STEM CELL EXHAUSTION – The Ultimate Culprit of Aging
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.
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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:
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
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
The effects of exhaustion
As we age, some of our adult stem cells repair and regenerate cells that have experienced wear and tear, injury or disease. They are not involved in normal tissue function, but remain quiescent – a state in which they do not divide, yet retain the ability to proliferate highly specialized cells specific to the organ and tissues where they reside. They are activated when the need arises. The unique ability of adult stem cells to maintain quiescence is crucial for life-long tissue homeostasis and regenerative capacity.
The activation process of quiescent stem cells is very complex and requires precise reorganization to transition into a proliferative state, and it, unfortunately, declines over time. The consequences of stem cell exhaustion manifest in different ways, depending on the type of stem cell affected.
· Hematopoietic (blood-forming) stem cell (HSC) exhaustion results in anemia and myelodysplastic syndromes, a group of blood disorders where stem cells do not mature into healthy blood cells.
· Mesenchymal stem cells (MSCs) are found in bone marrow. They are important for making and repairing skeletal tissues, such as cartilage, bone and the fat found in bone marrow. When they become exhausted, osteoporosis can set in, as well as decreased fracture repair.
· Myosatellite cells, or muscle stem cell exhaustion shows up as hindered repair of muscle fibers.
· Intestinal epithelial stem cells (IESCs) are one of the most rapidly renewing cell populations in the body. When these become exhausted, one might accurately guess that intestinal function will be negatively impacted.
Help is on the horizon
It is estimated that the number of adults older than 65 will reach upwards of 88.5 million by 2050. With this staggering number in the forefront, it is more important than ever to find therapeutic interventions to improve stem cell function.
As mentioned above, induced pluripotent stem cells are being avidly researched in order to more thoroughly understand the potential they could have on healing. While it is an absolutely promising and likely option to look forward to, it has not been perfected yet.
This brings us to the point, as it has in each blog of this hallmarks of aging series, where we look at what we can do in the meantime. The most promising and recent research illustrates the connection between a fasting-mimicking diet and the body’s ability to regenerate stem cells.
USC researchers found that a fasting-mimicking diet reduced intestinal inflammation and increased intestinal stem cells, in part by promoting the expansion of beneficial gut microbiota. The research team observed that the fasting component allowed the intestines to heal, but that the specific, calorie-restricted diet allowed the microbes in the gut to flourish, which was crucial to the stem cells rebuilding and regenerating.
Valter Longo, the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences says, “This study for the first time combines two worlds of research. . .The first is about what you should eat every day, and many studies point to a diet rich in vegetables, nuts and olive oil. The second is fasting and its effects on inflammation, regeneration and aging.”
What else can I do?
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