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Nuclear Genomic Instability and Aging.

Niedernhofer LJ, Gurkar AU, Wang Y, Vijg J, Hoeijmakers JHJ, Robbins PD.

Annu Rev Biochem. 2018 Jun 20;87:295-322. doi: 10.1146/annurev-biochem-062917-012239.


Neurodegeneration as the presenting symptom in 2 adults with xeroderma pigmentosum complementation group F.

Shanbhag NM, Geschwind MD, DiGiovanna JJ, Groden C, Godfrey R, Yousefzadeh MJ, Wade EA, Niedernhofer LJ, Malicdan MCV, Kraemer KH, Gahl WA, Toro C.

Neurol Genet. 2018 Jun 8;4(3):e240. doi: 10.1212/NXG.0000000000000240. eCollection 2018 Jun.


Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation.

Zhao J, Zhang L, Mu X, Doebelin C, Nguyen W, Wallace C, Reay DP, McGowan SJ, Corbo L, Clemens PR, Wilson GM, Watkins SC, Solt LA, Cameron MD, Huard J, Niedernhofer LJ, Kamenecka TM, Robbins PD.

PLoS Biol. 2018 Jun 11;16(6):e2004663. doi: 10.1371/journal.pbio.2004663. eCollection 2018 Jun.


Hsp90 inhibitors as senolytic drugs to extend healthy aging.

Fuhrmann-Stroissnigg H, Niedernhofer LJ, Robbins PD.

Cell Cycle. 2018 Jun 9. doi: 10.1080/15384101.2018.1475828. [Epub ahead of print]


ERCC1-deficient cells and mice are hypersensitive to lipid peroxidation.

Czerwińska J, Nowak M, Wojtczak P, Dziuban-Lech D, Cieśla JM, Kołata D, Gajewska B, Barańczyk-Kuźma A, Robinson AR, Shane HL, Gregg SQ, Rigatti LH, Yousefzadeh MJ, Gurkar AU, McGowan SJ, Kosicki K, Bednarek M, Zarakowska E, Gackowski D, Oliński R, Speina E, Niedernhofer LJ, Tudek B.

Free Radic Biol Med. 2018 Jun 1;124:79-96. doi: 10.1016/j.freeradbiomed.2018.05.088. [Epub ahead of print]


Spontaneous DNA damage to the nuclear genome promotes senescence, redox imbalance and aging.

Robinson AR, Yousefzadeh MJ, Rozgaja TA, Wang J, Li X, Tilstra JS, Feldman CH, Gregg SQ, Johnson CH, Skoda EM, Frantz MC, Bell-Temin H, Pope-Varsalona H, Gurkar AU, Nasto LA, Robinson RAS, Fuhrmann-Stroissnigg H, Czerwinska J, McGowan SJ, Cantu-Medellin N, Harris JB, Maniar S, Ross MA, Trussoni CE, LaRusso NF, Cifuentes-Pagano E, Pagano PJ, Tudek B, Vo NV, Rigatti LH, Opresko PL, Stolz DB, Watkins SC, Burd CE, Croix CMS, Siuzdak G, Yates NA, Robbins PD, Wang Y, Wipf P, Kelley EE, Niedernhofer LJ.

Redox Biol. 2018 Jul;17:259-273. doi: 10.1016/j.redox.2018.04.007. Epub 2018 Apr 13.


Senotherapeutics for healthy ageing.

Niedernhofer LJ, Robbins PD.

Nat Rev Drug Discov. 2018 May;17(5):377. doi: 10.1038/nrd.2018.44. Epub 2018 Apr 13. No abstract available.


Oxidation Products of 5-Methyl Cytosine are Decreased in Senescent Cells and Tissues of Progeroid Mice.

Zarakowska E, Czerwinska J, Tupalska A, Yousefzadeh MJ, Gregg SQ, St Croix CM, Niedernhofer LJ, Foksinski M, Gackowski D, Szpila A, Starczak M, Tudek B, Olinski R.

J Gerontol A Biol Sci Med Sci. 2018 Feb 3. doi: 10.1093/gerona/gly012. [Epub ahead of print]


Circulating levels of monocyte chemoattractant protein-1 as a potential measure of biological age in mice and frailty in humans.

Yousefzadeh MJ, Schafer MJ, Noren Hooten N, Atkinson EJ, Evans MK, Baker DJ, Quarles EK, Robbins PD, Ladiges WC, LeBrasseur NK, Niedernhofer LJ.

Aging Cell. 2018 Apr;17(2). doi: 10.1111/acel.12706. Epub 2017 Dec 31.


ERCC4 variants identified in a cohort of patients with segmental progeroid syndromes.

Mori T, Yousefzadeh MJ, Faridounnia M, Chong JX, Hisama FM, Hudgins L, Mercado G, Wade EA, Barghouthy AS, Lee L, Martin GM, Nickerson DA, Bamshad MJ; University of Washington Center for Mendelian Genomics, Niedernhofer LJ, Oshima J.

Hum Mutat. 2018 Feb;39(2):255-265. doi: 10.1002/humu.23367. Epub 2017 Nov 17.


Identification of HSP90 inhibitors as a novel class of senolytics.

Fuhrmann-Stroissnigg H, Ling YY, Zhao J, McGowan SJ, Zhu Y, Brooks RW, Grassi D, Gregg SQ, Stripay JL, Dorronsoro A, Corbo L, Tang P, Bukata C, Ring N, Giacca M, Li X, Tchkonia T, Kirkland JL, Niedernhofer LJ, Robbins PD.

Nat Commun. 2017 Sep 4;8(1):422. doi: 10.1038/s41467-017-00314-z.


The Clinical Potential of Senolytic Drugs.

Kirkland JL, Tchkonia T, Zhu Y, Niedernhofer LJ, Robbins PD.

J Am Geriatr Soc. 2017 Oct;65(10):2297-2301. doi: 10.1111/jgs.14969. Epub 2017 Sep 4.


Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

Ngo K, Patil P, McGowan SJ, Niedernhofer LJ, Robbins PD, Kang J, Sowa G, Vo N.

Mech Ageing Dev. 2017 Sep;166:16-23. doi: 10.1016/j.mad.2017.08.007. Epub 2017 Aug 19.


Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice.

Proto JD, Lu A, Dorronsoro A, Scibetta A, Robbins PD, Niedernhofer LJ, Huard J.

PLoS One. 2017 Jun 22;12(6):e0179270. doi: 10.1371/journal.pone.0179270. eCollection 2017.


Advances in Therapeutic Approaches to Extend Healthspan: a perspective from the 2nd Scripps Symposium on the Biology of Aging.

Robbins PD, Niedernhofer LJ.

Aging Cell. 2017 Aug;16(4):610-614. doi: 10.1111/acel.12620. Epub 2017 Jun 6.


ADAMTS5 Deficiency Protects Mice From Chronic Tobacco Smoking-induced Intervertebral Disc Degeneration.

Ngo K, Pohl P, Wang D, Leme AS, Lee J, Di P, Roughley P, Robbins PD, Niedernhofer LJ, Sowa G, Kang JD, Shapiro SS, Vo NV.

Spine (Phila Pa 1976). 2017 Oct 15;42(20):1521-1528. doi: 10.1097/BRS.0000000000002258.


Systems biology guided by XCMS Online metabolomics.

Huan T, Forsberg EM, Rinehart D, Johnson CH, Ivanisevic J, Benton HP, Fang M, Aisporna A, Hilmers B, Poole FL, Thorgersen MP, Adams MWW, Krantz G, Fields MW, Robbins PD, Niedernhofer LJ, Ideker T, Majumder EL, Wall JD, Rattray NJW, Goodacre R, Lairson LL, Siuzdak G.

Nat Methods. 2017 Apr 27;14(5):461-462. doi: 10.1038/nmeth.4260. No abstract available.


New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463.

Zhu Y, Doornebal EJ, Pirtskhalava T, Giorgadze N, Wentworth M, Fuhrmann-Stroissnigg H, Niedernhofer LJ, Robbins PD, Tchkonia T, Kirkland JL.

Aging (Albany NY). 2017 Mar 8;9(3):955-963. doi: 10.18632/aging.101202.


Expansion of myeloid-derived suppressor cells with aging in the bone marrow of mice through a NF-κB-dependent mechanism.

Flores RR, Clauson CL, Cho J, Lee BC, McGowan SJ, Baker DJ, Niedernhofer LJ, Robbins PD.

Aging Cell. 2017 Jun;16(3):480-487. doi: 10.1111/acel.12571. Epub 2017 Feb 23.


Quantitative Analysis of Cellular Senescence in Culture and In Vivo.

Zhao J, Fuhrmann-Stroissnigg H, Gurkar AU, Flores RR, Dorronsoro A, Stolz DB, St Croix CM, Niedernhofer LJ, Robbins PD.

Curr Protoc Cytom. 2017 Jan 5;79:9.51.1-9.51.25. doi: 10.1002/cpcy.16.


Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage.

Yu Y, Cui Y, Niedernhofer LJ, Wang Y.

Chem Res Toxicol. 2016 Dec 19;29(12):2008-2039. Epub 2016 Nov 7. Review.


mTOR signaling plays a critical role in the defects observed in muscle-derived stem/progenitor cells isolated from a murine model of accelerated aging.

Takayama K, Kawakami Y, Lavasani M, Mu X, Cummins JH, Yurube T, Kuroda R, Kurosaka M, Fu FH, Robbins PD, Niedernhofer LJ, Huard J.

J Orthop Res. 2017 Jul;35(7):1375-1382. doi: 10.1002/jor.23409. Epub 2016 Sep 22.


Molecular pathology endpoints useful for aging studies.

Niedernhofer LJ, Kirkland JL, Ladiges W.

Ageing Res Rev. 2017 May;35:241-249. doi: 10.1016/j.arr.2016.09.012. Epub 2016 Oct 6. Review.


Smartphone Analytics: Mobilizing the Lab into the Cloud for Omic-Scale Analyses.

Montenegro-Burke JR, Phommavongsay T, Aisporna AE, Huan T, Rinehart D, Forsberg E, Poole FL, Thorgersen MP, Adams MW, Krantz G, Fields MW, Northen TR, Robbins PD, Niedernhofer LJ, Lairson L, Benton HP, Siuzdak G.

Anal Chem. 2016 Oct 4;88(19):9753-9758. Epub 2016 Sep 15.


Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms.

Burd CE, Gill MS, Niedernhofer LJ, Robbins PD, Austad SN, Barzilai N, Kirkland JL.

J Gerontol A Biol Sci Med Sci. 2016 Nov;71(11):1388-1394. Epub 2016 Aug 16.


Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors.

Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, Dai HM, Ling YY, Stout MB, Pirtskhalava T, Giorgadze N, Johnson KO, Giles CB, Wren JD, Niedernhofer LJ, Robbins PD, Kirkland JL.

Aging Cell. 2016 Jun;15(3):428-35. doi: 10.1111/acel.12445. Epub 2016 Mar 18.


In vivo detection and replication studies of α-anomeric lesions of 2'-deoxyribonucleosides.

Amato NJ, Zhai Q, Navarro DC, Niedernhofer LJ, Wang Y.

Nucleic Acids Res. 2015 Sep 30;43(17):8314-24. doi: 10.1093/nar/gkv725. Epub 2015 Jul 21.


Simultaneous Quantification of Methylated Cytidine and Adenosine in Cellular and Tissue RNA by Nano-Flow Liquid Chromatography-Tandem Mass Spectrometry Coupled with the Stable Isotope-Dilution Method.

Fu L, Amato NJ, Wang P, McGowan SJ, Niedernhofer LJ, Wang Y.

Anal Chem. 2015 Aug 4;87(15):7653-9. doi: 10.1021/acs.analchem.5b00951. Epub 2015 Jul 21.


The Achilles' heel of senescent cells: from transcriptome to senolytic drugs.

Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Hubbard GB, Lenburg M, O'Hara SP, LaRusso NF, Miller JD, Roos CM, Verzosa GC, LeBrasseur NK, Wren JD, Farr JN, Khosla S, Stout MB, McGowan SJ, Fuhrmann-Stroissnigg H, Gurkar AU, Zhao J, Colangelo D, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Niedernhofer LJ, Kirkland JL.

Aging Cell. 2015 Aug;14(4):644-58. doi: 10.1111/acel.12344. Epub 2015 Apr 22.


NF-κB activation with aging: characterization and therapeutic inhibition.

Zhao J, Li X, McGowan S, Niedernhofer LJ, Robbins PD.

Methods Mol Biol. 2015;1280:543-57. doi: 10.1007/978-1-4939-2422-6_32.


Comparison of mice with accelerated aging caused by distinct mechanisms.

Gurkar AU, Niedernhofer LJ.

Exp Gerontol. 2015 Aug;68:43-50. doi: 10.1016/j.exger.2015.01.045. Epub 2015 Jan 21. Review.


Tet-mediated formation of 5-hydroxymethylcytosine in RNA.

Fu L, Guerrero CR, Zhong N, Amato NJ, Liu Y, Liu S, Cai Q, Ji D, Jin SG, Niedernhofer LJ, Pfeifer GP, Xu GL, Wang Y.

J Am Chem Soc. 2014 Aug 20;136(33):11582-5. doi: 10.1021/ja505305z. Epub 2014 Aug 7.


Choline phosphate cytidylyltransferase-α is a novel antigen detected by the anti-ERCC1 antibody 8F1 with biomarker value in patients with lung and head and neck squamous cell carcinomas.

Vaezi AE, Bepler G, Bhagwat NR, Malysa A, Rubatt JM, Chen W, Hood BL, Conrads TP, Wang L, Kemp CE, Niedernhofer LJ.

Cancer. 2014 Jun 15;120(12):1898-907. doi: 10.1002/cncr.28643. Epub 2014 Apr 1.


Pharmacologic IKK/NF-κB inhibition causes antigen presenting cells to undergo TNFα dependent ROS-mediated programmed cell death.

Tilstra JS, Gaddy DF, Zhao J, Davé SH, Niedernhofer LJ, Plevy SE, Robbins PD.

Sci Rep. 2014 Jan 10;4:3631. doi: 10.1038/srep03631.


Investigating the role of DNA damage in tobacco smoking-induced spine degeneration.

Nasto LA, Ngo K, Leme AS, Robinson AR, Dong Q, Roughley P, Usas A, Sowa GA, Pola E, Kang J, Niedernhofer LJ, Shapiro S, Vo NV.

Spine J. 2014 Mar 1;14(3):416-23. doi: 10.1016/j.spinee.2013.08.034. Epub 2013 Nov 6.


DNA damage triggers a chronic autoinflammatory response, leading to fat depletion in NER progeria.

Karakasilioti I, Kamileri I, Chatzinikolaou G, Kosteas T, Vergadi E, Robinson AR, Tsamardinos I, Rozgaja TA, Siakouli S, Tsatsanis C, Niedernhofer LJ, Garinis GA.

Cell Metab. 2013 Sep 3;18(3):403-15. doi: 10.1016/j.cmet.2013.08.011.


Age-related dystrophic changes in corneal endothelium from DNA repair-deficient mice.

Roh DS, Du Y, Gabriele ML, Robinson AR, Niedernhofer LJ, Funderburgh JL.

Aging Cell. 2013 Dec;12(6):1122-31. doi: 10.1111/acel.12143. Epub 2013 Sep 1.


Identification of microRNAs dysregulated in cellular senescence driven by endogenous genotoxic stress.

Nidadavolu LS, Niedernhofer LJ, Khan SA.

Aging (Albany NY). 2013 Jun;5(6):460-73.


An overview of underlying causes and animal models for the study of age-related degenerative disorders of the spine and synovial joints.

Vo N, Niedernhofer LJ, Nasto LA, Jacobs L, Robbins PD, Kang J, Evans CH.

J Orthop Res. 2013 Jun;31(6):831-7. doi: 10.1002/jor.22204. Epub 2013 Mar 11. Review.


Isolation of muscle-derived stem/progenitor cells based on adhesion characteristics to collagen-coated surfaces.

Lavasani M, Lu A, Thompson SD, Robbins PD, Huard J, Niedernhofer LJ.

Methods Mol Biol. 2013;976:53-65. doi: 10.1007/978-1-62703-317-6_5.


Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration.

Nasto LA, Robinson AR, Ngo K, Clauson CL, Dong Q, St Croix C, Sowa G, Pola E, Robbins PD, Kang J, Niedernhofer LJ, Wipf P, Vo NV.

J Orthop Res. 2013 Jul;31(7):1150-7. doi: 10.1002/jor.22320. Epub 2013 Feb 6.


DNA damage drives accelerated bone aging via an NF-κB-dependent mechanism.

Chen Q, Liu K, Robinson AR, Clauson CL, Blair HC, Robbins PD, Niedernhofer LJ, Ouyang H.

J Bone Miner Res. 2013 May;28(5):1214-28. doi: 10.1002/jbmr.1851.


Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs.

Nasto LA, Wang D, Robinson AR, Clauson CL, Ngo K, Dong Q, Roughley P, Epperly M, Huq SM, Pola E, Sowa G, Robbins PD, Kang J, Niedernhofer LJ, Vo NV.

Mech Ageing Dev. 2013 Jan-Feb;134(1-2):35-42. doi: 10.1016/j.mad.2012.11.002. Epub 2012 Dec 19.


Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington's disease.

Xun Z, Rivera-Sánchez S, Ayala-Peña S, Lim J, Budworth H, Skoda EM, Robbins PD, Niedernhofer LJ, Wipf P, McMurray CT.

Cell Rep. 2012 Nov 29;2(5):1137-42. doi: 10.1016/j.celrep.2012.10.001. Epub 2012 Nov 1.


Cell autonomous and nonautonomous mechanisms drive hematopoietic stem/progenitor cell loss in the absence of DNA repair.

Cho JS, Kook SH, Robinson AR, Niedernhofer LJ, Lee BC.

Stem Cells. 2013 Mar;31(3):511-25. doi: 10.1002/stem.1261.


A quantitative assay for assessing the effects of DNA lesions on transcription.

You C, Dai X, Yuan B, Wang J, Wang J, Brooks PJ, Niedernhofer LJ, Wang Y.

Nat Chem Biol. 2012 Oct;8(10):817-22.


NF-κB inhibition delays DNA damage-induced senescence and aging in mice.

Tilstra JS, Robinson AR, Wang J, Gregg SQ, Clauson CL, Reay DP, Nasto LA, St Croix CM, Usas A, Vo N, Huard J, Clemens PR, Stolz DB, Guttridge DC, Watkins SC, Garinis GA, Wang Y, Niedernhofer LJ, Robbins PD.

J Clin Invest. 2012 Jul;122(7):2601-12. doi: 10.1172/JCI45785. Epub 2012 Jun 18.


Comparison of ERCC1/XPF genetic variation, mRNA and protein levels in women with advanced stage ovarian cancer treated with intraperitoneal platinum.

Deloia JA, Bhagwat NR, Darcy KM, Strange M, Tian C, Nuttall K, Krivak TC, Niedernhofer LJ.

Gynecol Oncol. 2012 Sep;126(3):448-54. doi: 10.1016/j.ygyno.2012.05.006. Epub 2012 May 16.


Endogenous formation and repair of oxidatively induced G[8-5 m]T intrastrand cross-link lesion.

Wang J, Cao H, You C, Yuan B, Bahde R, Gupta S, Nishigori C, Niedernhofer LJ, Brooks PJ, Wang Y.

Nucleic Acids Res. 2012 Aug;40(15):7368-74. Epub 2012 May 11.


Multiple DNA binding domains mediate the function of the ERCC1-XPF protein in nucleotide excision repair.

Su Y, Orelli B, Madireddy A, Niedernhofer LJ, Schärer OD.

J Biol Chem. 2012 Jun 22;287(26):21846-55. doi: 10.1074/jbc.M111.337899. Epub 2012 Apr 30.

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