Chondroitin Sulfate Identified as an Anti-aging Compound

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Potential anti-ageing effect of chondroitin sulphate through skin regeneration​


Conclusion: Together, our results indicated that CS has the potential to facilitate skin regeneration, implying that CS could be clinically applied to improve skin ageing










Youthful and age‐related matreotypes predict drugs promoting longevity​


For instance, placing old cells into a “young” ECM rejuvenates senescent cells or stem cells and even reprograms tumor cells (reviewed in (Ewald, 2019)). Moreover, collagen homeostasis is required and sufficient for longevity in Caenorhabditis elegans (Ewald et al., 2015). Heparan/chondroitin biosynthesis and TGFβ pathway are frequently enriched in C. elegans longevity drug screens (Liu et al., 2016). Collectively, these functionally implicated genes are all members of the matrisome.


We improved drug uptake for one of our predicted compounds, genistein, and reconciled previous contradictory reports of its effects on longevity. We identified and validated new compounds, tretinoin, chondroitin sulfate, and hyaluronic acid, for their ability to restore age‐related decline of collagen homeostasis and increase lifespan. Thus, our innovative drug screening approach—employing extracellular matrix homeostasis—facilitates the discovery of pharmacological interventions promoting healthy aging.



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Question from above: "For instance, placing old cells into a “young” ECM rejuvenates senescent cells or stem cells and even reprograms tumor cells (reviewed in (Ewald)"
Is that why transplanting male pattern baldness scalp onto scid mice caused the balding cells from the human to completely grow at the same rate as normal non-balding cells?

The SCID mice were 8 weeks of age. They live 5-6 months in a non-sterile environment or 1-2 years in a sterile environment which I would think that would be more the case in the Orentreich study. Either way the human balding hair follicles were transplanted onto young ECM.
So...we need to rejuvenate the ECM or the interstitium. The ECM is contained within the interstitium so basically they are pretty much interchangable terms. This is where I left off in my last post about DMSO from midwesterndoctor.com
Chondroitin sulfate is one way to rejuvenate the ecm and therefore recreating a rejuvenating effect on "old balding" cells.


 

OtyMac

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Are we already recreating a new ECM with micro-needling? It looks that way...
 

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We know that in menopause that woman start to develop hair loss problems just like men do and could that be because of collagen atrophy?



Collagen atrophy is the main factor associated with menopause-related skin aging, which contributes to reduced skin elasticity[1
In menopause, skin thickness and collagen content are initially reduced by 1.13% and 2.1% per year respectively; type I and III collagen decrease by 30%. The skin is not only a target for sex-hormones but also produces and releases estrogen from the enzymatic conversion of estrogen precursors. Estrogen exerts a number of functions on connective tissue such as counteracting the degradation of collagen by MMPs induced by UV light and ROS through the activation of the TGF-β1 pathway. Skin and bone thickness are also positively correlated with estrogen levels. Post-menopausal women with less estrogen, show a decreased expression of TGF-β1 in skin fibroblasts, which may hamper the ability of fibroblasts to produce collagen, elastin and proteoglycans.

Dermis and adipose, muscle, bone, cartilage, and the surrounding parenchyma of organs, are all connective tissue, which highlights the relevance of the ECM in maintaining tissue homeostasis. Within the intercellular space, phenomena like cellular polarization and migration, regulation of growth factors, activation of signaling molecules, and processes translating mechanical stimulation into a chemical signal through the involvement of mechanosensitive channels are all essential for the maintenance of ECM elasticity and physiological tissue stiffness [Figure 1]. Mechano-transduction in particular, is an increasingly well-studied process

Extracellular matrix components can be divided into 3 main groups
Structural proteins​
Adhesion proteins​
Glycosaminoglycans​
Proteoglycans​
Collagen​
Fibronectin​
Ialuronan​
Biglican​
Elastin​
Fibrillin
Laminin
Tenascine
Vitronectine
Osteonectine​
Heparan-sulphate
Condroitn-sulphate
Agregacan
Versican
Neurocan​


We believe that in the near future, the ECM will be recognized as a master element of many organs and body systems, overcome the barriers and concepts of current specialty fields, and improve our mechanistic understanding of the many internal and external dysfunctions and disease states for better treatment.
 
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Low-molecular-weight collagen peptides (CPs) supplementation has recently garnered increasing attention due to its potential health benefits including hair/skin health [27,28,29,30,31,32,33]. Particularly, fish-derived CPs possess some advantages over conventional collagen sources, including a higher collagen content, environmental friendliness, low toxicity, low inflammatory response, greater absorbability due to its low molecular weight, less religious and ethical constraints, and less regulatory and quality control problems [34,35]. Patients suffering from hair loss often complain about scalp pruritus, scalp scaling, scalp irritation, undesirable hair texture, and the need to apply medication twice a day. However, research on hair growth therapies has mostly focused on direct topical treatments, whereas oral treatments have remained largely unexplored [36]. Among fish CPs, CP extracted from the scales of the Mozambique tilapia (Oreochromis mossambicus) has been reported to possess several bioactive properties such as hair cell proliferation [37], antioxidant [38], and wound healing effects [39]. In previous studies, bioactive CPs have been reported to enhance hair thickness and follicle cell proliferation, in addition to improving hair dryness and dullness [29,30,40].

Effect of CP on Cell Proliferation of Human Dermal Papilla Cell


To evaluate the safety of CP administration, the proliferation rate of hDPCs was evaluated at various concentrations of CP (Figure 1). The cell proliferation rate of the NC group was adjusted to 100 as a reference and all other treatments were reported as relative values. The CP 62.5 ppm group exhibited the highest hDPCs proliferation rate (113.98 ± 1.44%). More importantly, this value was not significantly different from the PC group. The CP 7.81–125 ppm groups exhibited similar cell proliferation rates, all of which were higher than that of the NC group (p < 0.05). CP showed a higher cell proliferation than NC at all concentrations except 3.91 ppm.

In contrast, cell proliferation rates remained high even at a high CP concentration of 250 ppm. Therefore, fish CP is considered safe within a 3.91–250 ppm range and effectively induces the anagen phase of hair follicles by promoting hDPCs proliferation.


Hair growth could be regulated by modulating the hair cycle, such as by prolonging the anagen phase and promoting the telogen-to-anagen transition [46]. The C57BL/6 mice possess melanocytes only in the hair follicles, and therefore, melanin synthesis coincides with the hair growth cycle. Thus, the hair growth cycle can be easily characterized by simply monitoring the transition of the skin color from pink (no hair) to black (fully grown hair) [48]. During the telogen phase, the dorsal skin color of the mouse was pink, but shifted to gray and black over the course of a few weeks [49]. The hair regrowth score of mice orally treated with CP was significantly higher than that of untreated mice. The black, full-grown areas were also wider in the CP-treated mice than in the controls. These findings, thus, confirm that oral intake of fish CP promotes the telogen-to-anagen transition. The size and location of hair follicles vary according to each cycle of the anagen phase, catagen phase, and telogen phase [49]. In the anagen phase, the dermal papilla and hair bulb are large and located in the deep subcutaneous tissue. In the telogen phase, however, the dermal papilla is small and the hair follicle is located in the dermis close to the epidermis [49,50]. The hair follicles in the NC group were located in the epidermis, whereas hair follicles in the CP groups were mostly located deep in the subcutaneous tissue. These observations suggest that fish CP induces the anagen phase.


The hair cycle is regulated by specific cytokines, which affect the growth of mesenchymal-cell-derived DPCs. In turn, the affected DPCs release factors that either inhibit or promote the growth of follicular epithelial cells [41,45]. IGF-1, which is widely known as a hair-growth-promoting factor, promotes the proliferation of hair follicle epithelial cells and inhibits the anagen-to-catagen transition of hair follicles. Additionally, VEGF, a known hair growth factor, has been shown to increase follicle size and hair thickness by inducing the differentiation of hair root cells through the improvement of blood circulation [41,42,43]. Conversely, TGF-β1, known as a hair growth inhibitory factor, causes hair loss by inducing apoptosis, increasing the number of telogen hair follicles, and promoting entry into the catagen phase [13,20,44,51,52]. Our findings confirmed that the mRNA expressions of IGF-1 and VEGF of the CP-treated groups were upregulated compared to the PC group, whereas TGF-β1 was downregulated. In previous studies, increased mRNA levels of IGF-1 and VEGF, and decreased levels of TGF-β1 were associated with hair-growth-promoting effects [11,53]. Many studies have evaluated the effects of several compounds in a variety of presentations (e.g., ampoules, sprays, and ointments) on hair growth. However, little is known regarding the effectiveness of orally administered compounds for the treatment of hair loss. Previous studies have demonstrated that oral CP administration can improve microcirculation and increase blood supply, which could have an effect on the metabolism of the hair cells and subsequently lead to increased hair thickness [29]. Here, we confirmed that oral fish CP administration promoted the expression of hair-growth-promoting factors while suppressing the expression of hair growth inhibitory factors, thereby affecting hair growth.


Most studies on hair loss treatment have mainly targeted topical treatments rather than oral supplementation. A few studies had preliminarily explored the effects of oral CP intake on hair growth. However, adequate nutrient intake is also critical to enhance the turnover rates and metabolic activity on hair follicles [4]. For example, keratin is a primary component of hair, and its synthesis requires adequate protein intake to maintain sufficient levels in the body. Furthermore, in a previous study, low levels of amino acids were associated with hair loss [2]. CP contains high levels of proline-hydroxyproline (Pro-Hyp) dipeptide, which enhances cell proliferation and hyaluronic acid synthesis in human dermal fibroblasts [54]. Oral administration of low-molecular-weight CP, which is a fish-derived collagen hydrolysate, regulated the synthesis of amino acids such as hyaluronic acid and hydroxyproline, thereby restoring skin damage caused by UVB irradiation and increasing skin moisture [45,46]. Moreover, fish CP promoted the recovery of collagen fibers and normal elastic fibers in the skin from degraded collagen and abnormal elastic fibers caused by UVB irradiation [55]. Another study suggested that an oral composite supplement containing fish derived-CP and ornithine improves skin conditions by increasing plasma IGF-1 levels after 8 weeks of supplementation. Specifically, IGF-1 is known to activate cell growth both during epidermal and dermal skin development and maintenance [56].


Dosages used for the mice: either 500mg/kg or 1000 mg/kg which to convert to humans divide by 12. or about 40-80 mg/kg or 4-8 grams per day for a 100 kg human.

Here are a couple sources:

 
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