5 replies to this topic

[Learner056]

Thank you to ya all with knowledge, I hope you can bear with me (I can be irritating) and help me in this journey (i.e. help answer questions I/noobs have, marking in red):  My goal here is to put anti-aging biology in some mental context, specially relating to: a) cell cycle, b) functional tissue cell vs stem cell, c) Telomeres.  Though please add more concepts if it can help this understanding. 

 

1.  Let us say, we begin our journey with One cell.  One cell divides into Two daughter cells.  This division process is called Cell Cycle. 

2.  Cell cycle repeats itself till Hayflick limit of the cell is reached?  Is it that when telomere length is left zero, Hayflick limit left = 0 also?

 

I think before we go further, some basic vocabulary also, if I get straightened: 

- Cell: has DNA (within Nucleus), Lysosomes/Ribosomes/ER/Mitochondria/Vacuoles etc (within Cytoplasm), Cell membrane

- DNA: important molecule of a living organism.

- Chromatin: is packing structure of DNA (it includes Histones - gene expression proteins)

- Chromosome: are made up of Chromatins (i.e. DNA protein complexes aka Nucleosomes)

- Chromatin changes aka Histone modifications: signify gene expression.

- Telomeres: Protective caps (i.e. Nucleo-protein complexes) at end of Chromosomes.  Significance: They mark time?, as they shorten with every cell division.

- Apoptosis: When telomeres run out (besides other reasons too)

- Senescent cell is: when cell has reached its hayflick limit (or got damaged), but did not apoptosed, and continues to hang around?.

 

3. The "Cell Cycle"

It seems to me that this cell cycle is for a typical functioning cell only.  How do stem cells come/fit into it?  Is there some mechanism that first cell tries to fulfill its hayflick potential, and only when it exhausts the cell cycles, that it utilizes a stem cell?

Cell cycle has a broad hoopla of vocabulary:  M phase, G1 phase, S phase, G2 phase (skipping all that)

 

Q1: When people say:  Cell differentiation (as in sometimes reported: 'cell did not fully differentiate'), do they mean stem cell differentiation? Since differentiation is concept related to stem cell, as stem cell differentiates into functioning cell A/B/C (where functioning cell can be organ specific, epithelial cell for tissue, cardiomyocyte for heart etc)

 

Q2: When people say: Cell proliferation.  This proliferation concept, I assume is applicable to both a functioning cell (as it will divide till hayflick limit achieved) as well stem cell? 

 

 

 

 

 

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Edited by Learner056, 02 September 2022 - 09:53 PM.

[Learner056]

Post#2:  I will proceed, regardless of whether the "havs" (those with knowledge) contribute to us (the "have nots").  The goal of this post is to a) elucidate the vocabulary of cell cycle, b) how Telomeres fit into this framework.  

 

So the Cell cycle can be viewed in 2 broader phases: Interphase and Mitosis (the Photo2 in Post#1).  Within these 2 buckets are:

M Phase (Mitosis phase): Chromosome segregates and cell division starts. 

• Nuclear Chromosome separates into 2 identical Nuclei
• It is divided into:
  • Prophase (chromatin condenses to form Chromosomes),
  • Metaphase (microtubules form, interacting with Chromosomes),
  • Anaphase (microtubules shorten, chromosomes separate),
  • Telophase (reformation of nucleur membrane).  Now nuclear division is complete.
• Cytokinesis: Now Cytoplasm starts to partition. 2 infant cells complete, each containing its nucleus.  

G1 Phase: Growth factors act on cells, allowing cells to double their mass (i.e. mass of proteins/organelles/genetic material). Checks occur.

S Phase: DNA Replication (i.e. synthesis) occurs

• Telomere length plays role here (or in G2-phase?).  Telomerase (which reverses Telomere shortening plays role here.  Stem cells have their own Telomerase)
• Cancer cells like Stem cells have high Telomerase.

G2 Phase: Cell completes dna replication.  Checks occur.  // I think these G or S phases have some deep secrets buried in them.  We will as one people help uncover them. 

 

[QuestforLife]

I am happy to contribute, though in a way it is useful to have someone without mental baggage of previously held knowledge asking basic (but instructive) questions.

 

Some of your questions may be answered in my thread, of which the latest contents list is here . The thread started as a log of my efforts to discover and develop ways to lengthen my telomeres, but has mainly become a research and discussion area for any interesting papers related to telomeres and how they influence aging. 

 

It has always been my belief that telomeres are central to aging, certainly human aging, though I also entertain other perspectives from time to time. 

 

A couple of random (unreferenced) points in response to your posts: Hayflick limit simply refers to the limit on the number of times (human) cells can divide. It was later found that in human cells that was related to telomere shortening; in mouse cells it is normally to do with senescence induced by reactive oxygen species. Hence the belief that telomeres are a hard limit on human lifespan (but not necessarily mice lifespan). Telomeres purely mark the number of mitotic divisions. Arrest is gradual and a complete cessation of division (even with continual growth stimulation) called senescence, it doesn't imply no telomeres are left, cells are stopped before this point (around 4-5 thousand bases remaining). If uncontrolled division is restarted due to faults in the normal checks, then telomeres are completely eroded away and then the chromosomes without telomeres are fused together by the cell's DNA repair machinery. This is a disaster as when the cell next divides and the chromosome halves are pulled apart by the spindles, they break in random places. So you end up with non-human cells (i.e. cancer cells). Epigenetic controls don't work on these cells as the genes are now in the wrong places. 

 

There is reckoned to be a hierarchy of dividing cells, going from, say white blood cells, up to intermediate progenitors that can become more than one cell type, up to stem cells in the bone marrow (its is more complicated than this, but you get the picture). This allows the stem cells to not divide much and keep themselves in reserve and there are various arguments about whether they have active telomerase to keep themselves 'young'. It appears that if human stem cells do have telomerase then it is very low levels. 'Differentiation' is the epigenetic process by which a stem cell daughter decides whether to remain as a stem cell or become a downstream cell needed by the body. The balance between renewal (stem cells dividing to make 2 stem cells) and differentiation (1 of each, or even 2 both differentiating cells) decides the fate of the tissue long term and is a complication on the telomere theory of aging. 

 

That's enough for now. I should add telomere science is mostly unmapped, there are many unanswered questions.  

Edited by QuestforLife, 05 September 2022 - 03:59 PM.

[Learner056]

QuestForLife, you added concepts, which is helpful - I appreciate that, though if we first create a 'conceptual architecture'.  The "Cell Cycle" (Post1, Photo2) is that conceptual architecture, but it does not talk the language of anti-aging.  I intend to revamp it, force it to speak longevity science.  So I am going to ask very simple, one question at a time only:

 

I am referring to the "Cell Cycle" here only: How do stem cells come/fit into it. Is there some approximate mechanism that first cell tries to fulfill its division potential (say it is 50x), and only when it exhausts this 50x potential, that it utilizes a stem cell?

 

 

Edited by Learner056, 05 September 2022 - 06:34 PM.

[QuestforLife]

QuestForLife, you added concepts, which is helpful (as we need to get to them ultimately), though if we first create a 'conceptual architecture'. The "Cell Cycle" (Post1, Photo2) is that conceptual architecture, but it does not talk the language of anti-aging. I intend to revamp it, force it to speak longevity science. So I am going to ask very simple, one question at a time only:

I am referring to the "Cell Cycle" here only: How do stem cells come/fit into it. Is there some approximate mechanism that first cell tries to fulfill its division potential (say it is 50x), and only when it exhausts this 50x potential, that it utilizes a stem cell?

In terms of the cell cycle a cell grows in size and then divides, in response to growth factors. It does this until it can no longer divide, either through telomere shortening, or more likely in the body through another kind of arrest such as coming into contact with other cells in an adult organ, for example. Then it just sits there doing its job unless other neighbouring cells die and then it divides (if able) to replace them.

In some organs where cells die often, like the skin or the gut lining there are physical layers with stem cells resident at the bottom and certain distress signals make them divide. This is most often asymmetric division, with the cell at the top graduating into a differentiated skin cell (say) and moving up into the upper skin levels and the cell at the bottom remaining a stem cell. In some circumstances the stem cells may divide the other way (i.e. spread out at the same level) if stem cells have died and need replacing through symmetric division.

The stem cells in the bone marrow are similar to how I described the skin, with one daughter cell remaining in the marrow and one leaving (into the blood stream) as a differentiated cell. What cell it becomes depends on the exact signalling and where it ends up,but most often it will end up as some kind of blood cell, which need constant replacement.

[Learner056]

Impressive - I am going through your work, QuestForLife.  Your manuscripts on Telomeres and mTOR, is a model work for scientists to follow - ties together various theories - sincerely and clearly.  This forum is lucky to have you.  I will take a break on this thread for some days and be back