Longevity Questions

Perpetual Prompt ♾️, [09.05.2025 00:37]
1231. What is the minimum level of p53 activity (in % of basal expression in young cells) required to completely block tumor transformation of human fibroblasts in vitro without inducing apoptosis?
1232. What number of single nucleotide substitutions (≤ n) in the TP53 regulatory element is sufficient to stably double p53 expression in mouse liver cells in vivo?
1233. What is the maximum threshold for off-target mutation rate (CRISPR-Cas9, < ppm) acceptable when editing the p53 signaling cascade to maintain the risk of carcinogenesis at the control level?
1234. What is the optimal NAD+/NADH ratio in cardiomyocyte mitochondria to reduce the level of γH2AX foci by 20% in 72 h?
1235. What is the minimum expression level of folate cycle genes (FOLR1/FOLH1) required to double the base excision repair (BER) rate in neurons?
1236. At what methylation level (−Δβ ≥ 0.15) does the cg11625005 site in the TERT promoter switch from "on" to "off" in lung epithelial cells?
1237. How many 48-hour cycles of partial reprogramming (OCT4, SOX2, KLF4) are required to reduce the epigenetic age of human fibroblasts by 5 years according to the Horvath scale?
1238. What is the minimum number of senescent cells (< % of tissue) that must remain after senolytic therapy to maintain full regeneration of "super-ager" mice?
1239. How many petabytes are needed to store a 24-hour transcriptome profile of all major human organs (≥ 30 tissues) with an accuracy of 0.1 RPKM?
1240. What level of telomere length/loss (≤ bp per year) correlates with a probability of survival to age 200 > 1% in the Gompertz–Makeham population model?
1241. What oxygen tension (mmHg) in the hypoxic “embryo mimicry” minimizes the mutational background of mitochondrial DNA in cardiomyocytes?
1242. What threshold of SIRT6 sirtuin activity (U/mg protein) is needed to halve the frequency of double DNA breaks in skin cells after UV irradiation with 100 mJ/cm²?
1243. What is the K_D (nM) of a small molecule p53 activator that selectively binds to the "AD2" conformation without inhibiting p63/p73?
1244. How many copies of mitochondria per cell must be replaced by mTEXT to restore oxphos to levels of 30-year-old donors in cells from 70-year-olds?
1245. What is the minimum CD4+/CD8+ ratio (> x) after thymic IL-7 "revaccine" to ensure a 25% reduction in mortality from infections in 90-year-olds?
1246. At what liver β-glucuronidase level (U/L) does the plasma half-life of resveratrol increase threefold?
1247. What is the cytokine index range (C-reactive protein < mg/L) needed to predict a 10-year delay in cardiac phenotypic aging using cardiac MRI?
1248. What is the minimum heteroplasmy level (< %) of the m.3243A>G mutation for suppression of POLG errors to ensure full restoration of ATP synthesis in neurons?
1249. What is the optimal final acetyl-CoA/coenzyme A ratio in hepatocyte cytosol to suppress chronic NLRP3 inflammasome in the liver?
1250. What is the M2/M1 macrophage index (≥ x) in visceral fat needed to reduce systemic IL-6 to a threshold level of 1 pg/mL?
1251. How many contact hours (h/day) of social cognitive stimulation are required to reduce the rate of hippocampal shrinkage by 0.3% per year in people aged 80+?
1252. What level of the Klotho β-form gene copy (ΔCt control – sample ≤ x) ensures a 10% decrease in plasma phosphate without disrupting mineral metabolism?
1253. What is the minimum threshold of L-serine (μM) in the cerebrospinal fluid required to reduce glutamate-dependent excitotoxicity in the cerebral cortex of old mice by 15%?
1254. What level of YAP factor (TPM) expression in the endothelium ensures 7% regression of fibrous plaques in 6 months?
1255. At what distance between ALU repeats (≤ kb) in the 3'-UTR of the SIRT3 gene does the frequency of alternative splicing increase, reducing its expression by half?
1256. How many steps (≤ n) of PE-3b editing are needed to completely replace the senile G-quadruplex structure in the LMNB1 promoter with the youthful variant?

Perpetual Prompt ♾️, [09.05.2025 00:37]
1257. What is the minimum value of the metabolic flexibility index (RQ range) needed to reduce the accumulation of AGE cross-links in dermal collagen by 30% per year?
1258. What single volume of blood perfusion (ml/kg) with the addition of carboxy-Hb is needed to reduce tissue hypoxia in the heart of old rabbits by 25%?
1259. At what decrease in PKC-β activity (%) in adipocytes does TNF-α secretion decrease to 0.5 pg/ml, which correlates with an increase in insulin sensitivity by 20%?
1260. What mass charge (Gy/day) of low-dose proton irradiation optimally activates DAMP signals without increasing the incidence of HPRT mutations > 10⁻⁷?