Longevity Questions

Perpetual Prompt ♾️, [08.05.2025 20:39]
511. What are the molecular “trigger” signals that cause a single precancerous cell to transition into a clinically significant tumor in humans >120 years old, and is it possible to block these signals without suppressing tissue regeneration?
512. Which epigenetic clock most accurately predicts an individual’s risk of ultra-rare sarcomas after 100 years old, and how can methylome intervention reduce this risk?
513. How many clonal mutations does a liver stem cell “safely” accumulate before the probability of cancer exceeds 10⁻⁶ per year, and what editing tools can be used to maintain this limit?
514. Is it possible to create a CRISPR guide biosensor network in the body that will autonomously cut out non-canonical retrotransposon insertions before they are oncogenically expressed?
515. What set of circulating microRNAs serve as a universal early marker of brainstem gliomas in older adults, and how much earlier does it rise above baseline on MRI?
516. Can vaccination with personalized neoantigens once every 5 years maintain immune surveillance at the level of a 30-year-old without the risk of autoimmunity?
517. What is the minimum number of B7-H3-programmed CAR-T cells needed for prophylactic “immunosanitation” of brain micro-foci in 120-year-olds to reduce the overall risk of DIPG-like gliomas by >90%?
518. Are there lipophilic senolytics that safely penetrate the blood-brain barrier and selectively remove SASP-state astrocyte stem cells before they become malignant?
519. What ratio of α-ketoglutarate to fumarate in CSF correlates with suppression of onco-metabolite-dependent IDH mutations in people over 100 years of age?
520. Can the RNA-guided ADAR-editing system in vivo be used to reverse TP53 mutations while preserving the cells that are the source of regeneration?
521. How does the microbiome of cerebral meningeal lymphatic vessels change after 90 years of age, and does its artificial rejuvenating transplant affect the risk of meningeal sarcomas?
522. Does regular periodic plasmapheresis exchange degrade mutagenic metabolites (e.g., methylglyoxal) faster than they are formed in super-long-lived individuals, and is this sufficient to prevent DNA glycation?
523. Which set of small molecules can simultaneously activate the NRF2 response and suppress NF-κB-induced inflammation without increasing resistance of future tumors to therapy?
524. How deep can Yamanaka-based “reprogramming” (OSKM-pulses) be carried out in midbrain neurons without causing tumor transformation, and how can this be tested in situ?
525. What limiting amino acids in the diet of super-centenarians are critical for inhibiting mTORC1-dependent growth of latent tumors, and can the same effect be achieved pharmacologically?
526. What is the cumulative risk of heart cancer (angiosarcoma) after cardiac regeneration using hiPSCs, and what genetic “safety gates” are needed for absolute biosafety of cell therapy?
527. Is it possible to model “stochastic bursts” of the oncogenic MAPK signaling network in human cells on organoids in order to test combo inhibitors in advance for tumor prevention?
528. What is the optimal telomere lifetime in intestinal crypt stem cells that maintains a balance between cancer prevention and regeneration after 100 years?
529. Are there universal xenonucleases capable of removing integrated DNA viruses (HBV, HHV-6) from the hepatocyte genome without double-strand breaks, thereby reducing the long-term risk of hepatocellular carcinoma?
530. How do implantable “smart” biopolymer matrices with controlled release of IL-15 and IL-12 affect the long-term maintenance of antitumor NK cells in the elderly?
531. Can regular in vivo blockade of LINE-1 reverse transcription with RT inhibitors reduce the overall somatic mutational burden without toxicity to neurogenesis?
532. How much does deep hypothermia (32°C) once a month for 48 hours slow down the accumulation of DNA damage in bone marrow stem cells in humans over 100 years old?

Perpetual Prompt ♾️, [08.05.2025 20:39]
533. What are the limits of “tuning” the mitochondrial genome through allotopic expression to eliminate age-associated mutations without the risk of tumor-induced metabolic restructuring?
534. What is the contribution of latent neuroendocrine tumors to the main increase in mortality among centenarians >110 years old, and is it possible to implement screening at the level of single-cell metabolic profiles?
535. Is it possible to use in situ bioprinting of lymphatic vessels to enhance immune drainage of the brain and prevent tumor foci after 90 years?
536. What is the minimum editing of the HMGB1 and S100A9 promoters necessary to attenuate chroninflammasome-dependent carcinogenesis without blocking DNA repair?
537. What rate of thymus reconstruction (e.g. via FOXN1 overexpression) is safe: at what proportion of “new” thymus does the risk of T-cell lymphomas increase?
538. Is it possible to create to produce adaptive nano-immunoconjugates that, after the first contact with the tumor, reconfigure and switch to similar variants of immune bias without re-infusion?
539. Which cationic lipopeptides are able to selectively destroy membranes of cells expressing CD47-“don’t eat me”, without affecting normal cells in people over 120 years old?
540. How deep is the suppression of growth hormone (via GHRH-antagonist) necessary to minimize the oncogenic stimulus of IGF-1, while preserving muscle mass and neurogenesis in long-livers?