First genetic glimpse of kidney offers insight into how cells grow old

STANFORD, Calif. – For the first time, researchers at Stanford University School of Medicine have examined how kidneys change at a molecular level with the passage of time. What they found suggests that all human cells age in a similar way, supporting one theory about how cells grow old.

“Until now we really didn’t know what happens when people get old,” said Stuart Kim, PhD, professor of developmental biology and genetics, who led the study that is to be published in the November 30 issue of Public Library of Science Biology. “Our work suggests that there’s a common way for all tissues to get old.”

These findings are contrary to one model for how cells age. This theory holds that because organs have different groups of molecules, they follow different pathways as they age. If this were the case then the aging kidney would look quite different on the molecular level from an aging liver.

Instead the study findings support another model, which suggests that all cells in an animal peter out in the same way. If this were true then researchers would find the same molecular differences between old and young cells from all organs.

In the study, Kim and his group compared which genes are active in kidney cells from 74 people ranging in age from 27 to 92 years. They found 742 genes that become more active as the kidney ages and 243 genes that become less active.

They then did the same experiment using different types of kidney tissue, with one sample from the outer kidney, called the cortex, and the other from the inner kidney, called the medulla. Although these two tissues are both from the kidney, they are as different in function as cells from entirely different organs. The researchers found exactly the same genes varied in old and young samples from these two tissues.

Kim said his study doesn’t suggest what factors drive the aging process, only that once it starts it follows the same path even in different organs. He added that he doubts cells wear out the same way in all animals. The reason is that until the past few centuries humans and other animals usually died before their organs had a chance to grow old, so there’s no reason for evolution to have pushed human, mice and other animal cells to deteriorate in the same way.

“Old people only exist in modern society,” Kim said. “Events that happen when a person is 80 only became common this century.” Likewise, few mice make it to two years old outside the laboratory. Kim is now studying aging mouse kidney cells to test whether they look different on a molecular level than the human kidney cells in this study.

Kim said that whatever happens once aging begins, the mechanism that kicks off the process is probably genetically determined. That’s why humans and mice, whose cells behave almost identically in a lab dish, have such dramatically different life expectancies. “The smallest genetic change can be a big change in terms of lifespan,” he said.

In addition to answering some questions about how cells age, Kim said this work could help screen kidneys used for transplant. In the study, the group found that the molecular age of a kidney matched how well that kidney filtered blood. One sample from an older person had the molecular appearance of a much younger kidney and also filtered blood like a more youthful organ.

This correlation could help screen kidneys from people older than 60 whose organs would ordinarily be rejected for transplants. Kidneys that have a youthful molecular appearance might still function well enough to be transplanted. “We can look at the kidneys that are being thrown out and parse them into those that are physiologically young and physiologically old,” Kim said.

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