Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.

With the increase in life expectancy, aging has emerged as a significant health concern. Due to its various mechanisms of action, cardiometabolic drugs are often repurposed for other indications, including aging. This systematic review analyzed and highlighted the repositioning potential of cardiometabolic drugs to increase lifespan as an aging parameter in animal studies and supplemented by information from current clinical trial registries. Systematic searching in animal studies was performed based on PICO: "animal," "cardiometabolic drug," and "lifespan." All clinical trial registries were also searched from the WHO International Clinical Trial Registry Platform (ICTRP). Analysis of 49 animal trials and 10 clinical trial registries show that various cardiovascular and metabolic drugs have the potential to target lifespan. Metformin, acarbose, and aspirin are the three most studied drugs in animal trials. Aspirin and acarbose are the promising ones, whereas metformin exhibits various results. In clinical trial registries, metformin, omega-3 fatty acid, acarbose, and atorvastatin are currently cardiometabolic drugs that are repurposed to target aging. Published clinical trial results show great potential for omega-3 and metformin in healthspan. Systematic Review Registration: crd.york.ac.uk/prospero/display_record.php?RecordID=457358, identifier: CRD42023457358.

Comparative Neuroprotective Effects of Moringa oleifera Seed Oil and Aqueous Extract on Cognitive Functions on a High-Fat, High-Fructose Diet Mice: Focus on Senescence Markers.

Several studies have demonstrated that Moringa oleifera (MO) has different pharmacological properties, including neuroprotective effects. However, the role of MO in preventing brain impairment in high-fat, high-fructose diet (HFFD) remains unknown. This study aimed to investigate the neuroprotective effects of MO leaves aqueous extract (MOE) and moringa seed oil (MOO) against brain impairment in mice with HFFD. Twenty-eight male mice were randomly divided into four groups: normal diet, HFFD, HFFD + MOE 500 mg/kgBW, and HFFD + MOO 2 mL/kgBW. Cognitive function was assessed using the Y-maze and novel object recognition (NOR) tests. The p16, p21, and BDNF expressions were analyzed using the RT-PCR method. Senescence-associated beta-galactosidase (SA-ß-gal) staining in the brain was also performed. The results showed that administration of MOE or MOO could increase the percentage of alternation and recognition of new objects, prevent the increase of p16 and p21 expression, and ameliorate SA-ß-Gal activity in the brain. MOO, but not MOE, increased BDNF expression in senescence brains isolated from HFFD mice. The findings indicate that MOO and MOE possess neuroprotective properties, with MOO demonstrating a greater ability to inhibit the brain senescence process compared to MOE.

The efficacy and safety of first-line anti-seizure medications as substitution therapy for children with drug-resistant epilepsy: a randomized controlled trial protocol.

Although many anti-seizure medications (ASMs) are available, treatment failure, known as drug-resistant epilepsy (DRE), still occurs in around 30% of children with epilepsy. Second-line ASMs are usually used as substitution therapy in DRE to control seizures, although international consensus is not available yet. Previous studies focus on comparing the ASMs, whether as add-on or substitution therapy, mainly conducted in newly diagnosed epilepsy. However, the study that investigated first-line ASMs as substitution therapy compared to second-line ones, particularly among DRE children, is still lacking. A randomized controlled trial (RCT) enrolling 102 participants, aged 1-18, at three referral hospitals in Indonesia will be conducted, dividing them into intervention and control groups. The intervention group will be treated with first-line ASMs as the substitution therapy, while the other in the control group will get second-line ASMs. The primary outcome measure is the proportion difference of responders between groups who get first-line and second-line ASMs in 14 weeks of intervention. Clinical trial registration: ClinicalTrials.gov, identifier NCT05697614.