Senolytics ⇒ How Genome Sequencing and Senolytics Can Help Us Live Healthier, Longer

[biohacker112]

Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.

What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely.

These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse.

Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification, to localized inflammatory conditions such as osteoarthritis, to diminished lung function.

https://singularityhub.com/2019/02/01/h ... er-longer/

[CeeJayBee]

Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.

What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely.

These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse.

Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification, to localized inflammatory conditions such as osteoarthritis, to diminished lung function.

https://singularityhub.com/2019/02/01/h ... er-longer/

OK, so what is the proposed genome sequencing solution?

Now I have to read the article!!

- later -

Ok, so it looks like once you have identified the errant cells, it may be possible to edit them.

From the same article...

CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally-occurring biological system discovered in 1987 called CRISPR/Cas9.

Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.

Here’s how it works:

The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays.
The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions.
If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.
Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome.

A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.

[canadahealthy]

So... this is somewhat outside the realm of the work that NMN, NAD+ or Resveratrol, since they protect and repair DNA simply by increasing their levels, and or by restoring the levels of youth.

Gene editing is a completely different set of theories or theoretical processes that may not be in our immediate future, while these sirtuin modulators are here now... correct?

Is Alive By Nature pursuing gene editing?

[jocko6889]

These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse.

One of the molecules is called CD38, which neutralizes NAD+ and is a primary reason why levels of NAD+ decrease as we age.

[Youvion]

I think the general link between NAD+ increase through NMN precursors is that with higher NAD+ levels at the cellular level, the incidence of senescent cells will be less because the cells are functionally "younger" in their operation since NAD+ is such a fundamental chemical for many cell functions. Younger cells don't malfunction at the same rate as older cells, thus a reduced rate of these zombie senescent cells.

Depending on CRISPR to find and edit senescent cells is a pipe dream. The problem is how to identify senescent cells from normal cells. Still an open area of research I understand.

[jocko6889]

I think the general link between NAD+ increase through NMN precursors is that with higher NAD+ levels at the cellular level, the incidence of senescent cells will be less because the cells are functionally "younger" in their operation since NAD+ is such a fundamental chemical for many cell functions. Younger cells don't malfunction at the same rate as older cells, thus a reduced rate of these zombie senescent cells.

Depending on CRISPR to find and edit senescent cells is a pipe dream. The problem is how to identify senescent cells from normal cells. Still an open area of research I understand.

I agree that cells behave "younger" with increased NAD+ levels but I don't think it affects the number of cells that become senescent. Rather, NAD+ affects the ability of the immune system to mop up senescent cells as it did at a younger age. With or without increased NAD+, cells still run up against the Hayflick limit.

"The Hayflick Limit is a concept that helps to explain the mechanisms behind cellular aging. The concept states that a normal human cell can only replicate and divide forty to sixty times before it cannot divide anymore, and will break down by programmed cell death or apoptosis."

The problem is that with less energetic immune cells caused by lower levels of NAD+, these cells that have reached their Hayflick limit are allowed to hang around, secreting toxins that turn surrounding cells senescent as well. Increasing NAD+ levels is therefore an indirect senolytic as it revitalizes the immune cells to perform as they did at a younger age, mopping up senescent cells.

[Drdavid]

This is a great explanation