In mice with chemically‑induced lung scarring, a synthetic peptide called FOXO4‑DRI cleared out aging (senescent) cells, reduced scar tissue, and helped restore healthier lung cells. It seemed to target the scar‑forming myofibroblasts more than normal lung cells, suggesting a possible new way to treat lung fibrosis.
Jing. Xigang X; Jia. Shuang S; Teng. Maggie M; Day. Billy W BW; Afolayan. Adeleye J AJ; Jarzembowski...
The study shows that a peptide called Foxo4‑dri, which blocks a protein interaction that keeps damaged cells alive, can reduce the buildup of senescent (aged) cells in the lungs of newborn rats exposed to very high oxygen levels. By clearing these senescent cells, the peptide helped the lungs develop more normally, similar to other drugs that lower oxidative stress. This supports the idea that Foxo4‑dri works as a senolytic in living animals.
Bourgeois. Benjamin B; Spreitzer. Emil E; Platero-Rochart. Daniel D; Paar. Margret M; Zhou. Qishun Q...
Scientists discovered that the anti‑aging peptide FOXO4‑DRI sticks to a part of the p53 protein that’s usually floppy, and this binding helps kill old, senescent cells. The peptide works best when p53 is phosphorylated, and the study maps out exactly how the two molecules fit together.
Born. Emmanuelle E; Lipskaia. Larissa L; Breau. Marielle M; Houssaini. Amal A; Beaulieu. Delphine D;...
Removing senescent cells with the FOXO4‑DRI peptide (a senolytic) can actually make lung blood pressure problems worse by killing important endothelial cells in the lungs. In mice and rats, using FOXO4‑DRI or other senolytics increased signs of pulmonary hypertension, especially when the animals were already stressed by low oxygen or other disease triggers.
A new peptide called FOXO4‑DRI can make old, damaged cells (senescent cells) die by freeing the protein p53 to do its job. In mouse studies this cleared those bad cells and helped tissues work better, suggesting a possible way to fight aging‑related decline.
A lab-made peptide called FOXO4‑DRI, which blocks the FOXO4‑p53 interaction, was given to mice with chemically‑induced lung scarring. The treated mice showed less lung damage, lower collagen buildup, and a shift of p53 out of the cell nucleus, suggesting the peptide can slow down fibrosis.
The study shows that after radiation therapy, certain lung fibroblasts become senescent and actually help lung cancer cells resist treatment and cause lung scarring. A peptide called FOXO4‑DRI can selectively kill these senescent fibroblasts, making the cancer cells more vulnerable to radiation and reducing lung fibrosis in animal models.
Kong. Yu-Xiang YX; Li. Zhi-Shuai ZS; Liu. Yuan-Bo YB; Pan. Bo B; Fu. Xin X; Xiao. Ran R; Yan. Li L
Researchers found that a synthetic peptide called FOXO4-DRI can make scar‑forming cells (keloid fibroblasts) that are stuck in a senescent, aging‑like state die by pushing a key protein (p53) out of the cell nucleus. This reduces the number of stubborn scar cells in lab models, suggesting the peptide could help treat hard‑to‑heal scars.
van Willigenburg. Hester H; de Keizer. Peter L J PLJ; de Bruin. Ron W F RWF
Older donor kidneys have more cells that stop dividing and release inflammatory signals, which makes them more vulnerable during transplants. Removing these senescent cells with drugs (called senolytics) has been shown in mice to improve kidney function and overall health, suggesting a possible way to make older kidneys work better for transplants.
Valentijn. F A FA; Falke. L L LL; Nguyen. T Q TQ; Goldschmeding. Roel R
A recent review explains that as we get older, harmful senescent cells pile up in the kidneys and can worsen kidney health. In animal studies, a short peptide called FOXO4‑DRI can force these bad cells to die, which improves kidney function, boosts overall performance, and even extends lifespan. However, the research is still in mice, and there are no human dosing guidelines yet.
Zhang. Chi C; Xie. Yun Y; Chen. Haicheng H; Lv. Linyan L; Yao. Jiahui J; Zhang. Min M; Xia. Kai K; F...
Researchers found that a small peptide called FOXO4-DRI can kill old, malfunctioning testosterone‑making cells in the testes of aged mice, which helped the mice produce more testosterone. The peptide works by blocking a protein interaction that keeps those bad cells alive. While the results are promising, the work is still in early animal studies and not yet ready for human use.
Li. Yanqing Y; Zhang. Chi C; Cheng. Haicheng H; Lv. LinYan L; Zhu. Xinning X; Ma. Menghui M; Xu. Zhe...
A study in old mice found that a short peptide called FOXO4-DRI can kill aging Leydig cells in the testicles, lower the harmful chemicals they release, and help sperm production improve. Treated mice had better sperm quality and more active spermatogenesis, suggesting the peptide might counter age‑related male fertility loss, but the work is still limited to animal experiments.
The abstract reviews how aging works at the molecular level and lists several anti‑aging agents that are being studied, including the peptide FOXO4‑DRI, NMN, and plant compounds like curcumin and resveratrol. It notes that FOXO4‑DRI is considered a promising anti‑aging peptide but does not give new experimental results, dosing information, or safety data.
Deryabin. Pavel I PI; Shatrova. Alla N AN; Borodkina. Aleksandra V AV
Within the present study we proposed a novel approach for senolysis based on the simultaneous disturbance of the several homeostasis-maintaining systems in senescent cells including intracellular ionic balance, energy production and intracellular utilization of damaged products. Of note, we could not induce senolysis by applying ouabain, amiloride, valinomycin or NH<sub>4</sub>Cl-compounds that modify each of these systems solely. However, we found that ionophore nigericin can disturb plasma membrane potential, intracellular pH, mitochondrial membrane potential and autophagy at once. By affecting all of the tested homeostasis-maintaining systems, nigericin induced senolytic action towards stromal and epithelial senescent cells of different origins. Moreover, the senolytic effect of nigericin was independent of the senescence-inducing stimuli. We uncovered that K<sup>+</sup> efflux caused by nigericin initiated pyroptosis in senescent cells. According to our data, the higher sensitivity of senescent cells compared to the control ones towards nigericin-induced death was partially mediated by the lower intracellular K<sup>+</sup> content in senescent cells and by their predisposition towards pyroptosis. Finally, we proposed an interval dosing strategy to minimize the negative effects of nigericin on the control cells and to achieve maximal senolytic effect. Hence, our data suggest ionophore nigericin as a new senotherapeutic compound for testing against age-related diseases.
Huang. Yuzhao Y; He. Yuchen Y; Makarcyzk. Meagan J MJ; Lin. Hang H
Autologous chondrocyte implantation (ACI) is a procedure used to treat articular cartilage injuries and prevent the onset of post-traumatic osteoarthritis. <i>In vitro</i> expansion of chondrocytes, a necessary step in ACI, results in the generation of senescent cells that adversely affect the quality and quantity of newly formed cartilage. Recently, a senolytic peptide, fork head box O transcription factor 4-D-Retro-Inverso (FOXO4-DRI), was reported to selectively kill the senescent fibroblasts. In this study, we hypothesized that FOXO4-DRI treatment could remove the senescent cells in the expanded chondrocytes, thus enhancing their potential in generating high-quality cartilage. To simulate the <i>in vitro</i> expansion for ACI, chondrocytes isolated from healthy donors were expanded to population doubling level (PDL) 9, representing chondrocytes ready for implantation. Cells at PDL3 were also used to serve as the minimally expanded control. Results showed that the treatment of FOXO4-DRI removed more than half of the cells in PDL9 but did not significantly affect the cell number of PDL3 chondrocytes. Compared to the untreated control, the senescence level in FOXO4-DRI treated PDL9 chondrocytes was significantly reduced. Based on the result from standard pellet culture, FOXO4-DRI pre-treatment did not enhance the chondrogenic potential of PDL9 chondrocytes. However, the cartilage tissue generated from FOXO4-DRI pretreated PDL9 cells displayed lower expression of senescence-relevant secretory factors than that from the untreated control group. Taken together, FOXO4-DRI is able to remove the senescent cells in PDL9 chondrocytes, but its utility in promoting cartilage formation from the <i>in vitro</i> expanded chondrocytes needs further investigation.