Lowered levels of stromal cell-derived-factor-1 (SDF1)—a signalling molecule found in the bloodstream—may be a factor that causes wounds in older people to heal with less scarring than in younger people, according to a study published in Cell Reports (Sept. 2018; 24(13):3383-3392.e5).
SDF1 can be found in the bloodstream and was previously shown to play a role in scar formation in the skin, liver, and lung. People produce lower levels of the molecule as they age.
Since SDF1 inhibitors already exist on the market and currently used as a treatment to mobilize stem cells, these findings can quickly be used in developing cutaneous scar prevention treatments for humans.
“This is a rare instance where aging actually improves the body’s ability to heal rather than diminishing it,” said study author Dr. Thomas H. Leung, assistant professor of dermatology at the University of Pennsylvania in Philadelphia, in a press release. “When we’re younger, we secrete more SDF1 into the bloodstream to form scars, but as we age, we lose this ability, which allows tissue to regenerate.”
Dr. Leung and his colleagues used human and mouse models in their investigation.
Researchers concluded that aging promotes tissue regeneration
and decreased scar formation in mouse ears.
Photo by Dr. Thomas A. Leung and team.
First, they pierced the ears of mice of different ages—the equivalent of a 12-year-old and a 70-year-old if converted to human years. The investigators observed that the hole closed with no scar formation in older mice, while younger mice healed with a visible scar. Then, they transferred the blood of the young mice into the older mice, pierced their ears, and found that the ears of the old mice now scarred. They concluded that the cause of the scarring must be a constituent of the blood.
With this in mind, the team then took tissue samples from young and old mice and compared their gene expression signatures. Eighty differences were identified, which were narrowed down to 13 signatures once they isolated the gene products present in the bloodstream. One of the signatures was SDF1. Considering its known links to tissue scarring, SDFI was the most promising option for the scientists. They confirmed that SDF1 was expressed in younger mice but not older.
To prove that SDF1 may be the causal factor, they created mice that lacked SDF1 in the skin. When SDF1 function was inactivated, even young mice began to regenerate skin, behaving, in this sense, like older mice.
Furthermore, researchers exchanged the blood between young SDF1-deficient mice and older mice. This time, neither mouse scarred. They also tested the theory on humans by growing human skin in the lab and injuring it with a scalpel. The human skin also exhibited an age-dependent expression of SDF1.
“Dermatologists and plastic surgeons have consistently observed that older people’s wounds heal with thinner scars than younger patients’ but until now, no one has been able to answer the question of why that’s the case,” said Dr. Leung.