Steve Horvath, Ph.D.

Professor of Human Genetics & Bio-statistics UCLA

Dr. Horvath is an aging researcher and bioinformatician whose research ranges from epidemiology, chronic diseases, epigenetics, to systems biology. He developed systemic biologic approaches such as weighted gene co-expression network analysis. He works on all aspects of biomarker development with a particular focus on genomic biomarkers of aging. He developed a highly accurate multi-tissue biomarker of aging known as the epigenetic clock. Salient features of the epigenetic clock include its high accuracy and its applicability to a broad spectrum of tissues and cell types. He develops and applies methods for analyzing and integrating gene expression-, DNA methylation-, microRNA, genetic marker-, and complex phenotype data. His lab members apply and develop data mining methods to study a broad spectrum of diseases, e.g. aging research, cancer, cardiovascular disease, HIV, Huntington's disease, neurodegenerative diseases.

FOCUS AREAS

• Epigenetic Clock Theory of Aging. Horvath's development of the DNA methylation based age estimation method known as epigenetic clock was featured in Nature magazine. In 2011, Horvath co-authored the first article that described an age estimation method based on DNA methylation levels from saliva. In 2013, Horvath published a single author article on a multi-tissue age estimation method that applies to all nucleated cells, tissues, and organs. This discovery, known as the Horvath clock, was unexpected because cell types differ in terms of the their DNA methylation patterns and age related DNA methylation changes tend to be tissue specific. Horvath demonstrated that DNA methylation age has the following properties: it is close to zero for embryonic and induced pluripotent stem cells, it correlates with cell passage number, it gives rise to a highly heritable measure of age acceleration; and is applicable to chimpanzees. Since the Horvath clock allows one to contrast the ages of different tissues from the same individuals, it can be used to identify tissues that show evidence of increased or decreased age.

aging critical publications

• Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018 Jun;19(6):371-384. doi: 10.1038/s41576-018-0004-3. Review. PMID: 29643443

• Lu AT, Xue L, Salfati EL, Chen BH, Ferrucci L, Levy D, Joehanes R, Murabito JM, Kiel DP, Tsai PC, Yet I, Bell JT, Mangino M, Tanaka T, McRae AF, Marioni RE, Visscher PM, Wray NR, Deary IJ, Levine ME, Quach A, Assimes T, Tsao PS, Absher D, Stewart JD, Li Y, Reiner AP, Hou L, Baccarelli AA, Whitsel EA, Aviv A, Cardona A, Day FR, Wareham NJ, Perry JRB, Ong KK, Raj K, Lunetta KL, Horvath S (2018) GWAS of epigenetic aging rates in blood reveals a critical role for TERT. Nat Commun. 2018 Jan 26;9(1):387. doi: 10.1038/s41467-017-02697-5. PMID: 29374233

• Chen BH, Marioni RE, Colicino E, Peters MJ, Ward-Caviness CK, Tsai PC, Roetker NS, Just AC, Demerath EW, Guan W, Bressler J, Fornage M, Studenski S, Vandiver AR, Moore AZ, Tanaka T, Kiel DP, Liang L, Vokonas P, Schwartz J, Lunetta KL, Murabito JM, Bandinelli S, Hernandez DG, Melzer D, Nalls M, Pilling LC, Price TR, Singleton AB, et al, Absher D, Assimes T, Levine ME, Lu AT, Tsao PS, Hou L, Manson JE, Carty CL, LaCroix AZ, Reiner AP, Spector TD, Feinberg AP, Levy D, Baccarelli A, van Meurs J, Bell JT, Peters A, Deary IJ, Pankow JS, Ferrucci L, Horvath S (2016) DNA methylation-based measures of biological age: meta-analysis predicting time to death. Aging (Albany NY). 2016 Sep 28;8(9):1844-1865. doi: 10.18632/aging.101020. PMID: 27690265 PMCID: PMC5076441

• Horvath S, Garagnani P, Bacalini MG, Pirazzini C, Salvioli S, Gentilini D, DiBlasio AM, Giuliani C, Tung S, Vinters HV, Franceschi C (2015) Accelerated Epigenetic Aging in Down Syndrome. Aging Cell. 9 FEB 2015 DOI: 10.1111/acel.12325 PMID: 25678027 

• 5Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol. 2013 Oct 
  21;14(10):R115. PMCID: PMC4015143