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I.R.F. / Aging news / Cloning / 05060701

Stem Cell Ageing
Posted on: June 7, 2005

The quantitative and qualitative effects of ageing on stem cells are not well understood, although it is believed that stem cells from a younger individual should have greater potential. Thus, many investigators suggest that fetal stem cells should have an advantage over adult stem cells in cell replacement therapies.

All stem cells invest heavily in self-protective mechanisms and can self renew, but whether or not they age over the lifetime of an individual is the subject of much debate. On the one hand, stem cells remain viable for the lifespan of a mammal, small numbers can repopulate the whole mammal and many life-ending diseases have mechanisms that do not involve stem cells. On the other hand, most stem cells, including those from fetal and adult tissues, are not immortal and show an increase in apoptotic mechanisms with age.
There is some evidence from murine models that the homing efficiency of older HSC is less than that of younger HSC, and adult stem cells are at a competitive disadvantage when transplanted with fetal cells. Older HSC have diminished self-renewal capacity, less developmental potency and give rise to decreased numbers of progeny when subjected to haemopoietic demands, and this decline in function is even more apparent when older stem cells undergo increased stress.
Similar qualitative effects of ageing are seen with MSC; older bone marrow stroma blunts haemopoietic responses after transplantation and increases post-transplant autoimmunity.

Most, if not all, stem cells produce telomerase, which lengthens telomeres, protects against genotoxic damage and correlates with cell immortality. The self-renewal and replicative potential of stem cells probably depends on telomerase to maintain stable telomeres, as most evidence indicates that telomere length is a biomarker of the replicative history of cells. Cells of the germline have very long telomeres, which do not shorten with ageing of the organism, and fetal stem cells could be expected to have an advantage over adult stem cells in this regard. Comparative studies of fetal liver and adult bone marrow HSC have confirmed that fetal liver HSC have higher telomerase activity and adult bone-marrow-derived HSC shorter telomeres, which again implies that the proliferative potential of HSC is limited and declines with age.

Source: Keelin O'Donoghue, Nicholas M. Fisk; Fetal stem cells; Best Practice & Research Clinical Obstetrics and Gynaecology; Vol. 18, No. 6, pp. 853-875, 2004; doi:10.1016/j.bpobgyn.2004.06.010
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