Our environment can impact our health on the most fundamental level. It can influence our genes by altering how our genes are read and expressed. This concept — known as environmental epigenetics — has transformed the way that scientists look for links between environmental exposures and disease. For example, Harvard researcher Bernardo Lemos, Ph.D., has focused his research on a single organelle that sits within the cell’s nucleus called the nucleolus.
Lemos is an associate Professor of Environmental Epigenetics at Harvard T.H. Chan School of Public Health. (Photo courtesy Bernardo LemosHis Mar. 30 NIEHS Keystone Science Lecture, Lemos explained how the study of this “tiny nucleus” is yielding insights into aging, carcinogenesis, and chronic diseases.
“It’s a really rich organelle,” he said. “And from a basic biology perspective, it’s where the inspiration for my lab resides.”
Tiny nucleus
The nucleolus is made up of an array of genomic segments known as ribosomal DNA (rDNA), which encode the machinery needed to synthesize all the body’s proteins. Lemos believes that rDNA has a high degree of environmental sensitivities and could be used to provide biomarkers for aging and environmental exposures.
Lemos explained that aging is affected by the environment. This is one of the most important known risk factors in predicting disease and death. Multiple studies have shown that aging — and the chronic diseases that come with it — can be accelerated by exposure to environmental toxicants and slowed by a relatively simple intervention: cutting calories by 20%.
“As we learn more about environmental exposures, we will likely find how exposures drive aging in the opposite direction, that is, accelerate aging,” Lemos said.
A false color transmission electron microscope image showing the cell’s nucleus (green) and nucleolus (dark blue), a structure made up of rDNA. Jose Luis Calvo/Shutterstock.His lab discovered that specific methylation patterns in rDNA can serve as an evolutionarily conserved “clock” of biological aging. Lemos demonstrated that this clock was conserved among mice, humans, and other mammals. He found that the epigenetic clock was responsive in response to changes in the environment. When his team assessed mice and rats on a calorie restricted diet, the rodents’ clocks slowed down.
Heavy metals
NIEHS is currently funding Lemos to study how exposures to a specific chemical in the environment are affecting human health. Hexavalent chromium affects rDNA. Hexavalentchromium, a form of the metallic element chromemium, has been shown to cause lung carcinoma. As part of his study, Lemos exposed bronchial epithelial cells — which act as the interface between the external environment and the lungs — to various doses of hexavalent chromium for 24 hours. Then he tracked changes in genome-wide gene expression for seven days.
Shaughnessy said Lemos’s research translates basic scientific understanding into public health with the goal of characterizing the susceptibility of individuals to the effects of environmental exposures. (Photo courtesy Steve McCaw/NIEHS).He discovered that environmental exposure affected the nucleolus, triggering widespread and persistent expression as well as DNA methylation changes in thousands more genes.
“Where do we think that responsiveness of gene expression is coming from?” Lemos said. “We think, fundamentally, it is coming from the organization of the epigenome.”
Lemos was hosted at Daniel Shaughnessy Ph.D., a NIEHS Exposure, Response, and Technology Branch health science administrator.
“Bernardo’s research on the effects of environmental stress on ribosomal DNA, together with his findings on methylation patterns of rDNA genes as a biological clock, is truly innovative,” said Shaughnessy. “[The methylation patterns] have the potential for serving as informative biomarkers of the effects of the environment on aging and disease risk.”
Microplastics
Lemos also studied the epigenetic level. MicroplasticsThese tiny pieces of plastic can now be detected in the surrounding environment. Lemos described how his lab has examined gene expression in mice that have been exposed to this material. They found changes in gene expression that were involved in a variety biological processes, including oxidative reaction, lipid metabolism and immune response.
Lemos stated that he would like to investigate the effects of microplastic contamination in specific communities in the future and is open for collaboration with anyone with relevant expertise.
“All of the work that I have presented — even the work that was not directly funded by NIEHS — would not have been possible without the support of the institute,” said Lemos. “For that, I am truly grateful.”
Citations:
Lou J, Yu S, Feng L, Guo X, Wang M, Branco AT, Li T, Lemos B. 2021. Human cells are susceptible to environmental induced ribosomal instability (rDNA) from hexavalentchromium. [Cr (VI)]. Environ Int 153:106525.
Wang M, Lemos B. 2019. The clock of biological aging is a clock that Ribosomal DNA has evolved to preserve. Genome Res 29(3):325−333.
Zhang Y, Wolosker MB, Zhao Y, Ren H, Lemos B. 2020. Exposure to microplastics cause gut damage, locomotor dysfunction, epigenetic silencing, and aggravate cadmium (Cd) toxicity in Drosophila. Sci Total Environ 744:140979.
(Marla Broadfoot, Ph.D. is a contract author for the NIEHS Office of Communications and Public Liaison.
