Tuberculosis Causes Premature Cellular Aging

An epigenetic study conducted by researchers at Baylor College of Medicine in Texas has found that the cells of humans and animals who have recovered from tuberculosis are prematurely aged up to 12 to 14 years. The findings potentially explain why survivors of tuberculosis have a higher risk of recurrent infection and death, and support epigenetic analysis as standard of care for the disease.  

Epigenetics studies how DNA is coiled, which changes as we age. Across multiple cohorts and tissue types, the researchers found that tuberculosis induced perturbations in epigenetic regulation, specifically in the regulation mediated by DNA methylation. These changes correlated with oxidative stress-induced senescence and were associated with premature cellular aging. These results were seen across both humans and guinea pigs—a standardized animal model for tuberculosis. The severity of the infection also could play a role in the aging of the cells.

Dr. Andrew DiNardo, assistant professor of infectious diseases at Baylor College of Medicine and senior author of the paper, says that premature aging is an important area to look into after any severe infection, including sepsis or even SARS-CoV-2.

“A multi-omic epigenetic clock assay could become part of the standard of care for infectious diseases and further inform increased risk for comorbidities after chronic conditions or environmental exposure,” adds Dr. Cristian Coarfa, associate professor of molecular and cellular biology at Baylor.

Such an approach would integrate epigenomics and other ‘omics,’ such as proteomics, or proteins produced; metabolomics, or metabolites present; and microbiomics, or data about present microorganisms, according to the team, which published their results recently in Aging.

At the completion of apparently successful therapy, tuberculosis patients have a nearly 3-fold increased risk of death due to unknown reasons, according to previous literature cited by the paper. Previous work by the Baylor team demonstrated that tuberculosis patients exhibited DNA hypermethylation associated with decreased immune responsiveness and that the DNA hypermethylation marks did not normalize six months after the completion of successful tuberculosis therapy.