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You are here: Biology of Aging >

Dysfunction of Stem Cells Contributes to Aging

Stem cells are a type of cells primarily responsible for cell division in the body. When damaged cells in a tissue die, stem cells divide and differentiate to produce new cells to fill the gap. Thus stem cells are critical for the body's ability to heal and renew itself. It is well known that healing/regeneration capacity declines with age. At least in part, this decline appears to result from the dysfunction of stem cells. Indeed, it stand to reason that if stem cells are largely responsible for tissue renewal, then dysfunction of stem cells would impair healing/regeneration capacity and thus contribute to aging. Furthermore, the pro-aging role of stem cell dysfunction should presumably be more pronounced in the tissues with a lot of ongoing cell division, such as the skin or vascular & intestinal lining.

Indeed, there is growing scientific evidence that age-related stem cells dysfunction does indeed occur throughout the body and in the skin in particular. In a 2012 study, Dr Doles and colleagues (from the Center for Genomic Regulation [CRG], Barcelona, Spain) studied hair follicle stem cells in the skin of young and old mice and found a number of age-related impairments. As per Bill Keyes, group leader of the Mechanisms of Cancer and Aging lab at the CRG:

"We have discovered that major changes occur in these stem cells during aging, whereby stem cells exhibit impaired growth in older animals as compared to their more youthful counterparts. We also found that the aged stem cells are not able to tolerate stress as well as young stem cells, strongly supporting the idea that changes in stem cell function might actually drive the aging process."

The CRG researchers also found that while the stem cells increased in number during normal aging, they lost much of their functional capacity. They also noted there that such dysfunctional stem cells appeared to have higher potential to develop into cancer. CRG study also indicated that skin stem cell dysfunction correlated with high tissue levels of inflammatory cytokines (signaling molecules that promote inflammation). When "old" stem cell were placed in a different environment their function improved, indicating that stem cell dysfunction is at a least partially reversible.

A somewhat different type of stem cells dysfunction appears to occur in the muscle. In a 2012 study, Dr Joe Chakkalakal (from Massachusetts General Hospital) and colleagues found that age-related decline in the functional capacity of muscle stem cells appears to result from their overuse, i.e. they divide too often and their population gets depleted due to prolonged state of "overdrive". The researchers also found that a particular growth factor (a signaling molecule) call FGF-2 was responsible for overstimulating and eventually depleting muscle stem cell population. Inhibiting FGF-2 production largely prevented muscle stem cell dysfunction.

All in all, stem cell dysfunction appears to be prevalent throughout the body and contribute to many signs of aging as well as age-related diseases, including cancer, arterial sclerosis, diabetes and others. The primary factors causing/contributing to such dysfunction may vary somewhat from tissue to tissue and include inflammation, overstimulation and perhaps also oxidative stress, telomere shortening and others. The good news is that age-related stem cell dysfunction may be somewhat reversible. But just how reversible, in what tissues and by what means remains to be researched.

What are the practical implications of the evidence of age-related stem cell dysfunction? Can we make ourselves younger by somehow fixing or replacing dysfunctional stem cells? The short answer is: Not yet. The studies on reversing stem dysfunction have been performed in tissue culture and rodents using methods unsuitable for humans. This is only a tentative proof of principle. A practical way of "rejuvenating" old stem cells in humans remains to be developed, which is likely to take a long time.

What about simply injecting ourselves with lots of new fresh stem cells? Embryonic stem cell injection is already practiced, legally in some countries and not-so-legally in others. Unfortunately, this option may not do the trick either, even if it is legal in your country or you are willing to travel. The stem cells used in such injections typically come from discarded embryonic material. They are immunologically incompatible with your body and are going to be eventually rejected, i.e. attacked by you immune system as foreign just like a transplanted organ would be. Therefore, the injected stem cells are unlikely to provide your body with a permanent new stock of stem cells only a temporary boost at best.

The problem of rejection of the injected embryonic stem cells can be partly resolved by tissue type matching the same way it is done for organ transplants. If there were a tissue bank with a large number of diverse embryonic cells lines, it would be possible to find a reasonably close match and thus reduce the likelihood and severity of rejection. However, while such embryonic stem cell bank is technically feasible, it is unlikely not be created in the foreseeable future due to legal and ethical considerations. Finally, the stem cell rejection problem can be completely solved by using something called therapeutic cloning. But that technique is even further away from practical availability due to an even greater tangle of ethical, legal and technical concerns.

Where does this leave us? What can we do today to prevent and/or reduce the dysfunction of our stem cells? We know that inflammation is a key contributor to stem cell dysfunction, at least as far as the skin is concerned. Hence it is critical to keep inflammation to a minimum. The single most effective measure for reducing skin inflammation (and overall skin aging for that matter) is proper sun protection. Almost as important is to quit smoking (if you happen to smoke). Other inflammation fighting steps include better dental hygiene, exercise, weight loss (if overweight), and anti-inflammatory diet. (See our article on inflammation for more information.)


     


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