RNA Pol II itself works on the DNA and produces mRNA. However, there is complex around RNA Pol II that includes the Histone Acetyl Transferase (HAT). The process of enzymatic acetylation does not occur separately to transcription.
The HAT is not part of RNA Pol II, but is part of the complex.
HDAC inhibitors really bring me back. I remember it being really interesting to read, there was this guy called musicman on reddit who was all about it, he might’ve been manic at the time he was writing about it, still very good.
From the post: "Examples of natural compounds that have HDAC inhibiting properties include resveratrol, EGCG and Curcumin. Though he warns that smokers shouldn’t take curcumin.
I don’t know how much he knows, but curcumin has many potential benefits.
Reducing gene transcription IN GENERAL is a “good thing” (that’s what CR does, it’s what rapamycin does, that’s what SIRT6 does). It’s only a bad thing when you reduce gene transcription of GOOD GENES like Nrf2 or lysosome TFs
Excess undegraded/damaged protein (=> lipofuscin/aggregome) is easier to play into the “hallmarks of aging” (b/c it’s damage) than “insufficient production of essential proteins” [b/c we still don’t know *what* those proteins are) [this can still play into loss of homeostasis, but this is more subtle, and I dare say, this occurs at a much slower rate than actual damage from the aggregome]
Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence
Cellular senescence is a potent tumor suppressor mechanism but also contributes to aging and aging-related diseases. Senescence is characterized by a stable cell cycle arrest and a complex proinflammatory secretome, termed the senescence-associated secretory phenotype (SASP). We recently discovered that cytoplasmic chromatin fragments (CCFs), extruded from the nucleus of senescent cells, trigger the SASP through activation of the innate immunity cytosolic DNA sensing cGAS–STING pathway. However, the upstream signaling events that instigate CCF formation remain unknown. Here, we show that dysfunctional mitochondria, linked to down-regulation of nuclear-encoded mitochondrial oxidative phosphorylation genes, trigger a ROS–JNK retrograde signaling pathway that drives CCF formation and hence the SASP. JNK links to 53BP1, a nuclear protein that negatively regulates DNA double-strand break (DSB) end resection and CCF formation. Importantly, we show that low-dose HDAC inhibitors restore expression of most nuclear-encoded mitochondrial oxidative phosphorylation genes, improve mitochondrial function, and suppress CCFs and the SASP in senescent cells. In mouse models, HDAC inhibitors also suppress oxidative stress, CCF, inflammation, and tissue damage caused by senescence-inducing irradiation and/or acetaminophen-induced mitochondria dysfunction. Overall, our findings outline an extended mitochondria-to-nucleus retrograde signaling pathway that initiates formation of CCF during senescence and is a potential target for drug-based interventions to inhibit the proaging SASP.