New Study Finds Loss of Stem Cells Contributes to Premature Aging

The early aging and loss of stem cell reservoirs in adult mice is dependent on the deletion of a gene important in embryo development. The discovery was made by researchers at the Abramson Family Cancer Research Institute of the University of Pennsylvania.

Specific varieties of cancer and other disorders in humans are consequences of protein mutations that transpire during DNA damage response. Critical for this response to damaged DNA is a gene called ATR. The inaugural issue of Cell Stem Cell has published the new findings.

“The reason we’re seeing the early signs of aging in these mice is that we’re exhausting their ability to renew tissues,” says Eric J. Brown, PhD, Assistant Professor of Cancer Biology. “We believe these findings may be helpful to the aging and oncology fields since premature aging syndromes and many cancers involve the loss of DNA repair genes.”

Within three to four months, the mice used in the study began to exhibit signs of osteoporosis, graying hair, and hair loss. These were obvious characteristics of premature aging. All the symptoms occurred when the researchers deleted ATR in the adult mice tissue.

A reservoir of specific adult stem cells exists in most tissues for the function of self-renewal. Since multiple divisions lead to natural breaks in DNA, in order to preserve the integrity of the DNA, these stem cells don’t divide as frequently as other cell types. However, to replenish tissue with new cells, they are capable of rapid division when necessary.

Initially, 10 to 20 percent of cells that escaped ATR deletion were able to reconstitute tissues in the engineered mice explained Brown. But overall, the majority of mouse cells without ATR had an overwhelming amount of DNA damage and could not contribute to tissue renewal.

“Think of aging as a slow loss of stem cells, a deterioration of pools of cells that reside in each tissue type,” says Brown. We accelerated the aging process by wiping out a large fraction of these cells prematurely, in one fell swoop. Essentially, these mice start their young adulthood with two strikes against them in terms of long-term tissue maintenance, and so, they subsequently age before their time.”

Brown, first author Yaroslava Ruzankina, and Amma Asare will be using the new knowledge of how stem cells, DNA repair, and the aging process interconnect in the mouse model to discover compounds that preserve stem cells and may, consequentially, suppress aging.

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