Longevity Questions

Perpetual Prompt ♾️, [08.05.2025 14:46]
378. Which two or three SASP factors (e.g. IL-6, IL-8, GDF15) make a decisive contribution to the transition of the acute inflammatory response to chronic "inflamm-aging" in people over 60 years old?

379. How do SASP factors IL-6, IL-8 and GDF15, through their specific receptors and second messengers, maintain permanent activation of the transcription factor NF-κB in macrophages?

380. How does chronically activated NF-κB signaling reprogram the epigenome of innate immunity and fix the long-term pro-inflammatory phenotype in the elderly?

381. Is it possible to develop a systemic therapy that can break the epigenetic loop of chronic inflammation-aging while maintaining a full acute antimicrobial response of the body?

382. What percentage of glucosepano and other AGE cross-links in aortic collagen is associated with a loss of vascular wall elasticity of more than 30%?

383. Is an enzyme that specifically degrades glucosepano cross-links able to remove AGE cross-links in aortic collagen without damaging intact collagen and endothelium?

384. What signaling pathways (e.g. TGF-β, YAP/TAZ, MMP regulation) activate the synthesis and correct folding of new “young” collagen after enzymatic cleavage of AGE cross-links?

385. Can quarterly therapy targeting AGE cross-links maintain arterial and pulmonary elasticity at the level of people <40 years for the next 50 years?

386. Which key niche factors of hematopoietic stem cells (CXCL12, ANGPT1, SCF, osteopontin) decrease earliest and most significantly in the bone marrow after 80 years?

387. Does local expression of CXCL12, ANGPT1, SCF and osteopontin in the bone marrow restore full trilineage differentiation of blood in aged animal models?

388. How does the action of CXCL12, ANGPT1, SCF and osteopontin on the stem niche affect the frequency of clonal hematopoiesis (CHIP) and the risk of leukemia in old age?

389. How realistic is it to create a subcutaneous organoid that mimics a bone marrow niche and can provide reserve hematopoiesis and tissue regeneration after 150 years of life?

390. What is the annual rate of formation of methylglyoxal-derived AGE adducts (MG-H1) in serum proteins in clinically healthy 50-year-olds?

391. Which metabolic pathway, glycolysis-dependent methylglyoxal or the classical Amadori reaction, accounts for more than 60% of the vascular AGE load in people over 60 years of age?

392. How effective is pharmacological enhancement of endogenous deglycases DJ-1/Park7 and FN3K or the introduction of synthetic deglycases in reducing tissue AGE modification levels by 50% in rodents?

393. Can a combination strategy of low-glycemic diet + intermittent fasting + deglycase therapy maintain collagen elasticity at the level of 30-year-olds for three decades?

394. Which latent herpesviruses (EBV, CMV, HHV-6) show the greatest correlation with the acceleration of biological age by DNA methylation in immune cells?

395. Which viral proteins (e.g. EBNA2, IE1) directly interact with the enzymes DNMT1 and TET2, reconfiguring the host epigenome?

396. Could CRISPR/Cas9 excision of latent viral episomes from hematopoietic stem cells permanently eliminate virus-induced epigenetic noise without losing immune memory?

397.What is the reduction in biological age (in years as measured by the epigenetic clock) observed after complete eradication of latent herpesviruses from a primate model?

398.Which strains of gut bacteria (e.g., Clostridium sporogenes or Akkermansia muciniphila) produce the highest levels of indole-3-propionic acid in 100-year-old humans?

399.How does artificial elevation of intestinal indole-3-propionic acid affect serum IL-6 and C-reactive protein levels in 45- to 60-year-old volunteers?

400.Did cryopreserved autologous stool transplantation maintain stable, high levels of indole-3-propionic acid in the microbiome for 5 years?