The Fountain of Youth isn’t a literal fountain. It’s an epigenetic pattern, a collection of methylation marks on DNA, and it keeps remarkably steady time, rather like a clockwork mechanism. Although the pattern determines our intrinsic age—as well as our susceptibility to age-associated diseases—we know little about how it might be altered. For example, it has been unclear whether the clock within each cell keeps its own time, or whether a cell’s environment interactions may cause the clock to run fast or slow.

To address this question, scientists based at Case Western Reserve University analyzed blood cells, specifically, blood cells that were provided by young donors to old recipients, or by old donors to young recipients. The scientists, led by cell biologist Shigemi Matsuyama, DVM, PhD, hoped to establish whether the clock-setting DNA methylation (DNAm) pattern is cell‐intrinsic, or whether it is modulated by extracellular cues in vivo.

“This study is related to the fountain of youth,” Matsuyama said. “We found young blood cells stay young in older people. There was no accelerated aging of young blood cells in an older human body.” Matsuyama’s team found the other direction was also true—blood cells from adult donors transferred to a child stay older.

Their inherent steadiness indicates that blood cells could be the master clock of human aging, as they are not easily influenced by their environment, Matsuyama suggested.

Details of the study appeared February 8 in the journal Aging Cell, in an article titled, “Epigenetic age is a cell‐intrinsic property in transplanted human hematopoietic cells.”

“We found that the DNAm age of the reconstituted blood was not influenced by the recipient’s age, even 17 years after hematopoietic stem cell transplantation, in individuals without relapse of their hematologic disorder,” the article’s authors wrote. “However, the DNAm age of recipients with relapse of leukemia was unstable. These data are consistent with our previous findings concerning the abnormal DNAm age of cancer cells, and it can potentially be exploited to monitor the health of HSCT recipients.”

In this study, Matsuyama and colleagues provide the first experimental evidence that the aging clock of blood cells is cell-intrinsic, and not set by interactions with other cell types in the body. They are now working to identify mechanisms that can change the clock.

“In cancer cells, the clock is broken,” Matsuyama pointed out. DNA methylation patterns are unstable in cancerous blood cells and often show odd aging—200 or 5 years old in a 50-year-old patient, for example. “It does not match at all with the actual age.” Matsuyama cautioned that this is why, although it may sound appealing, he doesn’t yet recommend “therapeutic” cell infusions to try to maintain one’s youth.

“We don’t know if blood cells serve as a master clock that could synchronize other cells. We just don’t know yet,” he said.

Instead, Matsuyama’s team is working to understand why epigenetic age differences exist in cancer cells, and how they could be overcome. “It may be by turning on or off certain genes within the cells, we can reset the clock.”

Recent studies show the DNA age of human cells can be used as a biomarker to predict the risk of age-associated diseases, such Alzheimer’s disease, cardiovascular disease, and others. Last year, Horvath and Matsuyama helped publish an article reporting that DNA age is significantly accelerated in Progeria patients who suffer from premature aging. Matsuyama and his colleagues now have several studies underway to uncover the mechanism of age-dependent DNA methylation, and to understand how factors such as diet, exercise, and oxygen levels influence epigenetic clocks.

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