senescence-associated secretory phenotype

[IDW2BB]

Reading a couple of studies regarding premature senescence of the balding dermal papilla and so I looked into senescence a little more.
I found some info. on "senescence-associated secretory phenotype". This just makes me think that there is no way to recover or "awaken" follicles that have been lost. In fact, I wonder if the presence of the dead follicle is actually proliferating further hair loss. I wonder if removing the senescent dermal papilla would help matters?

 

[Sparky4444]

In fact, I wonder if the presence of the dead follicle is actually proliferating further hair loss.

I've wondered about that...it seems to make sense to me that it's almost like a domino effect -- I wonder if you were to halt, say, you're temples, then would loss still occur behind the temples?? Or do the temples need to fail before further loss occurs along the "front"...

 

[IDW2BB]

I've wondered about that...it seems to make sense to me that it's almost like a domino effect -- I wonder if you were to halt, say, you're temples, then would loss still occur behind the temples?? Or do the temples need to fail before further loss occurs along the "front"...

interesting study to read. while not about hair, it is a skin condition.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608562/

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http://www.ncbi.nlm.nih.gov/pubmed/24472138

Telomeres, oxidative stress and inflammatory factors: partners in cellular senescence?

Correia-Melo C, Hewitt G, Passos JF.

Abstract

Senescence, the state of irreversible cell-cycle arrest, plays paradoxical albeit important roles in vivo: it protects organisms against cancer but also contributes to age-related loss of tissue function. The DNA damage response (DDR) has a central role in cellular senescence. Not only does it contribute to the irreversible loss of replicative capacity but also to the production and secretion of reactive oxygen species (ROS), and bioactive peptides collectively known as the senescence-associated secretory phenotype (SASP). Both ROS and the SASP have been shown to impact on senescence in an autocrine as well as paracrine fashion; however, the underlying mechanisms are not well understood. In this review we describe our current understanding of cellular senescence, examine in detail the intricate pathways linking the DDR, ROS and SASP, and evaluate their impact on the stability of the senescent phenotype.

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Free access


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847322/

The plethora of signals that activate the ERK pathway and its numerous substrates suggest that the fine control of the spatiotemporal regulation of ERK activity is critical for determining opposite cell fates.20 Activation of cytoplasmatic ERK 1/2 through its phosphorylation leads to nuclear translocation thus allowing the interaction with specific nuclear substrates and the induction of specific programs of gene expression. The regulation of ERK nucleo-cytoplasmic trafficking modulates the transfer efficiency of the signaling carried by activated ERK to the cell.20 Accumulating evidences show that nuclear relocalization of active ERK is impaired in senescent human fibroblasts, and that this dysregulation may account for the irreversible proliferative arrest of senescent cells.20 The impaired nuclear localization of active ERK and the loss of proliferative potential have been proposed to originate from either impaired nuclear import or from ERK inactivation. This interpretation is supported by the high activity of the nuclear ERK phosphatase MKP2/DUSP4 in senescent cells.21

Our results also attest a dysregulation of active ERK localization in stem cell senescence program, as a lower amount of nuclear versus cytoplasmic pERK is revealed in senescent MSC together with a decrease of nuclear pERK in P10 versus P1 MSC (Figure 5c). This finding strongly supports previous studies and further delineates an unexpected complexity of ERK signaling mechanisms in cellular senescence.20 Indeed, we might envisage a scenario in which the nuclear/cytosolic localization of active ERK may be related to the MSC senescent phenotype as previously demonstrated for human fibroblasts.

Although more extensive studies are needed to expand our knowledge on the mechanisms underpinning the impaired ERK nucleo-cytoplasmic trafficking in stem cells, we also believe that our results pave the way to further investigations aiming to modify, in the near future, the current in vitro MSC expansion protocols for therapeutic purposes, thereby preventing or reducing the occurrence of negative senescence-related effects, and to better understand the complex process of senescence and aging in stem cells.