Running Out of Gas? The Ultimate Culprit of Aging – Part 1

Written by Anil Bajnath, MD
Posted April 13, 2021

Dear Longevity Insider,

Stem cells have exceptional abilities to self-renew and recreate functional tissues. When this regenerative potential begins to decline in our bodies, many researchers believe it is the defining moment when we begin to see age-related conditions manifest.

We have written about seven of the nine Hallmarks of Aging. The first four are considered primary since they are believed to be actual causes of aging and have a definitive negative effect on DNA. They are what first initiate cellular damage, which then leads to accumulation and progressive loss of function. They are:

  • Genomic instability
  • Telomere attrition
  • Epigenetic alterations
  • Loss of proteostasis

The next three are called antagonistic, as they ultimately respond to the damage caused by the primary hallmarks. However, they are initially designed to have protective factors. It is only when bodily conditions become chronic and/or aggravated that they contribute to cellular damage.

They are:

  • Deregulated nutrient-sensing
  • Mitochondrial dysfunction
  • Cellular senescence

The last two hallmarks are thought to be integrative because they “directly affect tissue homeostasis and function.” These come into play once the accumulated damage caused by the primary and antagonistic hallmarks can no longer be stabilized. Once this happens, the functional decline is inevitable.

They are:

  • Stem cell exhaustion
  • Altered cellular communication (more on this next week!)

This week, we will cover stem cell exhaustion. In one way or another, each primary and antagonistic hallmark of aging culminates in the diminished self-renewing capacity of stem cells, thus the reason it is identified as one of the two integrative hallmarks.

The marvel of stem cells

Your body comprises more than 200 cell types. Your liver cells are replaced every 300-500 days; your skin cells, every couple weeks; and your taste buds every 10 days or so. Your body continually manufactures new blood cells to replace old ones, and about 1 percent of the body’s blood cells must be replaced every day. White blood cells have the shortest life span, sometimes surviving just a few hours to a few days, while red blood cells can last up to 120 days or so.

Stem cells are the foundation for every organ and tissue in your body. While there are many types of stem cells, three are best known: embryonic, adult, and induced pluripotent.

Embryonic stem cells begin forming within five days after fertilization. They exist only in the earliest stages of development and are considered pluripotent, or undifferentiated, as they have the ability to give rise to every cell type in the fully formed body.

Adult stem cells, also known as somatic or tissue-specific stem cells, are multipotent, meaning they differentiate to yield the specialized cell types of the tissue or organ in which they reside, and may have defining morphological features and patterns of gene expression reflective of that tissue. These adult stem cells are responsible for repairing or replacing damaged tissue as we age or experience injury.

For therapeutic and research purposes, scientists are also able to generate induced pluripotent stem cells by re-introducing the signals that normally tell stem cells to stay as stem cells in the early embryo. These switch off any genes that tell the cell to be specialized, and switch on genes that tell the cell to be a stem cell. Cells go through several stages while differentiating and become more specialized with each step. Signals secreted by other cells, physical contact with surrounding cells, and other molecules present in the body all contribute to the differentiation process.



Figure 1: An illustration showing different types of stem cell in the body.
Image credit: Genome Research Limited

On Thursday, we'll dive more into some of our adult stem cells repair and regenerate cells.

To your longevity,

Anil Bajnath MD
CEO/Founder, Institute for Human Optimization
Chief Medical Officer, Longevity Insider HQ