Me: It would appear that the senescence of growth plates can not just be explained by one triggering step or mechanism like the idea that senescence of growth plates occur only from “growth plate senescence is caused by qualitative and quantitative depletion of stem-like cells in the resting zone” or that “senescence might occur because stem-like cells in the resting zone have a finite proliferative capacity, which is exhausted gradually”. I am sure that it is just one of the causes for growth plate eventual failure.
This new article that I have found seems to show the loss of DNA methylation is another main reason. I had found this article more than 2 months ago but at the time I did not understand what it was talking about so I had chosen not to read about it until now when I am more knowledgeable on the minute details on how the growth plates work. They have observed that the level of DNA methylation in resting zone chondrocytes decreased with age in vivo (within the lab animal). This drop seen in DNA methylation only occurs in the slow proliferation activity of chondrocytes in the resting zone of the animal, but nowhere else as the rate of DNA methylation stayed the same from the resting zone, to the proliferative layer, to the hypertrophic layer.
The conclusion reached is that the overall level of DNA methylation decreases during growth plate senescence. It agrees with the idea that (and I quote from the abstract
“hypothesis that the mechanism limiting replication of growth plate chondrocytes in vivo involves loss of DNA methylation and, thus, loss of DNA methylation might be a fundamental biological mechanism that limits longitudinal bone growth in mammals, thereby determining the overall adult size of the organism.”
Then the obvious question would be what then causes the loss of DNA methylation? plus the other more practical question, if we can reverse or inhibit the decrease in rate of DNA methylation, can we keep the mechanism for the replication of growth plate chondrocytes in the resting zone constant or even increase in numbers and capacity?
From PubMed website. source link HERE.
J Endocrinol. 2005 Jul;186(1):241-9.
Growth plate senescence is associated with loss of DNA methylation.
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. email@example.com
The overall body size of vertebrates is primarily determined by longitudinal bone growth at the growth plate. With age, the growth plate undergoes programmed senescence, causing longitudinal bone growth to slow and eventually cease. Indirect evidence suggests that growth plate senescence occurs because stem-like cells in the growth plate resting zone have a finite proliferative capacity that is gradually exhausted. Similar limits on replication have been observed when many types of animal cells are placed in cell culture, an effect known as the Hayflick phenomenon. However, we found that the number of population doublings of rabbit resting zone chondrocytes in culture did not depend on the age of the animal from which the cells were harvested, suggesting that the mechanisms limiting replicative capacity of growth plate chondrocytes in vivo are distinct from those in vitro. We also observed that the level of DNA methylation in resting zone chondrocytes decreased with age in vivo. This loss of methylation appeared to occur specifically with the slow proliferation of resting zone chondrocytes in vivo and was not observed with the rapid proliferation of proliferative zone chondrocytes in vivo (i.e. the level of DNA methylation did not change from the resting zone to the hypertrophic zone), with proliferation of chondrocytes in vitro, or with growth of the liver in vivo. Thus, the overall level of DNA methylation decreases during growth plate senescence. This finding is consistent with the hypothesis that the mechanism limiting replication of growth plate chondrocytes in vivo involves loss of DNA methylation and, thus, loss of DNA methylation might be a fundamental biological mechanism that limits longitudinal bone growth in mammals, thereby determining the overall adult size of the organism.
- PMID: 16002553 [PubMed – indexed for MEDLINE]