Stem cell theory of aging

The stem cell theory of aging is a new theory which was recently formulated by several scientists and which postulates that the aging process is the result of the inability of various types of stem cells to continue to replenish the tissues of an organism with functional differentiated cells capable of maintaining that tissue (or organ) original function. Damage and error accumulation in genetic material is always a problem for systems regardless of the age. The number of stem cells in young people is very much higher than older people and this cause a better and more efficient replacement mechanism in the young contrary to the old. In other words aging is not a matter of the increase of damage, but a matter of failure to replace it due to decreased number of stem cells. They decrease in number and tend to lose the ability to differentiate into progenies or lymphoid lineages and myeloid lineages.

Maintaining the dynamic balance of stem cell pools requires several conditions. Balancing proliferation and quiescence along with homing (See niche) and self-renewal of hematopoietic stem cells are favoring elements of stem cell pool maintenance while differentiation, mobilization and senescence are detrimental elements. These detrimental effects will eventually cause apoptosis.

There are also several challenges when it comes to therapeutic use of stem cells and their ability to replenish organs and tissues. First, different cells may have different life spans even though they are originated from the same stem cells. (See T-cells and erythrocytes) meaning that aging can occur differently in cells that have longer lifespans as oppose to the ones with shorter lifespans.Also, continual effort to replace the somatic cells may cause exhaustion of stem cells.[1]

Research

Some of the proponents of this theory have been Norman E. Sharpless, Ronald A. DePinho, Huber Warner, Alessandro Testori and others. Dr Warner came to this conclusion after analyzing human case of Hutchinson's Gilford Syndrome and mouse models of accelerated aging.

Stem cells divide more than non stem cells so the tendency of accumulating damage is greater. Although they have protective mechanisms,they still age and lose function. In fact Matthew R. Wallenfang, Renuka Nayak and Stephen DiNardo showed this in their study. According to their findings, it is possible to track male GSCs labeled with lacZ gene in Drosophila model by inducing recombination with heat shock and observe the decrease in GSC number with aging. In order to mark GSCs with lacZ gene, flip recombinase (Flp)-mediated recombination is used to combine a ubiquitously active tubulin promoter followed by an FRT (flip recombinase target) site with a promotorless lacZ ORF (open reading frame) preceded by an FRT site. Heat shock is used to induce Flp recombinase marker gene expression is activated in dividing cells due to recombination. Consequently, all clone of cells derived from GSC are marked with a functional lacZ gene. By tracking the marked cells, they were able to show that GSCs do age.[2]

Another study in a mouse model shows that stem cells do age and their aging can lead to heart failure. Findings of the study indicate that diabetes leads to premature myocyte senescence and death and together they result in the development of cardiomyopathy due to decreased muscle mass.[3]

Evidence Against the Stem Cell Theory of Aging

Diseases such as Alzheimer's disease, end-stage renal failure or heart disease are caused by different mechanisms that are not related with stem cells. Also, when it comes to some diseases related to hematopoietic system such as aplastic anemia and complete bone marrow failure, they are not especially age-dependent. Moreover, a dog study published by Zaucha J.M, Yu C. and Mathioudakis G., et al. also shows evidence against the stem cell theory. Experimental comparison of the engraftment properties of young and old marrow in a mammal model, the dog, failed to show any decrement in stem cell function with age.[4]

Other Theories of Aging

The ageing process can be explained with different theories. These are evolutionary theories, molecular theories, system theories and cellular theories. The evolutionary theory of ageing was first proposed in late 1940s and can be explained briefly by the accumulation of mutations (evolution of ageing), disposable soma and antagonistic pleiotropy hypothesis. The molecular theory of ageing includes phenomena such as gene regulation (gene expression), codon restriction, error catastrophe, somatic mutation (accumulation of genetic material damage) and dysdifferentiation (DNA damage theory of aging). The system theories include the immunologic approach to ageing, rate-of-living and the alterations in neuroendocrinal control mechanisms. (See homeostasis). Cellular theory of ageing can be categorized as telomere theory, free radical theory (Free-radical theory of aging) and apoptosis. Stem cell theory of aging is also a sub-category of cellular theories.

Footnotes

  1. ↑ Smith J., A., Daniel R. Stem Cells and Aging: A Chicken-Or-Egg Issue?. Aging and Disease. 2012 Jun, Vol.3, Number 3; 260-268.
  2. ↑ Wallenfang M. R., Nayak R. & DiNardo S. Aging Cell (2006) 5, pp297-304. doi:10.1111/j.1474-9726.2006.0221.x
  3. ↑ Rota M., LeCapitaine N., Hosoda T., Boni A., De Angelis A., Padin-Iruegas M., E., Esposito G., Vitale S., Urbanek K., Casarsa C., Giorgio M., Luscher T., F., Pelicci P., G., Anversa P., Leri A., Kajstura J. Diabetes Promotes Cardiac Stem Cell Aging and Heart Failure, Which Are Prevented by Deletion of the p66shc Gene. Circ res. 2006;99:42-52. doi:10.1161/01.RES.0000231289.63468.08
  4. ↑ Liang Y., Zant G., V. 2008. Aging stem cells, latexin, and longevity. Experimental Cell Research 314 doi:10.1016/j.yescr.2008.01.032

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