Comprehensive review of bioregulator peptides including Vesugen and their epigenetic mechanisms.

Short peptides regulate sirtuin 1 levels and protect vascular tissue from aging.

Vesugen enhances MSC proliferation and reduces senescence markers in stem cells.

Landmark discovery paper identifying MOTS-c as a 16-amino-acid peptide encoded by mitochondrial DNA. Prevented age-dependent and high-fat-diet-induced insulin resistance and obesity in mice via AMPK activation in skeletal muscle.

MOTS-c rapidly translocates to the nucleus within 30 minutes under metabolic stress in an AMPK-dependent manner, where it interacts with stress-responsive transcription factors including NRF2 and ATF7 to regulate nuclear gene expression.

Exercise induced an 11.9-fold increase in skeletal muscle MOTS-c. MOTS-c enhanced physical performance across age groups and improved muscle homeostasis in aging mice.

4-8 weeks of voluntary running increased MOTS-c protein expression ~1.5-5-fold in rodent skeletal muscles, sustained for 4-6 weeks of detraining. Single dose improved acute exercise performance.

MOTS-c significantly alleviated hyperglycemia, improved insulin sensitivity and glucose tolerance, and reduced birth weight and offspring death in a gestational diabetes mouse model.

Seminal review establishing that NAD+ decline is central to aging, driving defects in sirtuin-mediated nuclear and mitochondrial functions and resulting in age-associated pathologies.

Randomized crossover trial showing NR (1000 mg/day for 6 weeks) is well tolerated and effectively elevates NAD+ in healthy middle-aged and older adults, with preliminary evidence for reduced blood pressure and arterial stiffness.

First human clinical trial showing NMN (250 mg/day for 10 weeks) increases skeletal muscle insulin signaling and sensitivity in overweight/obese postmenopausal women with prediabetes.

Comprehensive review of NAD+ metabolism during aging, detailing how senescent cells drive NAD+ decline via CD38+ macrophage activation and outlining therapeutic restoration strategies.

Meta-analysis of 8 RCTs (342 adults) found NMN significantly elevates blood NAD+ levels, but short-term supplementation (250-2000 mg/d) did not show significant improvements in glucose control or lipid profile in the general population.

NR was well tolerated and significantly increased blood NAD+ concentrations in older adults with MCI. Global methylation analyses indicated modest NR-associated reduction in epigenetic age by PhenoAge and GrimAge clocks.

Ovagen (EDL) is a tripeptide bioregulator with effects on liver and GI tract.

Di- and tripeptides are transported via PEPT1/PEPT2, explaining tissue-specific targeting.

Short peptides reduce long-term fibrosis in liver tissue through gene expression regulation.

Pancragen normalized insulin and C-peptide levels, suggesting recovery of disturbed glucose tolerance in old animals.

KEDW directly interacts with DNA and regulates pancreatic gene expression.

Pancragen affects pancreatic cell differentiation during aging process.

Pancragen shows promise for correction of metabolic disorders in elderly people.

PNC-27 binds membrane-bound HDM-2, inducing pore formation and cancer cell necrosis while sparing normal cells.

PNC-27 also enters cancer cells and disrupts mitochondrial membranes.

PNC-27 induces necrosis of K-562 leukemia cells lacking p53 through p53-independent pathway.

PNC-27 binds HDM-2 in p53 peptide-like structure, induces selective membrane-pore formation leading to cancer cell lysis.

Phase I/II trial in 36 patients showed dose-dependent improvement in 6-minute walk test (64.5m vs 20.4m placebo at highest dose) after 5 days of treatment with excellent safety profile.

IV infusion in heart failure patients showed significant decrease in left ventricular end-diastolic volume (-18 mL, P=0.009) and end-systolic volume (-14 mL, P=0.005) at the highest dose.

8 weeks of SS-31 (3 mg/kg/day) in aged mice reversed age-related decline in mitochondrial ATP production, restored redox homeostasis, and significantly increased treadmill endurance.

40mg daily in Barth syndrome patients. Primary endpoints not met at 12 weeks, but open-label extension showed cumulative 96.1m improvement in 6MWT at 168 weeks (P=0.003) with sustained fatigue improvements.

Phase 3 trial (218 patients) did not meet primary 6MWT endpoint overall, but post-hoc analysis showed improvement in patients with nuclear DNA variants. Well-tolerated with mild-to-moderate adverse events.

Comprehensive review covering PROGRESS-HF, TAZPOWER, MMPOWER-3, and ReCLAIM trials. Highlights elamipretide’s unique cardiolipin-binding mechanism and broad therapeutic potential across mitochondrial diseases.

FOXO4-DRI restored fitness, fur density, and renal function in aged mice using 5 mg/kg IP, 3 doses on alternate days. Well-tolerated under therapeutic conditions.

Self-experimenters have translated the mouse protocol to ~25 mg per injection subcutaneously, 3 doses every other day, for 75-100 mg total per treatment cycle.

FOXO4-DRI improved testicular microenvironment and testosterone secretion by clearing senescent Leydig cells.

Removed >50% of senescent chondrocytes without affecting healthy early-passage cells.

Structural analysis revealed FOXO4-DRI binds disordered p53TAD2, forming transiently folded complex.

21 PD subjects randomized to IV glutathione 1,400 mg or placebo 3x weekly for 4 weeks. Well tolerated with no safety concerns. Preliminary data suggested possibility of mild symptomatic effect.

13-week liposomal glutathione supplementation in HIV-infected individuals resulted in significant increases in plasma Th1 cytokines IL-12 and IFN-γ, restoring immune response.

Narrative review concluding glutathione has potential as a depigmenting agent. Oral supplementation shows significant but variable melanin reduction. IV use associated with safety concerns including anaphylaxis.

Comprehensive review establishing glutathione’s roles in antioxidant defense, nutrient metabolism, regulation of gene expression, DNA/protein synthesis, cell proliferation and apoptosis, immune response, and protein glutathionylation.

Humanin overexpression extends lifespan in C. elegans; HNG treatment improves metabolic healthspan in middle-aged mice; levels higher in centenarian offspring.

Comprehensive review of humanin’s neuroprotective effects in Alzheimer’s and Parkinson’s disease models.

Review of mitochondria-derived peptides including humanin and their roles in aging and metabolic health.

Hashimoto et al. cloned humanin from Alzheimer’s patient brain; demonstrated protection against amyloid-β toxicity.