This 2017 Baltimore/China rodent study found:
“MSPC [Mesenchymal stem/progenitor cell] senescence is epigenetically controlled by the polycomb histone methyltransferase enhancer of zeste homolog 2 (Ezh2) and its trimethylation of histone H3 on Lysine 27 (H3K27me3) mark. Ezh2 maintains the repression of key cell senescence inducer genes through H3K27me3.
Our work establishes the role of Ezh2-H3K27me3 as a key epigenetic regulator that controls the onset and progression of MSPC senescence during the transition of fast- to slow-growing phase of long bones.
The self-renewal and proliferative capacity of cells in primary spongiosa of fast-growing bones are maintained by a high level of Ezh2-H3K27me3, whereas loss of Ezh2-H3K27me3 during late puberty leads to cell senescence.”
One of the experiments led to this note in the Discussion section:
“An epidemiologic study demonstrated that 60% of the risk of osteoporosis can be explained by the bone mineral acquired by early adulthood.
Our finding that deletion of Ezh2 in nestin+ cells during early puberty increases the risk of osteoporosis in later adulthood suggests that premature cellular senescence in the primary spongiosa region during the prepubertal or early pubertal phase may also be a major cause of osteoporosis/bone loss in later life.”
The study was short of explanations in several areas. For example, causes for the “loss of Ezh2-H3K27me3 during late puberty” weren’t specified.
In another example, this statement referenced nestin-positive cells:
“Because these cells are likely no longer required in this particular region during adulthood, they stop proliferating and undergo senescence during late puberty.”
but what caused the cells to be “no longer required” wasn’t specified.
The “programmed” and “fate” words were used in the Abstract:
“Our data reveals a programmed cell fate change in postnatal skeleton..”
but not explained until the Discussion section:
“The senescence process is program[m]ed by a conserved mechanism because it restricts in a particular region of long bone and follows a specific time course.”
https://www.nature.com/articles/s41467-017-01509-0 “Programmed cell senescence in skeleton during late puberty”