Linear chromosomes are capped by structures known as telomeres.
In mammals, telomeres contain tandem repeats of TTAGGG double-stranded DNA.
Telomere length varies among mammals.
For example, in humans, telomeres are typically 10–15 kb whereas, in some strains of mice telomeres are approximately 100 kb in length.
Telomerase, a nucleoprotein reverse transcriptase, elongates telomeres.
However, most normal somatic human cells do not express telomerase activity and are unable to maintain telomere length with ongoing cell divisions.
As a result, telomere length in replicating somatic cells tends to decrease with age in vivo and with time in culture at a rate of approximately 100 base pairs per cell division.
The telomere hypothesis of cellular senescence proposes that normal somatic cells become senescent and thus stop replicating when progressive telomere shortening during cumulative cell division produces a threshold telomere length.
However, recent evidence suggests that telomere shortening is not the only counting mechanism responsible for replicative senescence in vitro.
Furthermore, the relationship between senescence in vitro and aging in vivo and the relationship between telomere shortening and aging in vivo remain unclear.
In mammals, growth plate chondrocyte replication slows with age and eventually ceases, causing linear growth of the organism to slow over time and finally stop.
Recent studies suggest that proliferative growth plate chondrocytes are derived from stem-like cells in the resting zone and that replication slows because these stem-like cells have a finite replicative capacity that is gradually exhausted.
It has been therefore hypothesized that the replicative capacity of growth plate chondrocytes is limited by telomere shortening; as the stem-like cells in the resting zone slowly replicate, their telomeres may gradually shorten, resulting in cellular senescence.
Previous studies suggest that telomere length declines in human articular cartilage during adulthood, but no previous studies have assessed telomere length in the growth plates of young mammals.
To test this hypothesis scientists harvested resting zone chondrocytes from mice (Mus casteneus) of different ages.
They then used Southern blot analysis to determine whether the telomere length of these chondrocytes decreases with age and with longitudinal bone growth.
They have found that TRF length did not diminish appreciably with age in mouse resting zone chondrocytes.
This lack of telomere shortening was observed from postnatal week 1, when longitudinal bone growth is rapid, until postnatal week 8, when longitudinal bone growth has slowed markedly.
A minimal decrease in TRF length may be present at 56 weeks, but at this time, skeletal growth has essentially halted.
As a control, they have measured TRF lengths of the resting zone chondrocytes in two different mouse strains, M. casteneus and M. musculus, at the same age.
They have found that TRF length was greater in M. musculus than in M. casteneus .
Several other lines of evidence also suggest that telomere shortening is not the mechanism responsible for growth plate senescence.
First, telomerase-deficient mice do not show abnormalities in skeletal growth.
In these mice, telomere length decreases with succeeding generations, and abnormalities begin to occur in some highly proliferative types of cells.
However, skeletal growth remains largely unaffected.
Second, among different mammalian species, telomere length does not correlate with skeletal size.
For example, some strains of mice have substantially longer telomeres than do humans, despite the fact that skeletal growth lasts longer and results in greater bone length in humans than in mice.
Third, in different strains of mice, telomere length varies greatly without a corresponding difference in skeletal size or duration of the growth period.
The lack of measurable telomere shortening in mouse resting zone chondrocytes observed in the current study could reflect the slow proliferation rate in this portion of the growth plate.
Alternatively, the lack of shortening could be caused by the presence of telomerase in this tissue.
In mice, unlike humans, telomerase activity is found in normal, somatic tissues in vivo.
In conclusion, telomere length does not decrease measurably in mouse resting zone chondrocytes during skeletal growth.
This finding indicates that replicative senescence of growth plate chondrocytes in mice is not due to telomere erosion in resting zone cells.