilot study of resveratrol in older adults with impaired glucose tolerance. J Gerontol A Biol Sci Med Sci 2012, 67:1307-1312.
168. Timmers S., Konings E., Bilet L., Houtkooper R.H., van de Weijer T., Goossens G.H., et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 2011, 14:612-622.
169. Yoshino J., Conte C., Fontana L., Mittendorfer B., Imai S., Schechtman K.B., et al. Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab 2012, 16:658-664.
170. Gliemann L., Schmidt J.F., Olesen J., Biensø R.S., Peronard S.L., Grandjean S.U., et al. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol 2013, 591:5047-5059.
171. Cheng A.L., Hsu C.H., Lin J.K., Hsu M.M., Ho Y.F., Shen T.S., et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001, 21:2895-2900.
172. Chuengsamarn S., Rattanamongkolgul S., Phonrat B., Tungtrongchitr R., Jirawatnotai S. Reduction of atherogenic risk in patients with type 2 diabetes by curcuminoid extract: a randomized controlled trial. J Nutr Biochem 2014, 25:144-150.
173. Akazawa N., Choi Y., Miyaki A., Tanabe Y., Sugawara J., Ajisaka R., et al. Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women. Nutr Res 2012, 32:795-799.
174. Sahebkar A. A systematic review and meta-analysis of randomized controlled trials investigating the effects of curcumin on blood lipid levels. Clin Nutr 2013, 10.1016/j.clnu.2013.09.012.
175. Schramm L. Going green: the role of the green tea component EGCG in chemoprevention. J Carcinog Mutagen 2013, 4:1000142.
176. Kanwar J., Taskeen M., Mohammad I., Huo C., Chan T.H., Dou Q.P. Recent advances on tea polyphenols. Front Biosci (Elite Ed) 2012, 4:111-131.
177. Khurana S., Venkataraman K., Hollingsworth A., Piche M., Tai T.C. Polyphenols: benefits to the cardiovascular system in health and in aging. Nutrients 2013, 5:3779-3827.
178. Mereles D., Hunstein W. Epigallocatechin-3-gallate (EGCG) for clinical trials: more pitfalls than promises?. Int J Mol Sci 2011, 12:5592-5603.
179. Williamson G., Manach C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr 2005, 81:243S-255S.
180. Hollman P.C., Katan M.B. Dietary flavonoids: intake, health effects and bioavailability. Food Chem Toxicol 1999, 37:937-942.
181. Oidtmann J., Schantz M., Mäder K., Baum M., Berg S., Betz M., et al. Preparation and comparative release characteristics of three anthocyanin encapsulation systems. J Agric Food Chem 2012, 60:844-851.
182. Schiborr C., Kocher A., Behnam D., Jandasek J., Toelstede S., Frank J. The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res 2014, [Epub ahead of print]. 10.1002/mnfr.201300724.
183. Nair H.B., Sung B., Yadav V.R., Kannappan R., Chaturvedi M.M., Aggarwal B.B. Delivery of antiinflammatory nutraceuticals by nanoparticles for the prevention and treatment of cancer. Biochem Pharmacol 2010, 80:1833-1843. [Dec 15].
184. Smoliga J.M., Colombo E.S., Campen M.J. A healthier approach to clinical trials evaluating resveratrol for primary prevention of age-related diseases in healthy populations. Aging (Albany NY) 2013, 5:495-506.
185. Ding Z., Wu C.J., Jaskelioff M., Ivanova E., Kost-Alimova M., Protopopov A., et al. Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases. Cell 2012, 148:896-907.
186. Iovine B., Iannella M.L., Nocella F., Pricolo M.R., Bevilacqua M.A. Carnosine inhibits KRAS-mediated HCT116 proliferation by affecting ATP and ROS production. Cancer Lett 2012, 315:122-128.
187. Gao Z., Xu M.S., Barnett T.L., Xu C.W. Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells. Biochem Biophys Res Commun 2011, 407:271-276.
188. Heiss E.H., Schilder Y.D., Dirsch V.M. Chronic treatment with resveratrol induces redox stress- and ataxia telangiectasia-mutated (ATM)-dependent senescence in p53-positive cancer cells. J Biol Chem 2007, 282:26759-26766.
189. Patel K.R., Andreadi C., Britton R.G., Horner-Glister E., Karmokar A., Sale S., et al. Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence. Sci Transl Med 2013, 5:205ra133.
190. Poulsen R.C., Watts A.C., Murphy R.J., Snelling S.J., Carr A.J., Hulley P.A. Glucocorticoids induce senescence in primary human tenocytes by inhibition of sirtuin 1 and activation of the p53/p21 pathway: in vivo and in vitro evidence. Ann Rheum Dis 2013, [Jun 1. (in press)].
191. Back J.H., Zhu Y., Calabro A., Queenan C., Kim A.S., Arbesman J., et al. Resveratrol-mediated downregulation of Rictor attenuates autophagic process and suppresses UV-induced skin carcinogenesis. Photochem Photobiol 2012, 88:1165-1172.
192. Liao P.C., Ng L.T., Lin L.T., Richardson C.D., Wang G.H., Lin C.C. Resveratrol arrests cell cycle and induces apoptosis in human hepatocellular carcinoma Huh-7 cells. J Med Food 2010, 13:1415-1423.
193. Luna C., Li G., Liton P.B., Qiu J., Epstein D.L., Challa P., et al. Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol 2009, 47:198-204.
194. Li Y.B., Gao J.L., Zhong Z.F., Hoi P.M., Lee S.M., Wang Y.T. Bisdemethoxycurcumin suppresses MCF-7 cells proliferation by inducing ROS accumulation and modulating senescence-related pathways. Pharmacol Rep 2013, 65:700-709.
195. Zamin L.L., Filippi-Chiela E.C., Dillenburg-Pilla P., Horn F., Salbego C., Lenz G. Resveratrol and quercetin cooperate to induce senescence-like growth arrest in C6 rat glioma cells. Cancer Sci 2009, 100:1655-1662.
196. Dasari A., Bartholomew J.N., Volonte D., Galbiati F. Oxidative stress induces premature senescence by stimulating caveolin-1 gene transcription through p38 mitogen-activated protein kinase/Sp1-mediated activation of two GC-rich promoter elements. Cancer Res 2006, 66:10805-10814.
197. Volonte D., Zhang K., Lisanti M.P., Galbiati F. Expression of caveolin-1 induces premature cellular senescence in primary cultures of murine fibroblasts. Mol Biol Cell 2002, 13:2502-2517.
198. Zhou B.R., Xu Y., Wu D., Permatasari F., Gao Y.Y., Luo D. Ginsenoside Rg1 protects human fibroblasts against psoralen- and UVA-induced premature senescence through a telomeric mechanism. Arch Dermatol Res 2012, 304:223-228.