Anti-aging drug research has homed in on senescent cells in recent years. These are damaged cells that accumulate in various tissues and organs as we get older and are known to damage adjacent cells and cause chronic inflammation associated with age-related diseases. A team of scientists has discovered a peptide that targets these cells to reverse symptoms of aging in mice. The treatment restored missing fur, improved kidney function and fitness in mice genetically engineered to rapidly age.
Many scientists have been working on strategies to find treatments that could kill senescent cells without damaging healthy ones. In 2015, a team at The Scripps Research Institute discovered two compounds selectively targeted specific groups of senescent cells. And in 2016, researchers at the Mayo Clinic trialed a compound that eliminated senescent cells in mice, resulting in an extension of median lifespan by 17 to 35 percent.
Now researchers at Erasmus University Medical Center in the Netherlands have identified a peptide that causes senescent cells to go through apoptosis, or programmed cell death. The therapy works by blocking the communication of a protein called FOXO4 with another protein, p53. It is believed that the interaction of these two proteins is what causes senescence in cells and when that communication is blocked the senescent cells self-destruct.
What makes this an important discovery is the fact that the peptide only causes cell death in senescent cells, and not healthy cells.
"FOXO4 is barely expressed in non-senescent cells, so that makes the peptide interesting as the FOXO4-p53 interaction is especially relevant to senescent cells, but not normal cells," explains senior author of the Erasmus research, Peter de Keizer.
The research involved administering the peptide to genetically engineered fast-aging mice three times a week for over 10 months. Over the course of the treatment, the researchers identified different effects manifesting in the mice. Within 10 days of starting the treatment patches of missing fur reappeared on their coats, and after three weeks the mice receiving the treatment had the ability to run twice as far as mice that hadn't received the treatment.
Biomarkers indicating healthy kidney function were also seen after one month of treatment, signaling an improvement in the animal's renal function. With almost a year of regular infusions, the research team failed to identify any obvious negative side effects of the treatment.
The team is preparing to start a human trial soon. It is still unknown whether the peptide is non-toxic in humans or whether it will result in similar beneficial effects. Still, the research into senescent cell therapy is looking promising for the future development of treatments for age-related diseases.
The proof-of-concept study was recently published in Cell.
Source: Cell Press via Science Daily