Epigenetic Alterations - Hallmark of Aging 3

May 27, 2024

Epigenetic Alterations, Hallmark of Aging 3

Can you define the "epigenome"? It's not your DNA. It's not the genes tucked into your mitochondria. It's not even DNA. It's the markers on the outside surface of your chromosomes that curiously pass on some of their information to subsequent generations.

For example, two famous famines, in northern Sweden in early 1900 and in Holland during World War II, the offspring of those who suffered through those starvation times can be shown to still have metabolic abnormalities into the third generation. Another example, emotions that pass on in families reflecting generational trauma or even just cultural trends have some of their roots in epigenetic measures. Is that what drives the persistence of racism and its painful recurrent generational trauma?

Another example is likely the means by which all animals pass on their advice to their offspring. Fear of predators and safety of groups appears to be ingrown. Yet deer, living in safe places (our suburbs) become so accommodated to humans they are brazen in their nibbling on our flowers. The elk of Estes Park in Colorado are famous for their virtual occupation of the town. They have no fear. Town is safe. Their DNA has not changed. What passed on their behavior? Likely epigenetic changes.

Your epigenome is the markers on the outside of your DNA that instructs your body when to hold 'em and when to fold 'em. When to activate DNA and when to shut it down. There are some 20,000,000 of them on your chromosomes in complex web. You can attach a one-carbon signal (methyl group) or a two-carbon signal (ethyl group) to DNA or to the histone proteins. Each has separate signals.

Then there are the Sirtuin proteins tasked with caring for your DNA. Humans have 7 of them. Single-celled primitive life forms only have one sirtuin. The sirtuins are the groomers and repair specialists of your epigenetic system. They run on the NAD energy system instead of the ATP system. It's much less efficient and much more primitive, suggesting that sirtuins have been central to cells duplicating themselves since time immemorial. NAD declines with aging.

Hence, David Sinclair in his awesome book, Lifespan, argues that you need to take metformin, the diabetes drug at a 25% of effect (500-800 mg a day) to stimulate the production of more sirtuins, and NAD (otherwise known as niacin or Vitamin B3) in order to power them. This is all in the service of caring for your epigenome.

The frontier of cancer care now is all about measuring the detectable alterations in your epigenome that lead to cancer risk (marked reduction in markers). There are even companies offering cancer screening with high rates of specificity for some cancers. It's very complex because the 20 million markers aren't written in plain English, but pattern recognition is beginning to take hold.

Epigenetic modification mechanisms are still being discovered. There are all sorts of messenger RNA including circular mRNA and micro RNA particles that aren't coding for proteins that have epigenetic actions. If you want a really deep rabbit hole, type in retrotransposons and aging. (DNA segments that can get up and move their place in chromosomes and wreak havoc.). They play a role in cellular senescence, a cardinal sign of epigenetic exhaustion.

www.What will Work for me. I have used epigenetic markers to measure my biological age compared to my calendar age. I have used epigenetic markers in my clients to look for cancers, with satisfying responses. I'm taking metformin and NAD to care for my epigenome. I'm stymied about the complexity of it all but I do know that simply allowing my body to get into ketosis helps most of this. Prolonged starvation is such a drag, but a bit of induced starvation (skipping breakfast) or manufactured starvation (energetic exercise) likely accomplish the same thing, without the death part.

References: Cell, Oxford Handbook of Emotional Dysregulation, Overkalix Study-Wikipedia, American Jr Biolog Anthropology, Lifespan by Sinclair,

Pop Quiz

1. What is your epigenome?                     Answer: The markers on your chromosomes that indicate when to activate and when to silence genes.

2. Do you actually pass those genes on to your kids?                   Answer: Yes, to some degree. How, we don't quite know yet.

3. What are those markers?                       Answer: simple one and two carbon compounds, methyl groups and ethyl groups.

4. What are the proteins tasked with caring for your epigenome?                   Answer: The sirtuin family, stimulate by metformin and powered by NAD.

5. Can you name one dramatic effect of metformin and NAD?                        Answer: No fair, this answer takes reading Sinclair's whole book. But here it is. Recently menopausal women may get their period back when starting metformin and NAD. Some may not think of that as a major leap forward.