Fight Aging!

Most of your tissues are in a constant state of flux, the cells within a mix of those destroying themselves after dividing too many times, those dividing to create new cells to make up the numbers, and a smaller flow of fresh cells with many divisions remaining that are created by a small population of stem cells. Some tissues turn over their cell populations very rapidly, such as blood or the lining of the gut. Others consist largely of cells that will last as long as you live, such as much of the central nervous system. In all these cases, however, an embedded population of stem cells supports continued maintenance and function. If stripped of stem cells you would crumble into premature death in perhaps a decade or so.

That said, aging is effectively a process of being stripped of stem cells in addition to all of its other detrimental consequences. The maintenance of tissues diminishes degree by degree with the years until organs and systems fail, eventually fatally. Modern research suggests that, for those tissues where there is good data, the stem cells are still largely present, however. They have simply relinquished their jobs, lapsing into lasting quiescence or senescence in response to rising levels of damage. This set of affairs most likely evolved as a cancer suppression mechanism, our natural life span a balance between risk of death by tissue failure versus risk of death by over-active damaged cells spawning a cancer.

Experiments in moving stem cells between young and old tissue environments suggest that most types of old stem cells examined to date are quite ready to get back to work - and even do their jobs effectively despite their age - if only the signals present in their environment instructed them to do so. It is expected that if one could wave a wand in old humans and restore stem cells in all tissues to youthful activity, the result would be a lot of cancer in addition to improved tissue maintenance, however. Still, temporarily altering specific signals to boost stem cell activity has great potential as a therapy for the near future, with raised risk of cancer compensated for by an increasing effectiveness in cancer detection and treatment. First generation stem cell transplants are in effect a way of making native cells do more than they would otherwise have done by adjusting the balance of signals in the affected tissues. In years ahead more sophisticated methods will be used to achieve better and more controlled results in the same vein.

Ultimately the goal of rejuvenation by repair of cellular and molecular damage will hopefully automatically lead to restoration of stem cell activities. If the damage goes away, so too should the signaling environment that is a response to that damage.

Here is a readable review paper on stem cells present in adult tissues and their relationship to aging. There is a lot of detail packed in there, so take a look at the whole thing:

Adult Stem Cells and Diseases of Aging

Adult stem cells serve to replenish and direct repair at sites of tissue injury throughout the body, and exhaustion of dysfunction of an adult stem cell population in vivo with age results in degenerative disease. Several finely tuned and contextually regulated pathways coordinate the activities of tissue-resident adult stem cell pools over time in response to a host of cellular stressors in an effort to maintain the balance between growth-promoting function and oncogenic resistance. Manipulation of one or more of these pathways has the potential to prevent or reverse the impact of advancing age on adult stem cell function, but is fraught with the difficulty of tipping the balance toward metabolic derangement, or more likely toward cancer formation. Harvest and manipulation of adult stem cells ex vivo for use in regenerative medicine is a piecemeal approach to addressing systemic age-related chronic illnesses, but for now may prove to be a safer approach. In this regard, it is noteworthy that the clinical safety of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) has been well documented, not in the least on the basis of decades of successful clinical outcomes of heterologous bone marrow transplantation.

Given the growing evidence that many diseases of aging may reflect adult stem cell exhaustion, it is not surprising there is great interest in restoring adult stem cell function to ameliorate these conditions and regenerate aged tissues. Adoptive transfer of fetal MSCs into adult mice has been shown to extend median lifespan of the animals. Adult stem cell mobilization and transplant are two obvious strategies that have achieved moderate success for certain types of injury and disease in humans, and many types of adult stem cells have been utilized for this purpose. MSC cellular therapy has proven to be safe for a number of vascular disorders and is an attractive option for patients who are poor surgical candidates.

Despite these successes, the problem remains that adult stem cells from elderly donors, the very people who most frequently require enhanced peripheral stem cell function for tissue repair, undergo changes in their functional capacity as a result of aging. This decline in functional capacity, therefore therapeutic utility, has been combatted using some surprisingly simple interventions: Conditioning with hypoxia prior to transplant, for example, has been extensively documented as effective for reducing reactive oxygen species production by adult stem cells and improving their therapeutic efficacy in many in vivo ischemia and other disease models. This has proven sufficient to counteract the impaired oxidative stress resistance of MSCs from elderly donors.

Further development of therapeutic approaches to maintain these cells in vivo requires that the mechanistic basis of their age-related degeneration or renewal be understood. This is an area continually being informed by studies of early-onset aging syndromes and of families exhibiting extreme longevity. Transcriptional reprogramming, which effectively wipes away all signs of age from most cell types, is also yielding valuable insights into what makes a cell young or old. Rejuvenating stem cells to stave off aging safely will require highly innovative approaches, but the results of this research will have far-reaching implications for regenerative medicine.