Oxidative Stress–Associated Senescence in Dermal Papilla Cells of Men with AGA

[lacazette]

Oxidative Stress–Associated Senescence in Dermal Papilla Cells of Men with Androgenetic Alopecia

http://www.nature.com/jid/journal/v1...id201528a.html

"Dermal papilla cells (DPCs) taken from male androgenetic alopecia (AGA) patients undergo premature senescence in vitro in association with the expression of p16INK4a, suggesting that DPCs from balding scalp are more sensitive to environmental stress than nonbalding cells. As one of the major triggers of senescence in vitro stems from the cell “culture shock” owing to oxidative stress, we have further investigated the effects of oxidative stress on balding and occipital scalp DPCs. Patient-matched DPCs from balding and occipital scalp were cultured at atmospheric (21%) or physiologically normal (2%) O2. At 21% O2, DPCs showed flattened morphology and a significant reduction in mobility, population doubling, increased levels of reactive oxygen species and senescence-associated β-Gal activity, and increased expression of p16INK4a and pRB. Balding DPCs secreted higher levels of the negative hair growth regulators transforming growth factor beta 1 and 2 in response to H2O2 but not cell culture–associated oxidative stress. Balding DPCs had higher levels of catalase and total glutathione but appear to be less able to handle oxidative stress compared with occipital DPCs. These in vitro findings suggest that there may be a role for oxidative stress in the pathogenesis of AGA both in relation to cell senescence and migration but also secretion of known hair follicle inhibitory factors."



Can't research right now but I know there are good ways to reduce this oxidative stress (chemicals like troxerutine,etc and naturals,..) , and based on this study with the differences between occipital and balding scalp OS effects, it seems that we should not underestimate this aspect cause it's aggravating and accelerating the balding process

troxerutine could be the one to add to our regimen but there's maybe stronger things , let's see

[Seuxin]

Thanks a lot for your work french friend !

[Swooping]

Androgen Receptor Accelerates Premature Senescence of Human Dermal Papilla Cells in Association with DNA Damage

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828374/

Here, we showed a previously unidentified relationship between androgen/AR signaling and induction of premature senescence in association with DNA damage and p16INK4a upregulation in DPCs. Our study highlights the importance of androgen/AR-accelerated premature senescence in DPCs, a process that is thought to reflect irreversible cell growth arrest in the progression of AGA. The acceleration of premature senescence of DPCs by androgen/AR signaling may explain the miniaturization of hair follicles shown in AGA patients. These results provide novel impacts of androgen/AR signaling in balding DPCs and offer the potential therapeutic targets on combating for AGA.

[champpy]

I can always depend on you, swooping, to give me something to ponder. I too will try to look at ways to lower OS later on tonight. Good find man!

[epipapilla]

The big question is why do people who do not have a genetic predisposition to pattern hair loss not suffer from oxidative stress in their dermal papilla cells, or if they do, what is protecting their hair follicles from becoming miniaturised?

[Baby John]

It's nice to see more researchers taking a look at this mechanism and it's end game effects on aga.

Swoop and a fella named Qwan Lee have been posting on this for a year or more and it's become the focal point in the way I'm personally looking at aga.

It ties in with the 30 month window, declining dpc population and disruption of niche signaling.
It offers a good explanation why aga peeps do not repopulate dpc's once they are depleted past roughly the 50% mark. All down hill after that.
It ties in with the "too much anti-oxidants are bad for you" hypothesis going around now. Higher levels of glutathione and catalase aren't enough to prevent the damage but are enough to prevent autophagy. So now this handful of cells just sits there literally signalling a stop to dpc proliferation.
It ties in with how any treatment based on brute force signalling will most likely require the user to stay on the treatment indefinitely.

It appears the only way to to reset the whole regrowth process in anyone outside the 30 month window is to destroy these cells. Then hopefully a maintenance program will keep it.

[burtandernie]

Yeah there are still big questions as to why the rare man even in his 50s can have no hair loss whatsoever. They exist, and if they do why do these theories like oxidative stress in their DP cells not affect them but do hit the rest of us? Personally the longer this goes on the more I think MPB wont be cured for many decades or even not in our lifetimes. Its going to evolve much like it has in the past very slowly over decades. Keeping your hair is the most safe bet. Heck take fin like candy and use RU when your 20 just in case you start losing hair whether you needed it or not because regrowing might not ever happen

[ShookOnes]

Yeah there are still big questions as to why the rare man even in his 50s can have no hair loss whatsoever. They exist, and if they do why do these theories like oxidative stress in their DP cells not affect them but do hit the rest of us? Personally the longer this goes on the more I think MPB wont be cured for many decades or even not in our lifetimes. Its going to evolve much like it has in the past very slowly over decades. Keeping your hair is the most safe bet. Heck take fin like candy and use RU when your 20 just in case you start losing hair whether you needed it or not because regrowing might not ever happen

hey man, don't be so down. 20 years is very possible!

[Baby John]

My bad earlier, you don't want to destroy these cells (apoptosis). You want to remove/repair damaged/malfunctioning components of the cell and restore it(hormesis/autophagy). Probably how cd, benoxaprofen and fluorouricil have caused hair growth in some late phase aga peeps. Brutal method though...