Diclofenac Was Really Acting to Remove Senescent Cells

[OtyMac]

Topical Diclofenac 3% Gel for Actinic Keratosis May Induce Terminal Hair in Male Androgenetic Alopecia: A Report of Three Cases

Recently topical 3% diclofenac is commonly used to treat actinic keratosis (AK). It is proposed that it may also have a potential effect on hair growth....

brieflands.com

The researchers focused on what they thought was due to an anti-inflammatory effect. Problem with that is most/all anti-inflammatories CAUSE hair loss. The hair follicle NEEDS INFLAMMATION to begin anagen. Problem is and my pet hypothesis is that: surrounding senescent cells create an inflammatory environment to the surrounding cells(see the hair transplant video and think of what I'm saying).

The hair follicle is surrounded by "noise" of senescent inflammation then and do not respond well to normal hair inflammation signals. Too much senescence inflammation makes it difficult to pick up any normal inflammation which would start up anagen again.

The conclusion can be one and only one and that is diclofenac was acting like a senolytic agent clearing out actinic keratoses(which are composed of senescent cells) but also even deeper down into the hair follicle probably wiping out senescent dermal papilla.

There is NO WAY that the guy could have been still regrowing hair __4 YEARS_ after the treatment ended if we were just blocking COX-2 pathways..



Diclofenac is terribly damaging to the mitochondria and that is why it was used in the first place.

Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria: Possible role in drug induced liver injury (DILI) - PubMed

Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation of the...

pubmed.ncbi.nlm.nih.gov

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Actinic keratosis (AK) is a precancerous skin condition that can be treated with senolytic drugs. Senolytic drugs are currently being tested in clinical trials for several age-related diseases and some cancers.

 

[OtyMac]

So..those people that thought they would regrow hair WHILE using diclofenac is counter productive. The mitochondria is being damaged so it will not produce any hair UNTIL the treatment is over as the guys(in the study) above found out.

You can also find the same thing about 5-fluororuracil which the guy was regrowing hair months after the treatment for actinic keratoses was over.
I will locate the study later...

 

[OtyMac]

Another thing that could be useful against actinic keratoses(which are senescent precancerous cells) is oral nicotinamide.

Oral Nicotinamide Reduces Actinic Keratoses in Phase II Double-Blinded Randomized Controlled Trials | 10.1038/jid.2011.459_Science Hub

www.tesble.com

The mechanisms by which nicotin-
amide might prevent skin cancer or
reduce progression of subclinical lesions
are unclear. Nicotinamide is a substrate
and inhibitor of the nuclear enzyme
poly-ADP-ribose polymerase, which is
centrally involved in DNA repair (Virag
and Szabo, 2002). As a precursor of
nicotinamide adenine dinucleotide,
nicotinamide prevents the decline in
cellular energy observed after UV expo-
sure (Park et al., 2010), and could
therefore maintain efficient DNA repair
__________________________________________

Optimizing the energy status of skin cells during solar radiation - PubMed

Ionizing- and ultraviolet-radiation cause cell damage or death by directly altering DNA and protein structures and by production of reactive oxygen species (ROS) and reactive carbonyl species (RCS). These processes disrupt cellular energy metabolism at multiple levels. The formation of DNA...

pubmed.ncbi.nlm.nih.gov

Ionizing- and ultraviolet-radiation cause cell damage or death by directly altering DNA and protein structures and by production of reactive oxygen species (ROS) and reactive carbonyl species (RCS). These processes disrupt cellular energy metabolism at multiple levels. The formation of DNA strand breaks activates signaling pathways that consume NAD, which can lead to the depletion of cellular ATP. Poly(ADP)-ribose polymerase (PARP-1) is the enzyme responsible for much of the NAD degradation following DNA damage,

 

[OtyMac]

Here is another thing senescent cells do and I think PROVES the existence of senescence in Androgenetic Alopecia.

Wounding Therapies for Prevention of Photocarcinogenesis - PubMed

The occurrence of non-melanoma skin cancer (NMSC) is closely linked with advanced age and ultraviolet-B (UVB) exposure. More specifically, the development of NMSC is linked to diminished insulin-like growth factor-1 (IGF-1) signaling from senescent dermal fibroblasts in geriatric skin...

pubmed.ncbi.nlm.nih.gov

The occurrence of non-melanoma skin cancer (NMSC) is closely linked with advanced age and ultraviolet-B (UVB) exposure.(think about the hats study)(UVA can reach dermal papilla but UVB can't but it still shows the mechanism of damaged DNA repair by limiting IGF-1 responsiveness. Think about it: if the cell is damaged should it be allowed to proliferate by allowing IGF-1 to cause it to do so?

More specifically, the development of NMSC is linked to diminished insulin-like growth factor-1 (IGF-1) signaling from senescent dermal fibroblasts in geriatric skin.

What happens with diminished IGF-1 levels or reduced sensitivity?(again thanks to Benjit)

https://www.gourmetstylewellness.com/interact/threads/linking-the-von-mises-mechanical-stress-models-and-insulin.132212/

Consequently, keratinocyte IGF-1 receptor (IGF-1R) remains inactive, resulting in failure to induce appropriate protective responses including DNA repair and cell cycle checkpoint signaling


Do these sound familiar to anybody?

In this review, we highlight the pathogenesis of NMSC and discuss the potential of novel preventative therapies.

In particular, wounding therapies such as dermabrasion, microneedling, chemical peeling, and fractionated laser resurfacing(https://pubmed.ncbi.nlm.nih.gov/?term=fractionated+laser+alopecia) have been shown to restore IGF-1/IGF-1R signaling in geriatric skin and suppress the propagation of UVB-damaged keratinocytes. This wounding response effectively rejuvenates geriatric skin and decreases the incidence of age-associated NMSC.

 

[OtyMac]

How to recreate a disease? Inject senescent cells into that area..

We are not dealing with arthritis of course but the mechanisms are probably very similar in that senescent cell inflammation instigates damages to surrounding cells. So..Squeegee was correct, "anything that stops arthritis inflammation will help male pattern baldness" or anything that stops SASP inflammation will help male pattern baldness which could include using senolytics(NK cell stimulation too) or just accepting senescent cells will exist and just dealing with the inflammation from it.

Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice - PubMed

Osteoarthritis (OA) is the leading form of arthritis in the elderly, causing pain, disability, and immobility. OA has been associated with accumulation of senescent cells in or near joints. However, evidence for a causal link between OA and cellular senescence is lacking. Here, we present a...

pubmed.ncbi.nlm.nih.gov

 

[OtyMac]

Is IGFBP7 from senescent cells blocking the hair growth effects of IGF-1?

IGFBP7 is a key component of the senescence-associated secretory phenotype (SASP) that induces senescence in healthy cells by modulating the insulin, IGF, and activin A pathways - Cell Communication and Signaling

Senescent cells exert their effects through the release of various factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The SASP can induce senescence in healthy cells (secondary senescence), modulate immune system function, reshape the extracellular matrix...

biosignaling.biomedcentral.com

IGFBP7 can bind insulin growth factor receptor 1 (IGF1R) and can inhibit its interaction with IGF ligands.

 

[OtyMac]

Also look into the jak inhibitor study on gourmetstylewellness.com which reduce sens cells by reducing activin A.

Like Squeegee said..whatever works for arthritis will work for male pattern baldness and jak inhibitors work for arthritis.Two seemingly distinct diseases with the same etiology; senescent cell inflammation.

IGFBP7 is a key component of the senescence-associated secretory phenotype (SASP) that induces senescence in healthy cells by modulating the insulin, IGF, and activin A pathways - Cell Communication and Signaling

Senescent cells exert their effects through the release of various factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The SASP can induce senescence in healthy cells (secondary senescence), modulate immune system function, reshape the extracellular matrix...

biosignaling.biomedcentral.com