#1

Epigenetic alterations during ageing are manifested with altered gene expression linking it to lifespan regulation, genetic instability, and diseases. Diet and epigenetic modifiers exert a profound effect on the lifespan of an organism by modulating the epigenetic marks. However, our understanding of the multifactorial nature of the epigenetic process during ageing and the onset of disease conditions as well as its reversal by epidrugs, diet, or environmental factors is still mystifying. This review covers the key findings in epigenetics related to ageing and age-related diseases. Further, it holds a discussion about the epigenetic clocks and their implications in various age-related disease conditions including cancer. Although, epigenetics is a reversible process how fast the epigenetic alterations can revert to normal is an intriguing question. Therefore, this paper touches on the possibility of utilizing nutrition and MSCs secretome to accelerate the epigenetic reversal and emphasizes the identification of new therapeutic epigenetic modifiers to counter epigenetic alteration during ageing.

Full paper below:

sharma-shikha-epigenetic-modifiers-as-game-changers.pdf (910.9 KB)

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#2

Check out “Bazi Bushen mitigates epigenetic aging and extends healthspan in naturally aging mice,” Xinjing Mao et al., Biomedicine & Pharmacotherapy, Volume 160, April 2023, 114384.

An excerpt:
““We demonstrated a better efficacy of BZBS [Bazi Bushen] in liver methylation rejuvenation with larger sample size compared to the reported rapamycin treatment (Fig. 4C). Most importantly, the DNA methylation age reversal in response to BZBS treatment was then supported by decreased pathological changes and FI [Frailty Index] score, as well as enhanced memory ability and muscular performance. Our finding is the first reported example of TCM [Traditional Chinese Medicine] playing a role in the reversal of DNA methylation age and revealed the potential of BZBS in treating aging-related diseases by delaying aging process.”
Figure 4C shows that the mean methylation age of the aged mice was about 57 weeks. The BZH (BZBS high dose) group had a mean methylation age of about 40 weeks.

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Suggestions for ITP drugs to test
#3

Interesting and that is a quite good / quite ok impact factor journal. Also seems to work via SIRT3-FOXO1 pathway.

Perhaps should be a candidate for ITP?

From this it may also impact cellular senescence.

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Suggestions for ITP drugs to test
#4

Tune rais­es $175M to bring epi­ge­net­ic edit­ing to clin­ic

Paywalled article: https://endpts.com/tune-therapeutics-raises-175m-series-b-for-epigenetic-editing/

#5

There is a human study.

https://www.sciencedirect.com/science/article/abs/pii/S094471132400401X?via%3Dihub

The efficacy and safety of Bazi Bushen Capsule in treating premature aging: A randomized, double blind, multicenter, placebo-controlled clinical trial

Conclusions

BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging.

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#6

Here’s a preprint that might give some new insight on epigenetics:

Direct Intercellular Vesicle Exchange between Adjacent Cells

https://www.biorxiv.org/content/10.1101/2024.12.11.626728v1

I had some thoughts on this and then a few minutes ago I asked Gemini 2.5 Pro to give them a smell test. My thoughts were:

Neighboring cells maybe exchange genetic and epigenetic information, to keep their phenotypes synchronized (keeping them more similar). The fact that cells from different organs tend not to be directly connected to each other (apart from at certain small junction regions) limits this kind of information transfer between organs. This is a good thing since different organs have different epigenetic landscapes, with different sets of genes turned on or off to help them carry out their particular role in the body. That is, we don’t want skin behaving like the liver, say.

It seems this could also be a way to retain epigenetic information in the body as a whole. If all cells in a local patch of tissue should have the same epigenetic CpG site readouts (because they belong to the same organ), then variations could be smoothed-out over time through transfer of information between neighbors. Maybe a few cells get dysregulated, but then their neighbors transfer some of their information, which then pushes them back in line.

If all this is true, and if the effect is strong enough (i.e. doesn’t just minimally change the epigenome of cells), then perhaps compounds or supplements that increase cell-cell adhesion might magnify the effect. If adhesion goes up, then the separation between cells in a tissue should go down, which should make it easier for information to be transmitted by extracellular vesicles between neighboring cells.

Gemini 2.5 Pro’s analysis of my thoughts:

The study’s findings not only support your hypotheses but also provide a framework for further investigation into the role of this novel communication pathway in development, health, and disease.

Ok, so maybe supplements and drugs that increase or maintain cell-cell adhesion are worth looking into
 (Following a Google search I see that vitamin D, vitamin A, omega-3, Astaxanthin, etc. might help with this; but there may be better candidates.)

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