Show #2678 condensed dialogue
Epigenetics, Longevity and Health-span
with guest, Erin Sharoni

Carl Lanore:
In this show, with a backdrop of a lot of good research, we’re going to talk about epigenetics, and how we can take actionable steps so that we can age better.

Erin sent me a stack of studies which she included as sources for her thesis. I'm fascinated by so many of them. I'd like to start with the very first one, transgenerational, epigenetic inheritance.

We talked about an interesting case yesterday, an old study where they took male rodents. and allowed them to smell cherries. They shocked them every time they smelled cherries to the point where, anytime they smelled cherries, they’d flinch like they were going to get shocked. Their offspring inherited that awareness trans-generationally. There are a lot of myths about trans-generational epigenetics. How much should we pay attention to? How much is meaningful?

Erin Sharoni: [00:06:53]
There’s a study that was published out of Harvard at the end of 2020, where they were able to restore vision in mice by basically resetting the epigenetic program. That study is absolutely fascinating, but it also illustrates the fact that there are still many things we don't understand mechanistically. For instance, if there is a “backup copy” of the epigenome, (which is what their theory is predicated upon), where is it stored and how do the enzymes involved with reprogramming know what to reprogram?

These answers, we do not have. In Waddington’s landscape, the idea is that all cells in the body arise from the same place, any cell can become any other cell type.  All the cells in your body contain the same DNA. But the liver cell is expressing certain genes so that it's a liver cell and the skin cell is expressing certain genes so that it's a skin cell and so on. That’s due to epigenetic chemical marks. That's really important when you talk about the germline and development. Epigenetics is high level regulation of cellular identity. Those regulatory mechanisms break down over time. Sometimes due to aging but other times, that breakdown is driving the aging process.

Carl Lanore:
Is there evidence that there is an epigenome that is completely tabula rasa in its original state, somewhere in our body that is being used when the blueprint is needed?

Erin Sharoni: [00:10:01]
We don't know. That's the ultimate question. At the Sinclair lab at Harvard they were able to reverse the epigenetic information damage in optic nerve cells in a mouse, they crushed them essentially. Eyes are very susceptible to aging and very hard to work with. They sought to approach the problem and reverse the damage by reprogramming or resetting the epigenome. How can you go back on this timeline far enough to be healthy and clean, but not so far that you're back to square one. They ended up applying three of the Yamanaka factors instead of four. They eliminated C-Myc which is associated with cancerous cell proliferation and they were able to restore some amount of vision in these mice and in doing so they showed a youthful epigenomic state. So the question remains: How does that happen? Is there the backup copy? If so, where is it? Even more interesting is you need Tet enzymes in order to instigate this process. The cells that did not have Tet enzymes didn't work in the reprogramming.  What's the role of Tet enzymes and how do they know to reset the program to a certain point.

Carl Lanore:
There are things we can do to improve our sleep like eat better quality food, drink, better quality water, think about our environment and our exposure to RF from our routers and our iPhones and all these things play a role. Supplementation with certain important nutrients play a big role too.

Carl Lanore: [00:32:09]
Let’s talk about sirtuins. 

Erin Sharoni:
To isolate the role of one specific ingredient or one specific enzyme or protein isn't effective as there are entourage effects. Most things are not occurring in isolation, the body is a complex organism. There are certain sirtuins in humans that play a very important role in homeostasis and affect a lot of functions including things that are integral to aging. They function in the presence of NAD.

Juvicell contains heavily researched ingredients that have shown efficacy in various areas related to longevity, such as mediating inflammation, DNA damage repair, potentially senescence, which is something we're looking at in a study now. From a cellular perspective at least, these ingredients have been studied individually and been shown to illicit certain effects that we believe in combination are likely to be even more effective.

Glucosomine, for example, appears to be a good mediator of inflammation controlling cytokine release. We live in a society with tons of chronic inflammation which is a source of accelerated aging. How that chronic inflammation is induced and sustained may vary from person to person but if you're taking something that's helping to mediate inflammation in a way that's healthy and, and helpful to the organism then you may see these specific benefits.

Carl Lanore: [00:40:23]
There's a study that you sent that discusses the hallmarks of aging. What are the hallmarks of aging?

Erin Sharoni: [00:43:58]
There was a paper back in 2013, that defines these nine main hallmarks of aging. The paper also bucketed them with three categories. The nine hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication.

There are three buckets: primary hallmarks, antagonistic hallmarks, and integrative hallmarks. In the primary hallmarks bucket are, genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis . In the antagonistic hallmarks bucket are mitochondrial dysfunction, deregulated nutrient sensing, and cellular senescence.  In the integrative hallmarks bucket, are stem cell exhaustion and altered intercellular communication.

Carl Lanore: [00:45:39]
What about metabolic debris accumulation? For example, those of us who eat a lot of red meat. What about the concept that our body accumulates so much debris as we go through life that it fouls up cell function, DNA replication etc.?

Erin Sharoni: [00:46:47]
Yes, autophagy is very important. When your cellular debris clearance system becomes compromised, whether we're talking about autophagy or the glymphatic system in the brain. It's essentially like the lymphatic system, but it's occurring in your brain. This fairly new idea suggests that it's cleaning out at night, by pumping the cerebral spinal fluid through your brain, it's cleaning out some of those metabolic byproducts that are naturally occurring during the course of your day, including tau and beta amyloid plaques associated with neurodegenerative disease. If you think about aging overall, with regard to these different hallmarks and in these different buckets, what you see is a picture of dysregulation, of a loss of information and direction.

It's this breakdown of all of these important systems over time. We can look at them in isolation to better understand mechanisms and how things fit together. But when you think about something wholisticly, like an organism aging, there's many different inputs in the body, different mechanisms and when you affect one, you usually affect another one.

Carl Lanore: [00:50:04]
Juvicell is a wonderful product. I use it I believe in it and it's something that I will use for a long, long time.

Juvicell:  shrnetwork.biz/livebetter use the code SHR20, you'll save 20%.

STUDIES:

Transgenerational Epigenetic Inheritance: Myths and Mechanisms
The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight
Epigenetic changes during aging and their reprogramming potential
Reprogramming to recover youthful epigenetic information and restore vision
Erosion of the Epigenetic Landscape and Loss of Cellular Identity as a Cause of Aging in Mammals
DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging
The Hallmarks of Aging
SIRT1 Redistribution on Chromatin Promotes Genomic Stability but Alters Gene Expression during Aging
Reprogramming the Epigenome With Vitamin C
Aging and DNA methylation
The aging epigenome