Cellular senescence — the process of aging at the cellular level — may play a role in the development of primary progressive multiple sclerosis (PPMS) by limiting the ability of myelin-producing cells (oligodendrocytes) to renew and mature.
The study with that finding, “Cellular senescence in progenitor cells contributes to diminished remyelination potential in progressive multiple sclerosis,” was published in the journal PNAS.
As MS is characterized by the loss of myelin on neurons — demyelination — therapeutic strategies to reverse this process (and promote remyelination) make sense intuitively. However, such strategies are inherently limited by the body’s capacity to produce new myelin. This, in turn, is limited by whether oligodendrocyte precursors cells (OPCs) can differentiate into mature, myelin-producing oligodendrocytes.
The team behind this study previously had used induced pluripotent stem cells (iPSCs) — stem cells reverse-engineered from other cell types, such as skin cells — from both PPMS patients and healthy controls to make neural progenitor cells (NPCs). Through these experiments, they obtained preliminary evidence that cells from PPMS patients were less capable of promoting OPC maturation.
Researchers hypothesized this difference might be due to cellular senescence, which, according to the team, “causes a pro-inflammatory cellular phenotype that impairs tissue regeneration, has been linked to stress, and is implicated in several human neurodegenerative diseases.”
To test their hypothesis, researchers first analyzed brains from deceased patients with and without progressive MS, including PPMS and secondary progressive MS (SPMS). They tested for the presence of molecular markers of precursor cells, and markers of senescence.
Results showed that in the progressive MS brains — specifically within demyelinated lesions — there were fewer progenitor cells, and those that were present had higher levels of senescence markers.
Researchers then returned to their iPSC/NPC model. They confirmed that NPCs derived from iPSCs from PPMS patients had more markers of senescence, compared to NPCs derived from iPSCs from healthy controls. However, both iPSCs from PPMS patients and controls had similar levels of senescence markers, suggesting that the difference occurred only after some differentiation.
We are sorry that this post was not useful for you!
Let us improve this post!
Tell us how we can improve this post?