I had AI do a quick summary of a very comprehensive deep dive study of Horvath’s 48 aging related genes from the first preprint of his seminal paper Universal DNA methylation age across mammalian tissues -Nature Aging August 2023- The deep dive will be available in my upcoming book on the subject
here’s what it gave us:
What follows is an overview of Stephen Horvath’s Universal Mammalian Epigenetic Aging system. This updated review:
Clarifies that Thymine DNA Glycosylase (TDG), not TET enzymes, is the primary mechanism preventing hypermethylation of these aging-related genes (TDG is α-ketoglutarate dependent).
Explains that the initial 48 genes come from Horvath’s first preprint, and subsequent revisions have added or changed several genes (including transcription factor SP1).
Highlights how SP1 ties together MAO-A/MAO-B, FAD sequestration, WRN protein expression, and a potential impact on aging processes.
Presents a CD38/NAD+ analysis of the 48 genes, discussing how some of them may influence CD38 activity, thereby modulating NAD+ levels.
Throughout, we underscore the interplay of GABA–α-KG–glutamate, the overrepresentation of splicing-related genes, and the newly emphasized roles of SP1 and MAO in driving epigenetic and metabolic shifts that contribute to aging.