Senolytics to Make the Aged Heart More Regenerative
An interesting discussion here on one the less obvious outcomes one might expect to result from a senolytic treatment to clear lingering senescent cells from aged tissues. The heart is one of the least regenerative organs in the body to begin with, but this becomes even more the case with age, as senescent cells accumulate and disrupt the normal processes of tissue maintenance and stem cell function with their inflammatory secretions. The catalog of benefits that might be realized by selectively destroying senescent cells in an old individual is far from complete at the present time, despite the scores of animal studies showing reversal of specific measures of aging and age-related disease.
"As you age, you have an increase in the number of senescent cardiac stem progenitor cells, and these have a reduced potential to proliferate and a reduced potential to differentiate. So, they're no longer able to do what we need them to do. One approach to solving the issues caused by senescent cells is the use of drugs called senolytics that target and kill them. We've used the drugs dasatinib and quercetin to eliminate senescent cells, and we've shown that when you eliminate senescent cells in an aged mouse model, you see a rejuvenation of the heart's regenerative potential. You have activation of the cardiac stem progenitor cells, cardiomyocyte proliferation, and decreased cardiac hypertrophy and fibrosis."
"We have devised these human cell co-culture in vitro systems, where we can test the effects of senescence and also the effects of senolytics on human cells. We've shown that senescent cells can impair survival and proliferation of a variety of cell types found in the heart. When we treat the co-cultures with senolytics to remove the senescent cells, we see an improvement in cell survival, proliferation, and improved angiogenesis. And we do these experiments in a human model, which is so important for us, to show translation."
Link: https://longevity.technology/senolytics-rejuvenate-the-regenerative-capacity-of-the-heart/