Sharing a visualization developed for didactic and exploratory purposes, addressing the temporal dynamics of OSKM-mediated reprogramming in somatic cells.
#CellularReprogramming #YamanakaFactors #iPSC #Pluripotency #Epigenetics #Senescence #PartialReprogramming #SystemsBiology
Transient OSKM induction dynamics in aged fibroblasts: relative transcript abundance over a 6-day doxycycline pulse-chase.
#PartialReprogramming #YamanakaFactors #CellularRejuvenation #EpigeneticReprogramming #OSKM #AgingBiology #TranscriptionalDynamics #SystemsBiology
NSD1/NSD2, H3K36me2, and chromatin domain boundaries in aging
Publication trend (PubMed, 2006–2026): a low, irregular baseline of 0–2 papers/year through 2017, a sharp jump to 5 in 2018.
#NSD1 #NSD2 #H3K36me2 #epigeneticclock #Polycomb #DNMT3A #SotosSyndrome.
FANCM (PDB: 5V5X) — DEAD-box ATPase geometry (K1175/Mg²⁺) drives replication fork reversal at interstrand crosslinks, not classical duplex unwinding. Helicase–DNA interface: residues 1290–1297.
Fork reversal fidelity declines with age. FANCM's structural landscape is an underexplored target in replication stress and genomic aging.
#FANCM #FanconiAnemia #StructuralBiology #DNARepair #ReplicationStress #LongevityBiology #Biogerontology
WRN helicase (PDB: 2QZ2) — Walker A/B and Sensor 1 motifs coordinate ADP–Mg²⁺ in the post-hydrolysis state. C-terminal tail (L514) couples helicase and exonuclease activities.
WRN loss → Werner syndrome + simultaneous acceleration of telomere attrition, epigenetic dysregulation, and stem cell exhaustion. A structural window into multi-hallmark aging.
#WRN #WernerSyndrome #StructuralBiology #LongevityBiology #DNARepair #Biogerontology #AgingHallmarks
PARP1 (PDB: 4DQY) — catalytic core resolves NAD⁺ positioning (H133/E134/Mg²⁺) and substrate interface (326–332) as structurally separable sites. E134 as the ADP-ribose acceptor base.
Age-associated DNA damage → PARP1 hyperactivation → NAD⁺ depletion → SIRT1/3 inactivation → mitochondrial dysfunction. A structurally grounded feedforward loop in biological aging.
#PARP1 #NAD #StructuralBiology #LongevityBiology #Aging #DNARepair #Biogerontology #Sirtuins
LSD1 (KDM1A) demethylates H3K4me1/2 via FAD-dependent oxidation — removing active enhancer/promoter marks and licensing transcriptional repression.
In the CoREST complex, it couples demethylation to HDAC1/2-mediated deacetylation for compounded silencing.
LSD1 inhibition extends lifespan in model organisms. The local H₂O₂ byproduct at demethylation sites may be a redox signal — the full mechanistic picture isn't resolved yet.
EZH2 (PRC2) trimethylates H3K27 → PRC1 recruitment → chromatin compaction → transcriptional silencing.
Elegant at the mechanistic level. Consequential at the organismal level — elevated EZH2 activity shortens lifespan in model organisms, likely via progressive silencing of stress-response loci.
The SET domain may be one of the most underrated targets in aging biology.
#EZH2 #PRC2 #Epigenetics #AgingBiology #H3K27me3 #ChromatinRemodeling #Longevity
FOXO4-DRI = senescent cell eliminator
How it works:
→ FOXO4 normally binds p53 in senescent cells
→ FOXO4-DRI peptide displaces FOXO4
→ Free p53 triggers apoptosis
→ Senescent cells eliminated
Mouse studies: restored fur, kidney function, fitness
Selective killing = safe
mTORC1 = cellular growth/aging switch
ACTIVE (nutrients abundant):
→ Protein synthesis ↑
→ Autophagy ↓
→ Growth mode
INHIBITED (nutrient restriction):
→ Autophagy ↑
→ Stress resistance ↑
→ Lifespan extended (+13-26% in mice with rapamycin)
Trade-off: growth vs longevity
