Ver, longevity was extended by metformin administration only in Caenorhabditis elegans, reviewed by [195], and in only one particular of the tested strains of mice [196]. An comprehensive evaluation by Tseng [197] summarized the effects of metformin on male reproductive overall health, particularly on erectile dysfunction, steroidogenesis, and spermatogenesis (showing 2-Methylbenzaldehyde Purity & Documentation advantageous effects on all concerns, mostly in animal models). Even so, none of your studies wereCells 2021, 10,15 ofperformed in aged animals or aged males. We are able to only conclude that not adequate investigation on this topic has been published; therefore, there are many opportunities to add towards the existing sources of anti-aging therapies in testicular aging. Collectively, the results of the interventions that inhibit nutrient-sensing pathway are somewhat counterintuitive and remind us that particular attention has to be provided to identifying testicular responses to any anti-aging therapy that was created on the basis of its effects on extra-gonadal tissues. 3.four. Phenolic acid MedChemExpress Senolytics and Senomorphics One particular from the hallmarks of aging is an increased variety of senescent cells which secrete many different bioactive things referred to as senescence-associated secretory phenotype (SASP) [198,199]. Targeting senescent cells has lately emerged as a therapeutic target for treating age-related diseases. Within this context, senolytics are compounds that selectively and actively get rid of senescent cells by inducing apoptosis, whereas senomorphics are compounds that suppress SASP by targeting pathways like p38 MAPK, NF-B, IL-1, mTOR, and PI3K/AKT, without the need of inducing apoptosis. Some of these compounds happen to be classified as calorie restriction mimetics as well [179]. The first generation of senolytic drugs involve distinctive compounds including Dasatinib, Quercetin, Fisetin, Navitoclax, Curcumin, Luteolin, and FOXO4-related peptide, amongst other folks [199]. Several of those are naturally occurring flavonoids, as soon as generally known as vitamin P, commonly discovered in various types of herbs, vegetables, and fruits. We are going to only refer to those compounds that have been employed to assess prospective helpful effects on testicular senescence/aging. However, senomorphics include things like polyphenols for example Resveratrol and Apigenin, Metformin, Cortisol/Corticosterone, Wogonin, Kaempferol, and NDGA [200]. The effective actions of numerous of these plyphnenols on testicular steroidogenesis happen to be reviewed by Martin and Touaibia [201]. Inside a current study, Hamza et al. [113] have developed a D-gal-induced aging mouse model. Applying this model, the authors showed that everyday intraperitoneal administration of Quercetin (20 mg/kg) or Resveratrol (20 mg/kg) for 30 days drastically decreased testicular lipid peroxidation and elevated antioxidant enzymes activities (Catalase, Glutathione reductase). In aged Leydig cells, there was also an up-regulation of Cox2 expression plus a reduction in StAR gene expression and testosterone production [121]. Having said that, incubation of aged Leydig cells in the presence of a Cox2 inhibitor can restore testosterone production. Interestingly, flavonoids which include Luteolin [202], and Apigenin [203] can promote StAR expression and steroidogenesis by inhibiting Cox2-dependent signaling in in vitro cell cultures. Additionally, helpful effects of Resveratrol following the exposure to different toxic agents has been reviewed by Pasquariello et al. [204] and are beyond the scope of this assessment since these reports were not conducted in aging experimental animals. Curcumi.