Replicative capacity of tissues from normal human populations

The maximum replicative potential for mitotic cells varies between different cell types. Some cell types, such as endothelial cells, may have a maximum replicative capacity around 30 cPD (cumulative population doublings) while other cell types such as embryonic fibroblasts may have a maximum replicative capacity of 100 cPD. For example, one early study looked at the replicative capacities of several different tissue types (skeletal muscle, bone marrow spicules and mesial of the midupper arm) taken from donors of the same age (Martin et al, 1970). It was found that the replicative capacity of these tissues, despite being taken from the same individual, displayed variation in their replicative capacity. Cultures derived from skin fibroblasts achieved the greatest number of population doublings, bone marrow spicules the least and skeletal muscle giving intermediate results. There are a number of explanations for these observations. The first is that all cells do have the same replicative capacity, but the replicative history (rate of cell turnover) of each tissue at the time of extraction is so different that such variation is observed. Some tissues may have undergone a higher rate of cellular turnover than others, thereby exhausting its replicative capacity earlier. The second is that the replicative history of each tissue is similar, but it is the length of the telomeres between tissues that differs. Some tissues may senesce sooner than others because they started out with shorter telomeres. It is unlikely that these explanations alone are correct. A combination of the two is the most likely cause for such variation in replicative capacity. Tissues differ in both their replicative history and replicative capacities.

The results also show that the replicative capacity of the same tissues between individuals of the same age also differs. This difference may again be due to the same differences which effect proliferative variability between different tissues of the same individual. For example, one individual may have a shorter replicative capacity in a particular tissue than another of the same age due to increases in cell turnover, maybe in response to disease or injury, or maybe differences in initial telomere lengths. Cultured human embryonic fibroblasts were found to senesce at 50±10 cPD (Hayflick and Moorehead, 1961). This meant that some cultures were senescent only after 40 cPD while others at 60 cPD. These differences in replicative lifespan may be a consequence of the stochastic mechanism which triggers a cell to senesce. Therefore, the difference in replicative capacities of the same tissues between individuals of the same age may also be due to the stochastic events which govern a cell becoming senescent. Thus, the replicative capacity of a tissue measures biological age and not chronological age. Unfortunately there have been few studies looking at the replicative capacity of different tissues from the same individuals. This would have given a better insight into the relationship between chronological and biological age.

1 comment:

Oki said...

In fact the actual replicative potential of a given cell is even more variable than a given population. It has been shown that the same Wi38 fibroblasts that Dr. Hayflick studied actually senesce anywhere b/w 10 and 120 PDs.
On the other hand, in my experience a given passage of cells is much more consistent than +/- 10 PDs. I think the variation comes from differences in how individual researchers handle them, rather than huge stochastic variation in populations themselves. Thus if I freeze several vials of primary fibroblasts down at PD 25 then thaw one out and it senesces at PD 50, I can actually expect the next vial to do the same +/- 1 PD. If *you* give me a frozen vial of the same cell line and tell me it is at PD 25, however, it could come out anywhere b/w 40 and 60.

The main focus of ageing research is to prevent/combat age-related disease and disability, allowing everyone to live healthier lives for longer.