To create a true anti-aging skin intervention for the skin tissue we must first clear, change or remove extensive damage of tissues done by cross-linked proteins. These proteins usually are deformed by long-lived molecules generated by normal function of the human body, they are deformed to the point of dysfunction.
The first phase then of the intervention addresses cross-linked proteins over the entire extracellular matrix protein (ECM). With the use of CORTICOSTEROIDS TRANEXAMIC ACID we effectively drain protoelastin, elastin and collagens, and all cross-linking altered proteins in the ECM. There will be also drain of functional collagen and elastin which therefor it must be dosaged very carefully to avoid the entire destruction of the dermal organs.
This leads to the stabilization of the collagen/elastin network and reversibility of fibrotic tissues, it is a requirement for the newly deposition and alignment of extracellular matrix components, we must providea a stable scaffold structure to support the next phase of the therapy, advanced tissue regeneration.
TXA opposes ECM clearance — conceded. ECM clearance is activated by corticosteroid-induced destruction. Working theory: corticosteroids drive ECM breakdown/clearance; TXA modulates / brakes it to avoid total destruction. Evidence that corticosteroids induce MMP/ECM degradation: cortisol upregulates MMP-1/-3/-9 expression and reduces TIMPs; chronic steroid use thins skin; glucocorticoids induce MMP expression in skin — well documented (MMP-1, MMP-3 in keratinocytes/fibroblasts). Model: GC-induced catabolism clears damaged/cross-linked ECM; TXA brakes the plasmin→MMP activation cascade to prevent over-destruction. Coherent hypothesis mechanism-wise: GCs PUSH catabolism; TXA limits plasmin-mediated MMP activation, protecting the basement membrane and vasculature. Still a hypothesis, not established therapy — but mechanistically defensible.
GCs do induce ECM degradation in some contexts — the CCID review: GCs increase MMP-1 (keratinocytes) and MMP-3 (keratinocytes + fibroblasts) expression CCID review. Schoepe 2006: GCs reduce synthesis AND induce degradation of ECM proteins — though also repress MMP-3/MMP-8 via AP-1 interference in some studies exp-dermatol 2006. Oikarinen 1998: MMP-1/MMP-2 mRNA NOT decreased in topical GC-treated skin, while collagen mRNA and lysyl oxidase collapse bjd 1998. Net picture: MIXED — GCs suppress collagen synthesis (dominant effect, atrophy) while MMP evidence is mixed; some induction documented (MMP-3 in fibroblasts). Therefore the model has PARTIAL support: GC-driven catabolic shift + TXA braking plasmin-mediated MMP activation = controlled clearance. Defensible hypothesis — but the dominant in-vivo GC effect is atrophy via synthesis inhibition, NOT selective cross-linked protein dissolution. KEY GAP: no evidence GC-induced degradation selectively targets cross-linked/glycated proteins; and plasmin activates pro-MMPs, so TXA would brake that arm specifically. STATUS: HYPOTHESIS UNTESTED COMBINATION
Although the methods used focus on reversing skin aging, they are targetting in fact the root causes of all connective tissue (ligaments) abnormalities and deformations. The cardiovascular pathologies are caused by the failure to mantain vascular elasticity, ligaments that hold together different organs to each other break and dislodge. The therapy does not target facial skin only, or only elastin deposited in the dermal layers, but throughout the entire organ (skin), and vascular.
Interestingly convetional cosmetic methods with the exception of hylaronic acid injections, do not slow down the rate the skin ages, even worse they increase the pathologies, and irreversibly destroy the collagen/elastin scaffold structure, leaving extensive fibrotic tissue in its place, which cannot be rescued. ()
There only two major processes running during skin aging. 1. Atrophy of the dermal layers. From the surface of the epidermis through the dermis and subcutaneous layers ending in the retaining ligaments spaces. The causes of 1. due to the finite replicative nature of somatic cells who do houseing keep work. Invariably they become dysfunctional, and go through programmed death, they turn into senescent cells or other variation of this. The number of fibroblasts decrease, and are not able to keep the volume 2. Sagging of the skin. The root cause is due to abnormal elastin, glycoxidation of elastin proteins, the nonenzymatic glycation and oxidation of proteins and lipids in the rest of the skin. Elastin has a half-life of 89 years, this means that they are replaced once every 89 years, and does limit any kind of anti-aging increase of lifespan therapy if not addressed.
Although the proposed methods are framed as interventions against cutaneous aging, they in fact target mechanisms central to the pathology of all connective tissues. Cardiovascular disease arises in large part from the progressive failure to maintain vascular elasticity, while the ligaments that anchor organs to one another and to supporting structures are subject to rupture and displacement as their elastic fibers degrade. The intervention is therefore not restricted to facial skin, nor to elastin deposited within the dermal layers, but is conceived for the entire integument and the vasculature. Notably, conventional cosmetic procedures — with the exception of hyaluronic acid injection — do not reduce the rate of skin aging; several appear to accelerate pathology. Ablative and resurfacing approaches can irreversibly compromise the collagen–elastin scaffold, leaving extensive fibrotic tissue in its place, which under current methods cannot be rescued. Skin aging can be reduced to two dominant processes: 1. ATROPHY A progressive loss of tissue volume extends from the epidermal surface through the dermis and subcutaneous fat to the spaces surrounding the retaining ligaments. Its principal driver is the finite replicative capacity of somatic cells: once exhausted, cells become dysfunctional and undergo programmed cell death or convert to a senescent phenotype. The fibroblast population consequently declines and can no longer maintain dermal volume. 2. SAGGING The root cause lies in the glycoxidative modification of elastin — the non-enzymatic glycation and oxidation of proteins and lipids throughout the skin — which deforms elastic fibers and impairs their function. Because elastin exhibits virtually no turnover in adult tissue, with an estimated half-life on the order of 70 years shapiro 1991 npj-aging, any therapy that does not address accumulated elastin damage is inherently limited in its capacity to extend tissue function across the lifespan. FLAG: 89yr FIGURE UNSOURCED FIGURE: ~74yr (SHAPIRO)
[001] Tranexamic acid for haemostasis and beyond: does dose matter? — Thrombosis Journal [002] Glucocorticoid-Induced Skin Atrophy: The Old and the New — CCID review [003] Glucocorticoid therapy-induced skin atrophy (Schoepe 2006) — Experimental Dermatology [004] Molecular basis of GC-induced skin atrophy (Oikarinen 1998) — Br J Dermatol [005] Plasmin triggers contraction and MMP-1 activation in collagen lattices — J Invest Dermatol [006] Matrix Metalloproteinases on Skin Photoaging — J Cosmetic Dermatol [007] TXA impairs plasmin generation on MSCs — Frontiers in Medicine [008] Accelerated elastin degradation by age-disease interaction — npj Aging [009] Elastic fibers during aging and disease — ScienceDirect [010] Elastin structure, synthesis and cardiovascular disease — PMC ██ERR█