Partial Reprogramming and Rejuvenation

[FTM1000]

Can someone explain me some studies I saw about partial reprogramming and rejuvenation?.

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679279/

Multi-omic rejuvenation of human cells by maturation phase transient reprogramming - https://www.biorxiv.org/content/10.1101/2021.01.15.426786v1.full

Is there anything in the first research that suggest that the rejuvenation that you get from partial reprogramming need constant maintenance(constant treatment) in order to endure? or that the results are permanent and will change only as a result of normal aging?. What the second research say about it?. And what kinds of aging related damage does partial reprogramming can reverse according to the second research?.

I don't have a degree or any significant knowledge in biology so I hope someone will explain me those studies in more simple words.

 

[jim mcnamara]

I'm going to simplify - a lot. Your body is made of cells. Each one (in general) has DNA, uses it, and tries to repair problems with it.

Background:
The epigenome is a way to think about how environment and ageing affect the chemical switches that the DNA slowly acquires over time. The study of the DNA switches is called epigenetics. At the very beginning of life, changes are needed to let cells change from the embryo into a living person. This is called cell differentiation - and epigenetics is part of the programming changes needed to get a single cell to divide and change into lots of different functioning cell types. All in the right location.

Humans start out as a single cell. Adults have a huge number of cells, trillions. So cells change function and divide to become organs and bone, and brain etc. Epigenetics reprograms DNA to new uses as we mature into an adult.

As we age other epigenetic changes occur. Not all good.

A made up example: DNA of identical twins shows very small epigenetic differences at age 1. At age 75 there are many many epigentic differences that have built up over time. The environment and habits like smoking influence which switches are turned off or back on. Or diddled with. Eventually some part of a cell's DNA no longer works as planned. The cell then may die or misbehave.

This leads to ageing affects and disease processes like organ failures or cancers.

Stem cells from an older adult do not have epigenetic baggage and damage. They can be used to replace messed up cells. Or regrow into new organs or tissues in some organs. In theory.

The papers are discussing the use of stem cells to correct ageing effects. One approach: Reprogram the problem DNA by replacing old broken cells in organs with new stem cells. There are lots of problems to overcome.

You need to realize that DNA in cells "lives" in the nucleus, and can also mutate with cell divisions. Plus. A different set of DNA lives in the many mitochondria inside the same cell. So it not simple at all.

Does that help at all?

 

[FTM1000]

I'm going to simplify - a lot. Your body is made of cells. Each one (in general) has DNA, uses it, and tries to repair problems with it.

Background:
The epigenome is a way to think about how environment and ageing affect the chemical switches that the DNA slowly acquires over time. The study of the DNA switches is called epigenetics. At the very beginning of life, changes are needed to let cells change from the embryo into a living person. This is called cell differentiation - and epigenetics is part of the programming changes needed to get a single cell to divide and change into lots of different functioning cell types. All in the right location.

Humans start out as a single cell. Adults have a huge number of cells, trillions. So cells change function and divide to become organs and bone, and brain etc. Epigenetics reprograms DNA to new uses as we mature into an adult.

As we age other epigenetic changes occur. Not all good.

A made up example: DNA of identical twins shows very small epigenetic differences at age 1. At age 75 there are many many epigentic differences that have built up over time. The environment and habits like smoking influence which switches are turned off or back on. Or diddled with. Eventually some part of a cell's DNA no longer works as planned. The cell then may die or misbehave.

This leads to ageing affects and disease processes like organ failures or cancers.

Stem cells from an older adult do not have epigenetic baggage and damage. They can be used to replace messed up cells. Or regrow into new organs or tissues in some organs. In theory.

The papers are discussing the use of stem cells to correct ageing effects. One approach: Reprogram the problem DNA by replacing old broken cells in organs with new stem cells. There are lots of problems to overcome.

You need to realize that DNA in cells "lives" in the nucleus, and can also mutate with cell divisions. Plus. A different set of DNA lives in the many mitochondria inside the same cell. So it not simple at all.

Does that help at all?

It doesn't answer my question, but it is good to have a general explanation about the subject in general.
Are all my questions hard to answer?, I know that the question about what types of damage partial-reprogramming can reverse might be difficult but what about my first question about if those changes endure?. From what I understand, there is no reason for those changes made by partial-reprogramming to disappear once you completely stop with the partial reprogramming treatment, am I right?.

 

[Rive]

there is no reason for those changes made by partial-reprogramming to disappear once you completely stop with the partial reprogramming treatment, am I right?.

Actually, you are asking something like 'what would happen after the experiment'?

That would belong to the next paper/experiment.

Spoiler: Spoiler

An actual (mathematician's ) answer is likely something like 'all specimen was cremated'.

 

[FTM1000]

Actually, you are asking something like 'what would happen after the experiment'?

That would belong to the next paper/experiment.

Spoiler: Spoiler

An actual (mathematician's ) answer is likely something like 'all specimen was cremated'.

But can't we know what is more likely to happen based on current knowledge?.

 

[FTM1000]

Just found an answer about the endurance of the results from partial reprogramming:
https://link.springer.com/article/10.1007/s11357-021-00358-6
in "Table 1 Studies of partial epigenetic reprogramming" there is a table with experiment on partial reprogramming and the duration of their effects and in most cases the effects only lasted for several days.

Now I have a different question, is there anything in this article that suggest a possible reason for why those changes doesn't last? or a way to make those changes permanent?. The article does say that partial reprogramming hold a great promise for treating aging, and it also suggest the following:
"A suggestion is an approach similar to the one shown by Ocampo et al. [28], but with the inclusion of a treatment that enhances genome stability during the absence of pluripotency factor expression. Short expression of pluripotency factors followed by administration of metformin, rapamycin, or even resveratrol would slightly flip the epigenetic landscape followed by the formation of deeper grooves. Perhaps this procedure would both improve lifespan extension and hinder the development of cancer and senescent cells.".
does this have anything to do with making the results of the partial reprogramming more permanent?.