Labroots’ virtual events are designed to spark impactful scientific discussions while connecting with individuals worldwide who are either in your field of study or have similar scientific interests. These virtual events proudly host a poster discussion hour where attendees can discuss their pre-submitted posters with a worldwide audience and answer questions about their research. This year’s Drug Discovery & Development Virtual Event (now available On Demand) highlighted an exceptional study involving premature aging disorders and heterochromatin content. This astounding study comes from Dr. Jong-Hyuk Lee, who is an Assistant Professor in the Department of Biomedical Sciences at the Mercer University School of Medicine.
Dr. Lee’s poster investigated a connection between heterochromatin content and DNA damage vulnerability in two known aging disorders, Xeroderma Pigmentosum (XPA) and Ataxia-Telangiectasia (ATM), with XPA preventing DNA repair from ultraviolet (UV) radiation and ATM resulting in a wider range of DNA damage, including impaired coordination and blood vessel deformities in the eyes and skin. Heterochromatin protects DNA against damaging agents, and naturally lost as we age. Its breakdown has also been found to contribute to a variety of aging disorders.
For the study, the researchers subjected XPA and ATM cells to check if they also have heterochromatin loss, with the goal of identifying how this influences sensitivity against oxidative DNA damage within the XPA and ATM cells. While they hypothesized a reduction in heterochromatin content, the team discovered the opposite occurred as increased heterochromatin in these cells.
Further results showed the acute oxidative stress-induced XPA and ATM cells exhibited decreased levels of chromatin poly(ADP-ribosyl)ation (PARylation), which is involved in DNA repair, indicating the stress-induced XPA and ATM cells experienced decreased levels of DNA damage. Interestingly, they also identified XPA and ATM cells having increased levels of PARylation in non-stressed conditions. In the future, the team aspires to dive deeper into the processes responsible for this behavior.
Regarding how he thinks this project contributes to the larger ongoing themes in the field of drug discovery & development, Dr. Lee tells Labroots, “In the field of molecular gerontology, nicotinamide adenine dinucleotide (NAD⁺) supplementation has garnered significant attention from researchers. NAD⁺ is a crucial coenzyme involved in key cellular processes, including energy metabolism, mitochondrial function, and DNA repair. Especially, it is a building block for chromatin PARylation under DNA damage. Studies have shown that intracellular NAD⁺ levels decline significantly with age, perhaps by accumulated DNA damage, contributing to mitochondrial dysfunction, metabolic decline, and impaired cellular repair mechanisms."
Dr. Lee continues, "Moreover, increased DNA damage and epigenetic histone modifications are closely linked to NAD⁺ availability. Sirtuins (SIRT1-7), a family of NAD⁺-dependent deacetylases, play a pivotal role in regulating chromatin structure, gene expression, and DNA damage responses. Thus, exploring the mechanisms and consequences of NAD⁺-regulated histone modifications could provide deeper insights into the molecular basis of aging and potential therapeutic strategies for age-related diseases.”
Dr. Lee is actively seeing a graduate student to join his lab, located at the picturesque Mercer University School of Medicine Savannah Campus. To follow Dr. Lee’s research and career and to connect with him, please check out his Mercer University profile and LinkedIn page.
