Longevity Questions

Perpetual Prompt ♾️, [08.05.2025 20:43]
541. What is the minimum degree of LINE-1 suppression in human somatic cells required to reduce systemic SASP inflammation by ≥50% without compromising immune tumor control? 
542. Is it possible to selectively “neutralize” all active copies of LINE-1 masters in blood cells using CRISPR base editing without creating off-target mutations, and will this result in a ≥30% increase in healthy lifespan in mouse models?
543. What expression profile of domesticated retroviral genes (Arc, Syncytin-1/2, PEG10) in the CNS correlates with human cognitive "age" and can it be used as a predictor of the biological rate of brain aging? 
544. Is partial pharmacological blockade of the ORF2 LINE-1 endonuclease permissible in the germline without disrupting fertility and normal embryogenesis in primates? 
545. Can training of the immune system with an mRNA vaccine encoding repeat-specific L1/Alu peptides enhance senescent cell clearance and increase the median lifespan of SASP reporter mice? 546. How does plasma metabolomics change after chroniotropic lamivudine treatment in healthy elderly individuals and are these changes associated with improvement of the Horvath-PACE epigenetic clock? 
547. Can deep learning (Graph Neural Networks) predict which of the individual L1 insertions in the human genome are “hot” and contribute to the blood interferon background? 
548. How much does HERV-K-env repression reduce neuroinflammation in a model of τ protein accumulation-induced neurodegeneration and how does this affect long-term memory? 
549. Does combination therapy “RT-inhibitor + classical senolytic (Navitoclax)” synergistically increase the maximum lifespan (ω-pool) in mice compared to monotherapy?
550. What percentage of the placental syncytiotrophoblast transcriptome that is reactivated in aging tissues can be safely silenced without compromising epithelial regeneration? 
551. Can silencing of Arc capsid expression in the hippocampus of mature mice slow down interneuronal amyloid transfer and delay the onset of cognitive decline? 
552. Which methylated CpG islands in the promoters of active L1s are the best pharmaco-targets for a SAM analog that can selectively enhance DNMT methylation without global hypermethylation? 
553. How robust is the anti-L1/Alu piRNA cluster profile to epigenetic drift in centenarians (≥100 years), and can it be artificially rejuvenated in vivo?
554. Does downregulation of SETMAR transposase expression in hematopoietic stem cells reduce the incidence of age-associated chromosomal aberrations? 
555. What level of circulating L1-cpDNA (circular partial DNA) in the blood is an early marker of "latent" systemic inflammation 5 years before clinical multimorbidity? 
556. Are there tissue-specific domesticated TEs that regulate liver regeneration, and can they be enhanced with CRISPR-a to accelerate recovery after resection? 
557. Does upregulation of the domesticated PGBD5 gene in neuronal precursors affect cortical plasticity and the rate of recovery after ischemic stroke?
558. Can syncytin-suppressing peptides be used to prevent pathogenic cell fusion in age-associated muscle atrophy without impairing wound healing? 
559. What evolutionarily conserved motifs in ORF1p are required for RNP granule formation and are they suitable for allosteric inhibition? 
560. What is the minimum dose of a systemic STING antagonist that can ablate L1-induced IFN-I without critically weakening antitumor immunity in aged mice? 
561. How much will downregulation of Helitron-like fragments in the human genome affect the three-dimensional architecture of TAD domains and the expression of longevity-related genes?
562. Can transient upregulation of the KRAB-ZFP superfamily ZNF with CRISPR-on reduce repeat expression more effectively than global methylation and be reversible?

Perpetual Prompt ♾️, [08.05.2025 20:43]
563. Which interactions between Arc-VLP and brain extracellular fluid microRNAs are critical for maintaining subventricular zone neurogenesis? 
564. Which Alu polymorphisms in xenobiotic metabolism genes are associated with increased resistance to mitochondrial toxicity of nucleoside RT inhibitors?
565. Is it possible to create a “smart” senolytic targeting cells with high L1-ORF2p expression using LYTAC-tagged protein therapy? 
566. Is the frequency of ectopic recombination of Alu pairs reduced after increasing topoisomerase III β expression and how does this affect the rate of telomere shortening? 
567. Which domesticated thymus-expressed TE peptides are needed to expand the T cell repertoire in individuals over 70 years of age? 
568. Is it possible to insert “protective mutations” (stop codons) into hot gene clusters of L1 masters using prime-editing without inducing a p53 response?
569. How does the systemic metabolic network (Flux Balance Analysis) correct L1-RT suppression in the liver: are NAD⁺/NADH fluxes and fatty oxidation signatures altered?
570. What safety parameters must be achieved for the combination therapy “partial epigen rollback + RT inhibitor” to move into the clinic for long-term use in middle-aged people?