Blood cells could hold the key to aging

An international team discovers that the DNA of blood cells remains stable and defines the cell age

Blood cells could be the key to aging, according to a new study from Case Western Reserve University's School of Medicine. In a study published in Aging cell, the researchers found that human blood cells have an intrinsic clock that remains stable even after a transplant. Researchers say that the clock could control human aging and could be at the origin of blood cancers.

Shigemi Matsuyama, DMV, Ph.D., a cell biologist and badociate professor of medicine at Case Western Reserve University's School of Medicine, led an international team of researchers studying the clock. The team measured cell age in transplanted blood cells from healthy donors to patients with leukemia, focusing on donor-recipient couples of very different ages.

"This study is related to the fountain of youth," said Matsuyama. "We found that young blood cells remain young in the elderly.There was no accelerated aging of young blood cells in an older human body." The Matsuyama team discovered that the opposite was also true: the blood cells of adult donors transferred to an older child. The cells retained their intrinsic age nearly two decades after the transplant.

Their intrinsic stability suggests that blood cells could spearhead human aging because they are not easily influenced by their environment, said Matsuyama.

The study showed that blood cells retain epigenetic profiles in the methylation of DNA – chemical groups attached to DNA – that can be used to calculate their age. Despite significant age differences between donor and recipient (up to age 49), the age of methylation of transplanted blood DNA reflected the donor's age, even after many years of exposure to the body of the recipient, wrote the authors. Matsuyama said: "DNA is a timekeeper of our time."

The methylation of DNA as a predictor of age was first described in 2013 by Matsuyama's collaborator on this study, biostatistician Steve Horvath, PhD of the University of California in Los Angeles. "He found the formula.The mechanism, and if the cells in the body synchronize the age of DNA methylation, was not clear," Matsuyama explained. "I am not a mathematician, I am a cell biologist, so we collaborated to study the mechanism of the epigenetic clock in an experimental system of my laboratory."

Matsuyama tested blood samples collected regularly as part of the transplant follow-up, with the help of the Case Comprehensive Cancer Center. He has expanded his sample repository via leukemia researchers from the University of Oslo, Norway, who have heard of his work at the 2016 Keystone Symposium on Aging in Santa Fe , in New Mexico. Horvath badyzed cell age with 353 distinct methylation sites found on the DNA of blood cells.

Together, the researchers provided the first experimental evidence that the aging clock of blood cells is intrinsic to cells and not defined by interactions with other types of cells in the body.

They are now working to identify mechanisms that can change the clock. "In cancer cells, the clock is broken," said Matsuyama. DNA methylation patterns are unstable in cancerous blood cells and often exhibit abnormal aging – for example, 200 or 5 years in a 50-year-old patient. "It does not correspond at all to the real age." Matsuyama warns that this is why, although it may seem attractive, he still does not recommend "therapeutic" cell infusions to try to maintain his youth.

"We do not know if blood cells serve as a master clock that could synchronize other cells, we do not know yet," he said.

Instead, the Matsuyama team seeks to understand why epigenetic age differences exist in cancer cells and how to overcome them. "It can be by activating or deactivating certain genes in cells, we can reset the clock."

Recent studies show that the age of human cell DNA can be used as a biomarker to predict the risk of age-related diseases, such as Alzheimer's disease, diseases cardiovascular, etc. Last year, Horvath and Matsuyama contributed to the publication of an article reporting that the age of DNA was significantly accelerated in progeria patients with premature aging. Matsuyama and his colleagues now have several studies under way to discover the mechanism of age-dependent DNA methylation and understand how factors such as diet, exercise and levels of Oxygen influence the epigenetic clocks.