Longevity Questions

Perpetual Prompt ♾️, [08.05.2025 20:56]
601. What combination of Akkermansia muciniphila and Butyrivibrio fibrisolvens strains needs to be stably colonized in the intestine for their total spermidine and butyrate production to be maintained at ≥30µmol/kg in plasma and to slow down epigenetic aging by ≥25% in progerian mice?
602. What is the ideal “safe” window length for partial epigenetic reprogramming of OCT4‑SOX2‑KLF4‑MYC in vivo (in days) that minimizes tumor risk while simultaneously restoring tissue transcriptome to a biological age of <30 years in adult primates?
603. How does the three-dimensional architecture of TAD clusters of satellite heterochromatin change in lymphocytes from humans 100+, and which sets of H3K9/H3K27 modifications keep it compact without reducing expression of infection response genes?
604. Is it possible to edit mitochondrial tRNA^Leu(UUR) in human hematopoietic stem cells to <5% heteroplasmy without losing cells from the HSC pool using CRISPR-b-dCas9-DddA-tox?
605. How far (≥50%) should plasma be diluted by neutral exchange plasmapheresis for SASP IL-6 and CCL11 levels to fall below the threshold that causes neuroglial activation, and how many cycles does a 70+ year old human require?
606. What threshold Ca²⁺/AMPK/ULK1 signaling profile must be maintained in hippocampal neurons for autophinib agonist-induced macroautophagy to clear ≥80% of lipofuscin without reducing LTP?
607. What ultrasound frequency and power (vMHz and mW/cm²) optimally opens the blood-brain barrier for delivery of anti-NLRP3 siRNA nanoparticles within a 5mm radius around the subventricular zone in aged rats?
608. How many cycles of cell delamination must be induced in the thymic epithelium using FOXN1-mRNA-LNP to restore cortical thymus volume to adolescent values ​​in 18-month-old mice, and how does this affect TCR diversification?
609. Which punctate composition of the lipid layer of nanoparticles (ω-3:ω-6:DSPC) ensures maximum selectivity for the delivery of dual senolytic load (navitoclax+siBCL-xL) to p16^Ink4a⁺ liver cells upon intravenous administration?
610. Is it possible to achieve a stable reduction in the antigen load and a reverse shift in the immune age of the CD8⁺ pool (according to KLRG1 expression) in people aged 60–70 years using triple vaccination with CMV-ΔUL138-mRNA?
611. How effective is simultaneous punctate activation of TERT and the proteostatic HSF1 (via CRISPR-SAM duplex) in type II alveolocytes for restoring telomeres and reducing the risk of idiopathic pulmonary fibrosis in old mice?
612. What proportion of the DNMT3A-R882H driver clone must be deleted with the ABE8e base editor to arrest clonal hematopoiesis progression and reduce CHD risk by ≥30% in the Ldlr-/- mouse model?
613. How does chronic activation of AQP4 perivascular polarity by low-dose melatonin alter glymphatic flow rate (µl/min) in 24-mo rats, and will this reduce cortical p-tau accumulation?
614. Can synthetic exosomes carrying siRNA against LINE-1 ORF2 reduce cytoplasmic L1-cDNA intermediates in aged fibroblasts to young control levels (<50 copies/cell)?
615. What is the effect of injection of fibroblast-specific miR-29a mimetics (via AAV-DJ) on collagen cross-linking and dermal stiffness (kPa) in a 65+ year old human for 12 months?
616. What is the methylation profile of CpG islands in the promoters of DNA repair genes (XPC, OGG1, RAD50) as a marker of the “biologically 30-year-old” state, and can it be restored with the HDAC6 inhibitor ricolinostat?
617. How fast (ns) and with what sensitivity (ppm) can NV diamond quantum sensors detect ROS peaks in muscle mitochondria in situ, and is it possible to deliver the antioxidant peptide SS-31 in real time?
618. What is the optimal combination of IL-7, stem cell factor, and NOTCH ligand DLL4 in a 3D bioreactor to restore the rate of de novo generation of iPSC-derived naive T cells to 80% of neonatal thymus levels?

Perpetual Prompt ♾️, [08.05.2025 20:56]
619. How long (per day) should GSK-3β inhibition be maintained in the cerebellum to stimulate Bergman cell proliferation without the risk of medulloblastoma in the ataxia-aging-mouse model?
620. What volume of perfluorocarbon emulsion (ml/kg) should be administered before hyperbaric oxygenation to improve oxygen diffusion into ischemic tissues in aged patients without oxidative stress?
621. What is the threshold ratio of α-keto to β-hydroxy forms of BHB in plasma that activates the SIRT3-dependent mitochondrial detoxification transcript, and can it be achieved by diet alone?
622. Can the myeloid shift in the bone marrow of aged mice be suppressed by expressing miR-125b from a lentivector only in the ossified osteoblast niche, and how does this affect B-cell pool reconstitution?
623. What is the histospecific dose of the β-secretase inhibitor LY-3372993 that needs to be delivered via intranasal gspruce quarry to reduce CSF Aβ42/40 by 50% without affecting peripheral Notch signaling?
624. Is activation of the mechanoreceptor PIEZO1 by short magnetic pulses (Hz, mT) sufficient to increase blood flow by 20% in sarcopenic 24-month-old mice and stimulate muscle protein synthesis?
625. How does clusterin and chaperone-mediated autophagy transcript expression change after 8 weeks of sensory stimulation (tVNS) in 60+ volunteers and does this correlate with a decrease in bioage according to DunedinPACE?
626. What level of stability (t½/day) should a synthetic circular RNA encoding nephthuluin depeptidase have to stably cleave AGE-modified albumin in human plasma?
627. How many repeats of the GDF11 gene under the control of an endogenous promoter can be safely prime edited into the muscle genome to maintain plasma GDF11 at 0.3–0.5ng/ml without sarcopenia?
628. What is the minimum threshold of NNMT enzyme suppression in the liver (by activity, %) required to increase systemic NAD⁺ levels to ≥60µM in aged monkeys?
629. Can pericyte density in the hippocampus of aged mice be restored by local release of PDGFRβ agonists from a hydrogel, and will this improve learning speed in the Morris test?
630. Which combination of microfluidic biomarkers (cf-mtDNA fragments, 8-Oxo-dG, GDF15) in capillary blood gives an error of ≤3 years in estimating “instantaneous” biological age and allows monitoring the effect of each of the above interventions?