Steve Horvath
{{short description|German–American aging researcher, geneticist and biostatistician}}
{{Infobox academic
| name = Steve Horvath
| image = Steve Horvath, UCLA professor, presenting a talk June 2015.jpg
| alt =
| caption = Horvath presenting a talk in 2015
| birth_date =
| birth_place = Frankfurt, Germany
| nationality =
| other_names =
| citizenship =
| education =
| alma_mater = Technische Universität Berlin
(BS)
University of North Carolina, Chapel Hill
(PhD)
Harvard School of Public Health
(Sc.D)
| doctoral_advisor = Robert Brown Gardner
Nan Laird
| occupation = Professor of Human Genetics & Biostatistics
| years_active =
| workplaces = UCLA
Altos Labs
| known_for = Developing the epigenetic clock (Horvath clock) and weighted correlation network analysis
}}
Steve Horvath is a German–American aging researcher, geneticist, and biostatistician. He is a professor at the University of California, Los Angeles. He is known for developing the Horvath aging clock, which is a highly accurate molecular biomarker of aging, and for developing weighted correlation network analysis. His work on the genomic biomarkers of aging, the aging process, and many age related diseases/conditions has earned him several research awards. Horvath is a principal investigator at the anti-aging startup Altos Labs{{Cite web|url=https://www.technologyreview.com/2021/09/04/1034364/altos-labs-silicon-valleys-jeff-bezos-milner-bet-living-forever/|title = Meet Altos Labs, Silicon Valley's latest wild bet on living forever| date=4 September 2021 }} and co-founder of nonprofit Clock Foundation.{{Cite web|url=https://clockfoundation.org/about-the-clock-foundation/| date=12 October 2023 | title=About the Clock Foundation }}
Background
Horvath was born 1967 in Frankfurt, Germany; as the family name Horvath indicates, he is of Hungarian ancestry. He received his Diplom in Mathematics and Physics at Technische Universität Berlin, graduating in 1989.{{cite web|url=https://ph.ucla.edu/faculty/horvath|title=About the universities|access-date=20 August 2020|publisher=University of California Los Angeles}} He received his Ph.D. in mathematics at the UNC Chapel Hill in 1995 and his Sc.D. in biostatistics at Harvard in 2000. In 2000, Horvath joined the faculty of the University of California, Los Angeles, where he is a professor of human genetics at the David Geffen School of Medicine at UCLA and of biostatistics at the UCLA Fielding School of Public Health.
Work on the epigenetic clock
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 their DNA methylation patterns and age related DNA methylation changes tend to be tissue specific. In his article, he demonstrated that estimated age, also referred to as 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 it 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.
=Genetics of aging=
Horvath published the first article demonstrating that trisomy 21 (Down syndrome) is associated with strong epigenetic age acceleration effects in both blood and brain tissue.
Using genome-wide association studies, Horvath's team identified the first genetic markers (SNPs) that exhibit genome-wide significant associations with epigenetic aging rates – in particular, the first genome-wide significant genetic loci associated with epigenetic aging rates in blood notably the telomerase reverse transcriptase gene (TERT) locus.{{cite journal |last1=Lu |first1=Ake T. |last2=Xue |first2=Luting |last3=Salfati |first3=Elias L. |last4=Chen |first4=Brian H. |last5=Ferrucci |first5=Luigi |last6=Levy |first6=Daniel |last7=Joehanes |first7=Roby |last8=Murabito |first8=Joanne M. |last9=Kiel |first9=Douglas P. |last10=Tsai |first10=Pei-Chien |last11=Yet |first11=Idil |last12=Bell |first12=Jordana T. |last13=Mangino |first13=Massimo |last14=Tanaka |first14=Toshiko |last15=McRae |first15=Allan F. |last16=Marioni |first16=Riccardo E. |last17=Visscher |first17=Peter M. |last18=Wray |first18=Naomi R. |last19=Deary |first19=Ian J. |last20=Levine |first20=Morgan E. |last21=Quach |first21=Austin |last22=Assimes |first22=Themistocles |last23=Tsao |first23=Philip S. |last24=Absher |first24=Devin |last25=Stewart |first25=James D. |last26=Li |first26=Yun |last27=Reiner |first27=Alex P. |last28=Hou |first28=Lifang |last29=Baccarelli |first29=Andrea A. |last30=Whitsel |first30=Eric A. |last31=Aviv |first31=Abraham |last32=Cardona |first32=Alexia |last33=Day |first33=Felix R. |last34=Wareham |first34=Nicholas J. |last35=Perry |first35=John R. B. |last36=Ong |first36=Ken K. |last37=Raj |first37=Kenneth |last38=Lunetta |first38=Kathryn L. |last39=Horvath |first39=Steve |title=GWAS of epigenetic aging rates in blood reveals a critical role for TERT |journal=Nature Communications |date=26 January 2018 |volume=9 |issue=1 |pages=387 |doi=10.1038/s41467-017-02697-5 |pmid=29374233 |pmc=5786029 |bibcode=2018NatCo...9..387L }}
As part of this work, his team uncovered a paradoxical relationship: genetic variants associated with longer leukocyte telomere length in the TERT gene paradoxically confer higher epigenetic age acceleration in blood.
=Work in biodemography=
Horvath proposed that slower epigenetic aging rates could explain the mortality advantage of women and the Hispanic mortality paradox.{{cite journal |last1=Horvath |first1=Steve |last2=Gurven |first2=Michael |last3=Levine |first3=Morgan E. |last4=Trumble |first4=Benjamin C. |last5=Kaplan |first5=Hillard |last6=Allayee |first6=Hooman |last7=Ritz |first7=Beate R. |last8=Chen |first8=Brian |last9=Lu |first9=Ake T. |last10=Rickabaugh |first10=Tammy M. |last11=Jamieson |first11=Beth D. |last12=Sun |first12=Dianjianyi |last13=Li |first13=Shengxu |last14=Chen |first14=Wei |last15=Quintana-Murci |first15=Lluis |last16=Fagny |first16=Maud |last17=Kobor |first17=Michael S. |last18=Tsao |first18=Philip S. |last19=Reiner |first19=Alexander P. |last20=Edlefsen |first20=Kerstin L. |last21=Absher |first21=Devin |last22=Assimes |first22=Themistocles L. |title=An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease |journal=Genome Biology |date=11 August 2016 |volume=17 |issue=1 |pages=171 |doi=10.1186/s13059-016-1030-0 |pmid=27511193 |pmc=4980791 |doi-access=free }}
=Lifestyle factors and nutrition=
Horvath published the first large scale study of the effect of lifestyle factors on epigenetic aging rates.{{cite journal |last1=Quach |first1=Austin |last2=Levine |first2=Morgan E. |last3=Tanaka |first3=Toshiko |last4=Lu |first4=Ake T. |last5=Chen |first5=Brian H. |last6=Ferrucci |first6=Luigi |last7=Ritz |first7=Beate |last8=Bandinelli |first8=Stefania |last9=Neuhouser |first9=Marian L. |last10=Beasley |first10=Jeannette M. |last11=Snetselaar |first11=Linda |last12=Wallace |first12=Robert B. |last13=Tsao |first13=Philip S. |last14=Absher |first14=Devin |last15=Assimes |first15=Themistocles L. |last16=Stewart |first16=James D. |last17=Li |first17=Yun |last18=Hou |first18=Lifang |last19=Baccarelli |first19=Andrea A. |last20=Whitsel |first20=Eric A. |last21=Horvath |first21=Steve |title=Epigenetic clock analysis of diet, exercise, education, and lifestyle factors |journal=Aging |date=14 February 2017 |volume=9 |issue=2 |pages=419–446 |doi=10.18632/aging.101168 |pmid=28198702 |pmc=5361673 }}
These cross sectional of epigenetic aging rates in blood confirm the conventional wisdom regarding the benefits of education, eating a high plant diet with lean meats, moderate alcohol consumption, physical activity and the risks associated with metabolic syndrome.
=Epigenetic clock theory of aging=
Horvath and Raj proposed an epigenetic clock theory of aging{{cite journal |last1=Horvath |first1=Steve |last2=Raj |first2=Kenneth |title=DNA methylation-based biomarkers and the epigenetic clock theory of ageing |journal=Nature Reviews Genetics |date=11 April 2018 |volume=19 |issue=6 |pages=371–384 |doi=10.1038/s41576-018-0004-3 |pmid=29643443 |s2cid=4709691 }} which views biological aging as an unintended consequence of both developmental programs and maintenance program, the molecular footprints of which give rise to DNA methylation age estimators. DNAm age is viewed as a proximal readout of a collection of innate ageing processes that conspire with other, independent root causes of aging, to the detriment of tissue function.
Weighted correlation network analysis
Horvath and members of his lab developed a widely used systems biological data mining technique known as weighted correlation network analysis. He published a book on weighted network analysis and genomic applications.
Awards and honors
Horvath has won several awards for his work on the epigenetic clock.
- 2017 Allen Distinguished Investigator award for clock studies in vertebrates
- 2019 Open Philanthropy Project award for mechanistic studies of the epigenetic clock
- 2019 Schober Award for outstanding and innovative research in the field of ageing
- 2022 Nathan W. Shock Award
- 2022 Fellow of the American Statistical Association{{cite web|url=https://www.amstat.org/docs/default-source/amstat-documents/pdfs/fellows/fellows2022.pdf|title=ASA 2022 Fellows|publisher=American Statistical Association|access-date=2022-07-20}}
- 2023 WNAR Outstanding Impact Award for Epigenetic Clocks and Weighted Correlation Network Analysis{{cite web|url=
https://wnar.org/news/13226588|title= IBS/WNAR Outstanding Impact Award and Lectureship| publisher=International Biometric Society}}
References
{{reflist|30em|refs=
{{cite news |author= |title= Open Philanthropy award for epigenetic clock research by Steve Horvath
|url= https://www.openphilanthropy.org/focus/scientific-research/ucla-epigenetic-clock-research
|location=openphilanthropy.org |date=April 2019 }}
| url =http://www.aging-us.com/article/no9ssRw2iNbWETXwP/text | journal = Aging| volume =8 | issue = 7| pages =1485–512 | pmid= 27479945 | pmc= 4993344| doi=10.18632/aging.101005}}
}}
{{Authority control}}
{{DEFAULTSORT:Horvath, Steve}}
Category:American people of Hungarian descent
Category:German people of Hungarian descent
Category:Educators from California
Category:David Geffen School of Medicine at UCLA faculty
Category:Harvard T.H. Chan School of Public Health alumni
Category:Technische Universität Berlin alumni
Category:University of North Carolina alumni