Ayse Leyla Mindikoglu, M.D., M.P.H.; Weiwei Dang, PhD; Sung Yun Jung, PhD | Baylor College of Medicine
Competition Sponsor: US National Academy of Medicine
Awardee Year: 2023
DNA double-strand breaks and DNA methylation pattern changes (epigenetic change) are strongly associated with aging. Previous studies showed that fasting from dawn to dusk without eating or drinking (dawn-to-dusk dry fasting) showed upregulation of proteins associated with extreme longevity, increased autophagy, tumor suppression, DNA repair, and reduction in several oxidative stress and inflammatory biomarkers. Dawn-to-dusk dry fasting with meals just before and after fasting likely acts as a robust zeitgeber, aligns mealtimes with day-night cycles, and entrains metabolic regulators of the circadian clock to dawn and dusk, thereby increasing mRNA amplitude and improving downstream protein synthesis for multiple metabolic pathways. In this project, we will evaluate the changes in key regulator proteins and DNA methylation patterns in the peripheral blood mononuclear cells (PBMC) collected from healthy subjects and subjects with metabolic syndrome who fasted from dawn to dusk for 4 weeks. To quantify proteins in PBMC before, during, and after dawn-to-dusk fasting, we will perform nano ultra-high performance liquid chromatography-tandem mass spectrometry. We will perform DNA methylation array analysis using genomic DNA to estimate epigenetic age before, during, and after dawn-to-dusk fasting. This proof-of-concept study will be conducted by a unique team of experts in state-of-the-art facilities and provide a mechanistic understanding of the effects of dawn-to-dusk dry fasting on human DNA repair proteins and DNA methylation patterns. The results of this study will provide a valuable guide to the design of future larger-scale clinical studies on the health and longevity effects of the dawn-to-dusk dry fasting regimen.