Human blood cells have an intrinsic clock that remains steady even after transplant, and could control human ageing as well as underlie blood cancers. The study, published in the journal Aging Cell, measured cellular age in blood cells transplanted from healthy donors to leukemia patients, focusing on donor-recipient pairs of very different ages.
“This study is related to the fountain of youth,” said Shigemi Matsuyama, an associate professor at Case Western Reserve University in the US. “We found young blood cells stay young in older people. There was no accelerated ageing of young blood cells in an older human body,” Matsuyama said.
The team found the other direction was also true — blood cells from adult donors transferred to a child stay older. The cells retained their intrinsic age nearly two decades after transplant. Their inherent steadiness suggests blood cells could be the master clock of human aging, as they are not easily influenced by their environment, Matsuyama said.
The study showed blood cells retain epigenetic patterns in DNA methylation — chemical groups attached to DNA — that can be used to calculate their age. Despite substantial age differences between donor and recipient (up to 49 years), the DNA methylation age of transplanted blood reflected the age of the donor, even after many years of exposure to the recipient’s body, researchers said.
“DNA functions as a timekeeper of our age,” said Matsuyama.
He tested blood samples collected regularly as part of transplant monitoring, with help from the Case Comprehensive Cancer Center. Steve Horvath of the University of California, Los Angeles, crunched cellular ages using 353 distinct methylation sites found on blood cell DNA. The researchers provided the first experimental evidence that the ageing 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 said.
DNA methylation patterns are unstable in cancerous blood cells and often show odd ageing — 200 or 5 years old in a 50 year old patient, for example.
“It does not match at all with the actual age,” Matsuyama said.
Matsuyama cautions that this is why, although it may sound appealing, he does not 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 synchronise other cells. We just don’t know yet,” he said.
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,” he said.