Longevity Questions

Perpetual Prompt ♾️, [08.05.2025 20:17]
451. Who exactly is the "longevity carrier"? Which taxa (bacteria, archaea, eukaryotes) can physiologically colonize humans for ≥ 150 years without losing synthetic cassettes and beneficial phenotypes?
452. Threshold capacity of metabolites. What is the minimum daily production of key geroprotective molecules (NAD⁺-precursors, spermidine, indoles, SCFA) for a 2-3-fold slowdown in the rate of epigenetic aging?
453. Limited substrate. What nutrients should the host supply to the symbiont so that it does not resort to "energy theft", compromising its own metabolism?
454. Immunological barrier 120+. How to reprogram the innate immunity and IgA repertoire to prevent chronic "slow-burn" inflammation during half a century of microbial contact?
455. Genetic stability of cassettes. How to minimize horizontal transfer of engineered operons to other niche microbes, including pathobionts?
456. Kill-switch without auto-kill. How to embed a programmable "soft suicide" (CRISPR-kill, Aux-otrophy) in a symbiont so that the host can switch off the strain without accidental activation during fever or dietary shift?
457. Cancer safety. Can chronic symbionts increase local mutagenesis (ROS, nitrosamines) in the gastrointestinal epithelium - and how to track this before dysplasia?
458. Synthetic vs. natural microbiome. How stable is the composition of "five-six engineered strains" against exogenous invasions (Clostridioides, Candida) during antibiotic therapy?
459. Equilibrium with viruses. How does correction of the bacterial pool affect latent DNA viruses (EBV, CMV) and is it possible to simultaneously reduce their gerontological contribution?
460. The "microbe → endocrine system" axis. What percentage of circulating IGF-1/insulin/glucagon can be modulated through bacterial metabolites without systemic pharma intervention?
461. Reduction of cellular senescence. Can in situ symbionts increase the clearance of SASP-secreting cells (e.g., via NNMT inhibitors) and reduce intertissue SASP connectivity?
462. Neuro-micro-immune triad. How long can symbiont GABA/serotonin synthesis maintain cognitive reserve without developing tolerance in central receptors?
463. Secondary metabolome. What side metabolites will accumulate over 50+ years and is there a risk of their deposition in tissues (amyloids, melanoidins)?
464. Somatic DNA metabolism. Is integration of bacterial plasmids into endodermal cells of the human intestine possible over >50 years of colonization?
465. Regeneration mechanisms. How do symbiont-secreted factors (e.g., PQQ, laminin-like peptides) affect the reserve of crypt and bone marrow stem cells?
466. Host epi-control. Can methylated bacterial short DNAs be used as an "epigenetic vaccine" that rewrites the host methylome into a "young" pattern?
467. Nutrigenetics 200+. How should dietary macro-/micronutrients be tailored to the needs of an engineered consortium so as not to increase caloric content but provide substrates?
468. Geroprotector vs. reproductive capacity. Will the human population maintain sufficient fertility if bacterial signals reduce hormonal peaks?
469. Long-term testing models. Which animals (killifish, naked mole-rat) are suitable for rapid proximation of 50-60 years of human exposure?
470. Bioinformatics of failure points. Which "omic" biomarkers (metabolome, cell-free DNA, IgA repertoire) are the earliest to predict symbiont "fatigue"?
471. Horizontal transmission in the population. How to prevent unauthorized "escapade" of engineered strains into the common human ecosystem with unpredictable evolutionary consequences?
472. Regulatory perspective. Which international standards (FDA-CBER, EMA-ATMP) will apply to "live geroprotectors" and how to integrate lifelong post-market monitoring?
473. Ethical and social inclusion. Is it possible to guarantee fair access to symbiont therapy and avoid deepening social inequality in longevity?
474. Impact of antibiotics and chemotherapy.

Perpetual Prompt ♾️, [08.05.2025 20:17]
How to "restart" a consortium after courses of streptogramins, immuno-/chemotherapy drugs or transplantation?
475. Cross-tissue communication. Can symbiont exosomes enter the bloodstream and deliver miRNA/cDNA to distant tissues without the risk of microbial sepsis?
476. In vivo sensorics. How to embed a biosensing circuit (lactones, NO, ketones) into bacteria to detect inflammation locally and dynamically adjust secretion?
477. Stabilization of peptide therapeutics. What natural or artificial capsid-like proteins can symbionts use to protect stress-sensitive geroprotective factors from gastric proteolysis?
478. Biocenosis and senile skin atrophy. Can skin engineering (Cutibacterium vectors) reduce dermal senescence and maintain barrier function in people over 120 years old?
479. Production economics. How to make cGMP cheaper fermentation and lyophilization of poly-strain-cocktail to a cost of < 1 USD/dose while maintaining the genetic identity of the batches?
480. The final curvature of survival. How to find the mathematical boundary at which the increase in average lifespan by 50% due to symbionts does not run into untreatable causes of mortality (brain cancer, sudden arrhythmia, trauma)?