Hallmarks of Aging: Stem Cell Exhaustion

Hallmarks of Aging: Stem Cell Exhaustion

A quick overview of what you’ll learn from this blog post:

  • What is stem cell exhaustion?
  • How it happens
  • The consequences of stem cell exhaustion

The Hallmarks of Aging describes stem cell exhaustion as the failure of stem cells and their ability to produce a supply of fresh somatic cells to organs and tissues. It is associated with aging phenomena such as frailty and the decline of the immune system, known as immunosenescence. It is also responsible for the failure of organs and tissues to regenerate and function.

The master cells that keep our organs and tissues alive

Ok, first things first, let’s explain what a stem cell is exactly. These are master cells from which all other cells in our body are created. These master cells are much more flexible when it comes to what they can do compared to the more specialized somatic cells which make up the bulk of our total cells.

This is because stem cells have a greater level of control over their gene expression pattern. We talked about gene expression and how changes to it can change cell behavior and drive the aging process in our article about epigenetic alterations.

Given the correct conditions in the body or a laboratory, stem cells will divide to make daughter cells. With appropriate chemical cues these daughter cells can be guided to becoming any type of cell in the body. Stem cells make up a small percentage of our total cells but keep our organs and tissues going with a supply of fresh healthy cells to replace those that die.

Stem cells not only supply tissues and organs with replacement cells, but also improve tissue function, regeneration, and health through beneficial signaling. This signaling has proven to be so useful for promoting tissue repair that some researchers are developing the chemicals they secrete as a form of therapy.

Because they provide a pool of replacement cells and their signaling keeps tissues and organs healthy, any loss of stem cell activity can have harmful consequences. This loss of activity accompanies the aging process and is known as stem cell exhaustion.

This phenomenon is linked to various conditions, including immunosuppression due to a decline of white blood cell production and frailty due to muscle loss and the weakening of bones.

How does stem exhaustion happen?

As we get older, the activity of our stem cells gradually slows down. This happens due to a number of factors.

  • Senescent cell accumulation
  • Inflammaging
  • Loss of stem cell populations

Senescent cell accumulation occurs as we age and is thought to be a reason we age. These problem cells secrete a cocktail of pro-inflammatory signals known as senescence-associated secretory phenotype (SASP). The SASP is immunosuppressive and inflammatory and reduces the activity of stem cells and its ability to regenerate tissue.

Inflammaging is a term used to describe systemic inflammation which typically rises with advancing age. It is fueled from a number of sources including, adverse changes to our gut bacteria (microbiome), cell debris, senescent cell accumulation and immunosenescence.

Loss of stem cell populations is also another reason why stem cell exhaustion happens. Just like somatic cells, stem cells can also be damaged and destroyed. Telomere attrition can cause stem cells to cease working and become senescent and even though they typically repair DNA damage better than regular cells, mutations can accrue to the point of causing cancer or cellular senescence. While losses to the stem cell pool are typically slower than normal cells, eventually it takes its toll.

What can we do about stem cell exhaustion?

It might all seem a bit complicated at first glance, but the good news is that researchers have some ideas about what might be done to combat this problem. There are even a few things you can do yourself too.

  • Clearing senescent cells using senolytic drugs to reduce SASP
  • Boosting NAD+ and metabolism to boost stem cell activity
  • Reducing inflammaging through good diet, lifestyle and exercise
  • Targeting the sources of inflammaging with drugs and therapies
  • Replacing lost stem cells with new patient-matched stem cells

The good news is that stem cell research is one of the most well funded areas of aging research and advances are coming at a steady pace. It is not unreasonable to believe that in the near-future researchers will be able to create any types of stem cells in the body and use them to replace age-related losses.