Longevity Questions

Perpetual Prompt ♾️, [08.05.2025 21:29]
721. What frequency range of coherent oscillations of microtubules in neurons correlates with the minimum rate of DNA methylation measured by the Horvath clock, and is it possible to pharmacologically shift this range to slow down epigenetic aging?
722. What concentration of heavy water (D₂O) inside axonal microtubules is acceptable without neurotoxicity, and does isotopic substitution of protons affect the coherence time measured by terahertz spectroscopy in vivo?
723. Does the introduction of subnarcotic doses of xenon reduce the spectrum of spontaneous microtubule collapses (according to the ORCH-OR model) and does this correlate with the expression of the longevity genes SIRT1 / FOXO3 in the hippocampus of mice?
724. Is it possible to maintain NAD⁺ bioavailability at a level characteristic of the young phenotype and extend the median lifespan of rodents by >30% through optogenetic manipulation of Kir6.2 ion channels in the ependymal niche of the brain?
725. What configuration of bioelectric fields (membrane potential gradient) in the liver optimally suppresses the expression of SASP factors in aging hepatocytes, and is it possible to sustainably maintain it using non-invasive fields of variable frequency <1 kHz?
726. To what extent is the cross-linear folding of collagen I accelerated in the dermis with combined blockade of AGE receptors and inhibition of LOX enzymes at the ECM level, and how does this affect the elasticity coefficient of the skin in people aged 60+ years?
727. Can genetically modified Akkermansia muciniphila strains with an integrated spermidine cassette pathway stably colonize the human colon and reduce the clinical epigenetic “DNAmethylation pace” to ≥15%?
728. What is the effect of chronic delivery of di-indolyl-methane (DIM) in complex with exosomes on the expression of Nrf2-dependent antioxidant genes in neuronal microglial cells and on cognitive aging in a primate model?
729. Does CRISPR knockout of the LINE-1 ORF2p gene in somatic stem cells reduce the frequency of DNA double-strand breaks and increase cloning efficiency after the 40th passage in vitro?
730. Can intermittent (1×6mo) administration of the low-dose pan-senolytic FOXO4-DRI prevent sarcopenia by preserving satellite cells and increase the leg strength index in humans aged 70+ by ≥20%?
731. What is the range of peak mitochondrial ultraweak biophoton powers observed in supercentenarians >105y, and can a similar spectrum be artificially induced using a controlled photobiomodulation protocol?
732. Does restoration of Klotho-β expression via AAV therapy in cardiomyocytes reduce the incidence of valve calcification and increase left ventricular vital capacity in the presence of hypertension in aged mouse models?
733. How does PCSK9 gene deletion in glial cells affect brain lipid metabolism and lifespan in supercentenarian mouse strains on a normolipidemic diet?
734. Can low-intensity transcranial ultrasound (tUS; 300 kHz) synchronize hippocampal theta rhythm and reduce Aβ42 accumulation when administered chronically for 12 months?
735. What is the minimum number of senescent cells remaining after CAR-T senolytic therapy that allows reversion of the full SASP phenotype, and what is the threshold (in % of the initial number) for human therapy?
736. To what extent does the rate of repair of UV-B-induced DNA damage increase with the expression of PHR+MGMT photolyase in keratinocytes, and does this delay the visible chronoaging of the skin?
737. Can human thymus lifespan be extended by perfusion with PE-GF β1-reconstituted dezimbir matrix material and does this restore the naive T-cell CD4⁺/CD8⁺ ratio after 60 years?

738. What plasma level of the endogenous metabolite α-ketoisocaproate is associated with zero gain in DunedinPACE biological age over a three-year period?
739. What effect does concomitant administration of an SGLT2 inhibitor and a GDF11 mimetic have on left ventricular wall mass and VO₂max after 12 months in elderly non-diabetic patients?

Perpetual Prompt ♾️, [08.05.2025 21:29]
740. Does knocking out p16Ink4a and p19Arf genes exclusively in pancreatic β-cells reduce the risk of age-related diabetes mellitus, provided that tumor potential is prevented via p53-overdrive?
741. Can autovaccination against self-proviral HERV-K elements reduce chronic low-grade inflammation and thereby decrease the C-reactive aging rate in people >65 years old?
742. How do axial flows of tissue cerebrospinal fluid dynamics (glymphatic clearance) change after implantation of a flexible piezoelectric membrane into the cribriform plate, and does this affect the rate of tau protein clearance?
743. Is it possible to encapsulate mRNA encoding β-catenin and YAP for targeted delivery to liver cells, avoiding tumor transformation but increasing regenerative capacity after partial hepatectomy?
744. Does administration of a combined TGF-β1/Activin A inhibitor reduce the development of pulmonary fibrosis and simultaneously prolong the survival of Ercc1⁻/⁻ mice modeling accelerated aging?
745. Which parameters of a hybrid protocol diet (cyclic methionine restriction + high essential amino acid profile) optimally reduce protein succinylation in middle-aged humans?
746. How does CRISPR editing of the NADPH-quinone oxidoreductase 1 (NQO1) promoter affect oxidative stress resistance in hematopoietic stem cells and long-term erythropoietic function?
747. Is it possible to stabilize telomeric DNA without tumorigenesis by in vivo delivery of dBc-antisense against TERRA RNA only in the subclinical <4kb shortening region, and does this prolong lymphocyte immunocompetence?
748. To what extent does administration of glycomimetic sialyl-HAHA-polyethylene glycol conjugates enhance the activity of CD22 inflammation-suppressing pathways, and does this prolong the healthy lifespan of apolyprotein mice?
749. What effect does stabilization of the mitochondrial NADPH oxidative peak with cysteine ​​riboside have on skeletal muscle mitochondrial biogenesis and general aerobic fitness in aged rodent models?
750. Can synchronized cloned Wolbachia endosymbionts with an inserted pathway for the synthesis of sulfur-bearing coenzyme-Q₁₀ restore mitochondrial potential in host cells and thereby reduce the rate of accumulation of mtDNA mutations by 50% over the life cycle of a mouse?