Naturally, aged mice and genetically modified mice have shown evidence of improved healthspan by using anti-senescent cell therapy. Cell senescence is thought to be associated with normal aging and is protective against cancer. Researchers have found that senescent cells undergo changes in their chromatin, similar to changes in cells that are prematurely aging.
The proof of concept study is published in Cell, found that anti-senescent cell therapy might help to reverse age-related loss of fur, poor kidney function, and frailty. It is currently being tested whether the approach also extends lifespan, and human safety studies are being planned.
After a decade of investigating vulnerabilities in senescent cells as a therapeutic option to combat some aspects of aging, there has finally been some progress.
The peptide works by blocking the ability of a protein implicated in senescence, FOXO4, to tell another protein, p53, not to cause the cell to self-destruct. By interfering with the FOXO4-p53 crosstalk, the peptide causes senescent cells to go through apoptosis or cell suicide.
“Only in senescent cells does this peptide cause cell death,” says senior author Peter de Keizer, a researcher of aging at Erasmus University Medical Center in the Netherlands. “We treated mice for over 10 months, giving them infusions of the peptide three times a week, and we didn’t see any obvious side effects. 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.”
Fast-aging mice with patches of missing fur began to recover their coats after 10 days. After about three weeks, fitness benefits began to show, with older mice running double the distance of their counterparts who did not receive the peptide. A month after treatment, aged mice showed an increase in markers indicating healthy kidney function.
Senescent cell therapy is one of several strategies being tested in mice that is aimed to reverse aging or lengthening healthspan. In 2015, the Valter Longo laboratory at the University of Southern California reported that mice on a calorie-restricted diet that mimics fasting benefited from longer life, a reduction in inflammatory disease, and improved memory.
“This wave of research on how we can fight aging is complementary and not in competition,” says de Keizer. “The common thread I see for the future of anti-aging research is that there are three fronts in which we can improve: The prevention of cellular damage and senescence, safe therapeutic removal of senescent cells, to stimulate stem cells–no matter the strategy–to improve tissue regeneration once senescence is removed.”
de Keizer aims to start a company based on these findings, but in the short term, he and his group want to show that their peptide is non-toxic in humans with no unforeseen side effects. They plan to offer a safe clinical trial in people with Glioblastoma multiforme, an aggressive brain tumor, which also shows high levels of the biomarkers needed for this FOXO4 peptide to be effective.
The original source: Sciencer