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.
Horvath published the first article demonstrating that trisomy 21 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 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 locus. 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.
Lifestyle factors and nutrition
Horvath published the first large scale study of the effect of lifestyle factors on epigenetic aging rates. 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.
Horvath and Raj proposed an epigenetic clock theory of aging 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
