Basement membrane - adult stem cells

Health

How to have extreme longevity: 3. Keep adult stem cells young

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By Juman Hijab

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Original date: November 22, 2022  

Updated: February 10, 2023

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Table Of Contents
1
Aging cells  --> Aging stem cells --> Aging
1.1
 Aging stem cells as a result of an unhealthy stem cell niche
1.1.1
Dysfunctional niche --> aging stem cells
1.2
Aging stem cells  removed from an unhealthy niche rejuvenate
1.2.1
The age of the stem cell niche determines our age
1.3
Non-aging stem cells = longevity
1.4
Conclusion
1.5
References:
Aging cells

yomogi1. Diagrams of young skin and wrinkle. young skin is firm tight, its collagen framework is healthy. old skin sags as it loses its support structure. Shutterstock.com, ID: 1809479347.

Aging cells  --> Aging stem cells --> Aging


In the last article, I discussed the importance of having a prosperous stem cell population to prevent aging. This is well described in this review on the relationship between aging stem cells and an aging organism (1).


A healthy and flourishing system needs a  robust and dynamic cast of players. In this vein, animals that have strong regenerative capacity seem to have a a never-ending supply of stem cells. They also never age (2, 3, 4, 5).  


In addition, to maintain vigorous stem cells, it is crucial to have a young, energetic supporting cell niche (6, 7, 8, 9). When there are great supporting cells (a healthy niche), adult stem cells can avoid aging.


Interestingly, vertebrates (including humans) have developed well-defined stem cell niches to protect their stem cells (5, 10).

In this article - the third in the series - I will describe the importance of a vibrant environment to maintain the health of the stem cells.

Adult stem cells - aging cells

Designua. Stem cells. These inner cell mass from a blastocyst. These stem cells can become any tissue in the body. for example: neuron, chondrocyte, enterocytes, red blood cells, muscle, fat or epithelial cells. Shutterstock.com, ID: 595329806. 

 Aging stem cells as a result of an unhealthy stem cell niche

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As the fetus develops, adult stem cells are produced from the original handful of germ cells. Those adult stem cells are segregated into organ-specific niches. For example, intestinal adult stem cells are sequestered into intestinal niches (9). This helps in two ways: 
  • The adult stem cells are encouraged to stay quiescent until needed 
  • The adult stem cells can be easily activated as they get direct communication from the circulation as well as well as the nerves that support the niche

There are two groups of cells in the niche. Stem cells and supporting cells. The non-stem supporting cells in the niche support the stem cells, giving them enough nutrients to keep them healthy as well as protecting them from undue influence from the environment. This allows the niche the ability to rev the stem cells into activity, when there is a need for actively proliferating cells (for example, to replace lost cells or in cases of injury).

Dysfunctional niche --> aging stem cells

Unfortunately, on the flip side, when the the supporting cells are diseased, the stem cells suffer. Thus: 

  • An aging vascular plexus leads to dysfunctional neurogenesis. Neural stem cells that are present in key areas of the brain are deprived of key vascular-derived factors. This leads to a decrease in in both quantity and quality of the neural stem cells, contributing to an aging brain (11, 12, 13). 
  • Reduced brain repair in an aging brain is thought to directly contribution to memory loss (13).
  • Aging of the blood vessel cell niche (the vascular niche) is directly related to atherosclerosis as well as organ fibrosis (14, 15, 16).
  • Muscle mass loss during aging is related to an impairment in proliferative potential and activity of the muscle stem cells (satellite cells - 17) as well as aging of their stem cell niche (18, 19, 20).  
  • The immune system and the related cells in the bone marrow display age-related decline in function due to aging of the hematopoietic stem cell niche (21, 22).

Basically, an aging stem cell niche (both aging supporting cells and/or aging extracellular protein components - 21, 23) inhibit youthfulness of stem cells. This leads to reduced regenerative ability as well as aging stem cells. 

Stem cell niche

DALL·E 2-  picture of stem cell niche with capillaries and nerve axons, Feb 2023

Aging stem cells  removed from an unhealthy niche rejuvenate

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However, all is not lost. The fascinating  aspect of stem cell niches is that when you change the niche the stem cell can recover and rejuvenate!

  • Adding soluble factors released from young (embryonic) stem cells helped aging stem cells recover their regenerative ability (24)
  • When old mice - and human - cells are exposed to young circulatory blood, they demonstrate (21, 24, 25) improved regenerative capacity
  • Old muscle stem cells can be induced to become youthful with recalibration of their regenerative molecular pathways (25).
  • Central nervous system cells improved remyelination of nerves with the addition of young scavenger cells and youthful serum factors (26)
  • Scavenging senescent cells can help maintain the youthfulness of the stem cell niche. Animals - like salamanders - with incredible regenerative have the ability to do this automatically (27). This has been confirmed experimentally (28). 

The age of the stem cell niche determines our age

The common theme in many of those studies on rejuvenating stem cells is that stem cells - in general - do not lose their potency. They can recover when exposed to young serum and young cells, when old cells are removed from the milieu, or when they are encouraged to recalibrate. 

In summary, non-stem cells age. When they are placed close to stem cells, the latter age. This results in the aging of the organism. One is as old as the age of their stem cell niche. Conversely, rejuvenation is possible with restoration of the youthfulness of the niche surrounding the stem cells. 

Non-aging stem cells = longevity

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Interestingly, animals that have high regenerative capacity are incredibly ageless (see table in this article). Thus,  some turtles, salamanders, certain fish species (rougheye rockfish), some flatworms, quahog clams, and red sea urchins don't show signs of aging (4, 29, 30, 31). 


Long-lived animals with agelessness have various mechanisms to support longevity and high regenerative capacity. They make sure that their stem cells niche remains vibrant. I already mentioned the ability of salamanders to scavenge senescent cells away within regenerating tissues (27).


Other mechanisms for inducing longevity include higher serum levels of anti-aging proteins and hormones (31, 32, 33), activated pro-regenerative nuclear proteins (34, 35, 36, 37) and superb antioxidant systems ( 38, 39, 40).


The common denominator for agelessness and longevity is the ability to keep aging stem cells at bay. Unfortunately, for humans, the supporting niche cells undergo aging. This results in a messy environment for stem cells and they in turn start aging. 

Conclusion

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When you look at animals that have the ability to regenerate tissues and organs relatively easily after injury,  you can see that one of the distinguishing elements between them and animals that have lost this ability is that their supporting cell system is young and vibrant. 

Having strong stem cells - a lot of them - equals agelessness (5, 41). Complex animals (for example, vertebrates) don't have the luxury of a huge amount of stem cells (4). Not only that, their stem cells age over time. 

It is the supporting cells and a healthy niche that provide the secret of youth; you are only as old as the age of your stem cell niche.

References:

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Tags

aging, longevity, stem cell, young

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