Introduction

Six in ten adults in the United States have at least one chronic disease and four in ten adults have two or more [1]. These diseases are a major cause of morbidity and mortality and they put a significant burden on the healthcare system as well as the society at large [2]. Aging itself has been identified as a common driver of chronic diseases and an important target for extending human healthspan [3]. It has also been estimated that if we improve our collective healthspan by just one year the calculated savings are worth $38 trillion dollars, and if by 10 years those savings jump to $367 trillion dollars [4]. Biological age clocks, based on DNA methylation marks, have become important surrogate markers to assess the effectiveness of interventions at reducing biological age, with the expectation that biological age reductions will compress morbidity and extend mortality [5, 6].

Modifiable lifestyle factors, including concentrated exposure to dietary “epinutrients”, have been suggested to be able to favorably influence DNA methylation-based clocks and therefore have the potential to compress morbidity and extend mortality [7]. Epinutrients may be defined as dietary nutrients that provide either substrates or cofactors for DNA methylation activity or influence the expression or rate of activity of DNA methylation-related enzymes. Folate and betaine, for example, are cofactors in methylation biosynthetic pathways, alpha ketoglutarate, vitamin C, and vitamin A are ten-eleven translocation (TET) demethylase cofactors and modulators, and curcumin, epigallocatechin gallate (EGCG), rosmarinic acid, quercetin, and luteolin are known polyphenolic modulators of DNA methyl transferase (DMNT) enzymes [8, 9].

The modifiable lifestyle intervention used by participants in this case series was first investigated in a pilot clinical trial in which participants (all men between the ages of 50-72 years) reduced their biological age by an average of 3.23 years as compared to controls [7]. The case series reported on herein was conducted to further the investigation of a modifiable lifestyle intervention that was largely the same in other populations; importantly in women.