Longevity Questions

Ser ♾️, [08.05.2025 10:14]
278. What are the primary molecular "triggers" of epigenomic drift after puberty and can they be reset?
279. What combinations of CRISPR edits in somatic cells fundamentally reduce the rate of aging without increasing the risk of cancer?
280. Where is the safe limit of somatic mutation rate for a 200-year-old organism?
281. How does complete chromatin engineering (e.g., nucleosome repackaging) affect long-term expression of longevity genes?
282. What reversible epimutations are critical for age-related loss of cellular identity?
283. Is it possible to stabilize the "epigenetic clock" at the level of the adolescent profile and what are the risks?
284. Which rare human variations (CETP, SERPINE1, LRP5, etc.) contribute most to extreme longevity and how can they be copied polygenically?
285. How can synthetic chromosomes and non-canonical codons protect the genome from the accumulation of mobile elements?
286. How can the efficiency of the NER and BER DNA repair pathways be fully restored after 120 years?
287. What is the limit of proteasome activity during chronic senescence suppression?
288. Is it possible to create a universal “proteostatic drive” that automatically removes all protein aggregates in vivo?
289. Which post-translational modifications of proteins are irreparable with age, and how can they be specifically removed?
290. Which new chaperones can prevent misfolded conformers specific to aging cells?
291. How to stop or reverse clonal mitochondrial mutations in high-energy tissues?
292. Is it possible to “hot-swap” mitochondria in postmitotic brain cells without an immune response trigger?
293. How to reprogram the cellular energy sensor (AMPK/mTOR) so that it remains in a “youthful” mode for 200 years?
294. What is the minimum level of ROS required for signaling, and where is the line between benefit and harm when they are chronically suppressed?
295. How far can human basal metabolism be artificially reduced without reducing cognitive and physical function?
296. What signals transform the acute SASP response into chronic “inflamm-aging,” and can they be selectively blocked?
297. What frequency of “senolytic cleansing” of tissues minimizes harm and does not impair regeneration?
298. Is it possible to restart senescent cells into a normal division cycle without carcinogenesis?
299. How to reprogram the innate immune system so that it does not lose phagocytic activity after 150 years?
300. What key cytokine nodes determine systemic aging, and how to “silence” them without immunosuppression?

Ser ♾️, [08.05.2025 10:14]
301. ​​Is there an “immune limit” to longevity, and what needs to be changed to shift it?
302. How to maintain the pool of hematopoietic stem cells in a young epigenetic state at 200 years?
303. What factors of skeletal muscle niches are critically depleted with age and how to replenish them?
304. How to control the nuclear-cytoplasmic exchange in cardiomyocytes to allow their division after 100 years?
305. Is it possible to create “spare” multipotent niches in the body that are activated on demand?
306. How to ensure synchronous regeneration of the nerve, blood vessels, and extracellular matrix during organ rejuvenation?
307. Which neuroendocrine nodes of the hypothalamus trigger systemic aging, and how to “reflash” their signaling cascades?
308. How to preserve cognitive plasticity and memory with multiple epigenetic “rollback” of brain cells?
309. What is the optimal hormonal “signature” (GH/IGF-1, insulin, sex hormones) for an organism 150+ years old?
310. How do neurons maintain the axonal transport system without degradation for more than a century, and how to enhance this process?
311. Which collagen covalent crosslinks are irreversible and how can they be enzymatically broken in vivo?
312. How can mechanotransduction be regulated so that “stiff” old tissues return to elastic properties without fibrosis?
313. Where is the “mechanical limit” of the aorta and heart valves with a 200-year service life?
314. What key microbial metabolites determine aging via the gut → brain → endocrine axis?
315. How can a synergistic microbiome be stabilized in the face of decades of antibiotic, probiotic, and dietary therapy?
316. How does chrono-nutrigenomics (meal timing + genotype) change the pace of biological aging?
317. Is it possible to create completely artificial blood (erythro- and thrombo-substitutes) with a resource of 200 years?
318. How to integrate senolytics and immunotherapy so as not to increase the latent oncorisk?
319. Where is the critical threshold of clonal hematopoiesis (CHIP), compatible with 200 years of life?
320. Is it possible to safely use periodic "global" teleomeric lengthening without oncogenic side effects?
321. What universal cellular markers distinguish "normal" superlong cell cycle from cancer proliferation?
322. What resolution and frequency should single-cell multiomics have to scan the entire body monthly?
323. How Will new biosensors allow continuous monitoring of key signaling metabolites in blood and interstitium in vivo?
324. How should AI models for biological age prediction explain their decisions for clinical use?
325. What is the minimum set of nanorobots needed to autonomously repair cellular damage without immune rejection?
326. How can we ensure fair and ethical access to radical life extension technologies?
327. How can we regulate the boundary between clinical testing and commercial use of interventions that can extend life to 200 years without inhibiting innovation?