Longevity Questions

Ser ♾️, [08.05.2025 10:22]
328. Which early cell subclone (in skin, blood, or hypothalamus) is the first to show a methylome shift after puberty, and what signaling pathways are activated at that time?
329. Which specific p53-neutral sites in the genome are safest to edit with CRISPR to reduce mTOR activation without increasing mutagenesis?
330. What is the actual annual rate of accumulation of double-strand DNA breaks in human stem cells after age 80, and where is the point at which cancer risk increases exponentially?
331. Which combinations of histone modifications (H3K27me3 + H3K9ac, etc.) provide a stable young transcriptional program in a floating experiment on human organoids?
332. How quickly are epimutations removed/corrected by artificially activating TET enzymes in aged somatic cells?
333. What minimum number of epigenetic clocks (CpG sites) must be calibrated in vivo to maintain the biological age of a 20-year-old in the blood and skin for 10 years?
334. What is the effect of targeted introduction of the CETP I405V allele on lipid profiles and inflammatory markers in middle-aged individuals for 24 months?
335. Can an inserted UAG → NC stop codon realistically block LINE-1 retrotransposition in human iPS cells?
336. What defects in the NER pathway in 120-year-old individuals can be compensated for by overexpression of XPA or ERCC1 genes without cytotoxicity?
337. At what threshold of ubiquitinated protein accumulation does the proteasome in old cells begin to irreversibly "choke"?
338. Is it possible to deliver an AAV construct encoding an artificial protease cascade that removes all proteins with a carbonylation level > 50 pmol/mg into cells?
339. Which crosslinks (e.g., iso-dehydro-decine) remain in liver proteins after an intensive glutathione reductive cycle?
340. How does the HSP70/90 chaperone network change during long-term cultivation of neuronal organoids, and is it possible to add a synthetic chaperone to restore τ protein folding?
341. How many clonal mitochondrial deletions in muscle fibers are critical for a 10% decrease in muscle strength?
342. Does nanotubule-based allogeneic mitochondria transplantation support neuronal bioenergetics without microglial activation in an aged mouse model?
343. How long can chronic AMPK activation (via metformin/SGLT2i) be maintained without disruption of sex hormones in 70+ year old humans?
344. At what precise level of mitochondrial H₂O₂ does NF-κB signaling required for immune response cease?
345. How much does synaptic transmission decrease with a 25% reduction in basal metabolic rate in primates?
346. Which two SASP factors (IL-6, IL-8, or GDF15?) are master regulators of the acute → chronic inflammatory response transition?
347. What dose and interval of Fisetin is optimal for removing senescent cells in muscle without reducing regeneration after injury?
348. Can transient expression of Yamanaka factors in senescent fibroblasts restore the cell cycle without active MYC?
349. Which set of miRNAs restores phagocytosis of macrophages in old mice to the level of young mice?
350. Which three nodal cytokines must be blocked by monoclonal antibodies to reduce CRP by 50% while maintaining vaccine response?
351. At what percentage of T cells with shortened telomeres does adaptive immunity become irreversibly dysfunctional?
352. To what extent does constant expression of osteopontin in endosteal bone marrow cells prolong the youth of the HSC niche?
353. What concentrations of GDF11 and Wnt7a should be locally maintained to fully restore muscle regeneration in 90-year-olds?
354. Is cardiomyocyte division triggered by forcibly increasing the export of nuclear Ran-GTP gradient?
355. What biomaterial and morphogens are needed to form an autonomous stem cell "factory" upon implantation under the skin?
356. Are Schwann cells and endothelial cells synchronized during joint 3-D bioprinting of the neurovascular bundle?

Ser ♾️, [08.05.2025 10:23]
357. Which microRNAs in the arcuate nucleus of the hypothalamus trigger systemic aging, and can they be inhibited by a viral antago-mir?
358. How many cycles of partial reprogramming (OSK) can the hippocampus tolerate without losing long-term memory in mice?
359. What IGF-1/insulin ratio minimizes aging markers in liver tissue without sarcopenia?
360. Will long-term activation of the motor protein KIF5 restore mitochondrial courier transport along the axons of old neurons?
361. How many moles of endoglycosidase Lysyl-Oxidase-Like 2 must be delivered to the dermis to reduce the collagen AGE crosslink by 30%?
362. What levels of YAP/TAZ activation in fibroblasts restore elasticity to the pulmonary interstitium without provoking fibrosis?
363. How does the ultimate distensibility of the aorta change after a single injection of a “smart” (pH-dependent) form of collagenase?
364. Which bacterial strains produce indole-3-propionic acid in quantities correlated with low epigenetic age?
365. Is the microbiome stabilized by monthly transplantation of a personal "bank" of cryoencapsulated gut bacteria?
366. What shift in the time of the first meal reduces the level of circulating BCAA in carriers of the PPARα L162V variant?
367. Which polymer matrix provides the oxygen-transport capacity of "artificial" red blood cells of at least 200 mm Hg?
368. Will the addition of a LAG-3 checkpoint inhibitor reduce the risk of post-senolytic relapse of latent tumors?
369. What is the VAF (variant allele frequency) threshold for DNMT3A mutations at which the probability of leukemia remains < 5% over 50 years?
370. How many telomere base pairs can be safely lengthened at a time using hTERT mRNA without activating the ALT pathway?
371. What levels of p21 expression distinguish physiological rare proliferation of 100-year-old liver cells from early neoplasia?
372. What is the minimum coverage (reads per cell) required for single-cell ATAC-seq to detect rare (0.01%) clonal epigenetic abnormalities?
373. Is it possible to build a hybrid nanoantenna-based biosensor capable of continuously measuring plasma NAD⁺ levels?
374. Which GNN (graph neural network) architectures best explain the contribution of tissue-tissue interactions to biological age?
375. What nanorobot size and charge minimize complementation and phagocytosis during long-term (> 1 year) missions in blood?
376. What models of therapy cost distribution (subscription, pay-for-results) will ensure access to ≥ 80% of the population to anti-aging technologies?
377. What is the optimal threshold of evidence (Bayes factor level) after which an anti-aging intervention can move from the clinic to the market without slowing down research?