Research reveals how senescent cells might be an underlying reason behind kidney harm

A examine in mice by researchers at Georgetown Lombardi Complete Most cancers Middle has discovered that stress and tissue harm initiated by angiotensin II, a molecule that’s identified to extend blood strain and stiffening within the linings of blood vessels, results in mobile senescence, a course of by which a cell ages and completely stops dividing however doesn’t die. Importantly, when the researchers eradicated senescent cells from the mice, tissues returned to a traditional state despite a continued infusion of angiotensin II.

The findings seem in Frontiers in Cell and Developmental Biology on December 8, 2021.

We have identified that angiotensin II can result in hypertension and mobile harm, however our findings present that continual, stress-induced harm on account of barely elevated blood strain might be diminished by eliminating senescent cells. By stopping the dangerous results of angiotensin II, we revealed a novel mechanism for eliminating senescent cells that would doubtlessly be used to develop focused medicine to get rid of these cells.”


Irfan Khan, MD/PhD candidate, Tumor Biology program, Georgetown College and first creator

The researchers selected angiotensin II because the software to finest induce continual stress as a result of they may regulate its administration and induce a measured stress stage just like that seen in individuals who see a gradual rise in blood strain over a lifetime. This stress usually leads to much less flexibility within the lining of blood vessels, which in flip results in larger blood strain. The researchers found that these results are notably pronounced within the kidneys and never within the mind or lungs, which is what they anticipated after they began their experiments.

“We can provide folks angiotensin decreasing medicine to deal with their hypertension. However they need to be given repeatedly for a lifetime and will should be mixed with different medicine to enhance their efficacy. There’s a urgent want to deal with the intense systemic results of hypertension and provide you with novel remedies to keep away from or reverse harm to the kidneys,” says Anton Wellstein, MD, PhD, professor of oncology and pharmacology at Georgetown Lombardi and corresponding creator for this text. “Primarily, we’re constructing the organic foundation for a brand new therapeutic method to deal with the senescence side of illness that has principally been unexplored and untreated. Eliminating senescent cells with a tolerable, short-term remedy may doubtlessly alleviate continual heart problems and cut back the necessity for a lifetime of remedy.”

The researchers do not suppose anti-senescence medicine are going to be the fountain of youth, however they hope to have the ability to reverse some untimely tissue harm. “A senescence drug would in all probability be a really short-term therapy, perhaps just some days to 2 weeks,” Wellstein says. “Reasonably than continually attempting to dampen down hypertension, we suggest eliminating the senescent cells so {that a} doctor may extra simply deal with the first causes.”

Along with Khan and Wellstein, the opposite authors from Georgetown embody Marcel O. Schmidt, Bhaskar Kallakury, Sidharth Jain, Shaunt Mehdikhani, Moshe Levi, Margarida Mendenoca, William Welch, Anna T. Riegel and Christopher S. Wilcox.

The authors declare that the analysis was performed within the absence of any industrial or monetary relationships that might be construed as a possible battle of curiosity.

The analysis was supported by NIH grants P01 HL-68686 and F30 CA243357-01 in addition to grants from the Hypertension Basis and Georgetown College Institutional Funds.

Supply:

Georgetown College Medical Middle

Journal reference:

Khan, I., et al. (2021) Low Dose Persistent Angiotensin II Induces Selective Senescence of Kidney Endothelial Cells. Frontiers in Cell and Developmental Biology. doi.org/10.3389/fcell.2021.782841.

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