Skin

The body's largest organ and its most visible record. Collagen, elastin and barrier lipids degrade on a measurable schedule — and the evidence shows the degradation mechanisms specifically, because that is what the evidence actually witnesses.

Tissue remodeling increases it.

Dermal-aging review 2019, Int J Mol Sci — dermal collagen provides the skin's mechanical support and elasticity; collagen loss drives dermal atrophy and wrinkling. PMC6540032

Oxidative stress reduces it.

Photoageing is an oxidative process, and it acts on the same endpoint the procollagen lane above measures. UV exposure raises ROS, which up-regulates the matrix metalloproteinases (MMP-1, -3, -9) that degrade collagen, elastin and fibronectin — producing deep wrinkles and sagging (PMC8597149, PMC9988502). So the two lanes into this pathway are two ends of one balance: synthesis versus degradation. Verbatim: “Increased ROS levels due to PM exposure critically damage the respiratory and cardiovascular systems, other organs, and skin”. doi 10.7717/peerj.16589 · PMC8597149

Strengthens veins increases it.

10.1080/07853890.2026.2694142 — https://www.merckmanuals.com/professional/cardiovascular-disorders/peripheral-venous-disorders/chronic-venous-insufficiency-and-postphlebitic-syndrome — Venous stasis causes dermatitis and ulceration - the classic distal presentation. doi 10.1080/07853890.2026.2694142

Women's hormone balance increases it.

Collagen and elastin loss is systemic, not only urogenital. PMC10692865

Absorption increases it.

Verbatim: “Furthermore, in mice, Gly-3Hyp-4Hyp was efficiently delivered to the skin after jellyfish collagen hydrolysate administration, showing a 19-fold greater accumulation compared with the bovine group, whereas other Hyp-containing oligopeptides exhibited minimal transport”. doi 10.1021/acs.jafc.6c08326 · PMID 42715523

Cell migration switch reduces it.

Verbatim: “EMT may be involved in keloid generation and/or aggravation and may have potential as a keloid treatment target”. doi 10.1097/GOX.0000000000001138 · PMID 27975033 · PMC5142499

Allergic signaling reduces it.

10.3389/fmed.2023.1165098 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). Verbatim: “IL-4 and IL-13 do inhibit the expression of IVL, LOR, FLG, and FLG2 in keratinocytes in vitro”. doi 10.3389/fmed.2023.1165098 · PMC7432778

Inflammatory signaling reduces it.

10.1038/s41467-025-63791-7 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). Verbatim: “The IL-17-family cytokines IL-17A and IL-17C drive the pathogenesis of psoriatic skin inflammation, and anti-IL-17A Abs were recently approved to treat human psoriasis”. doi 10.1038/s41467-025-63791-7 · PMID 27920272 · PMC5225040

Calms body-wide inflammation reduces it.

10.3390/ijms24097784 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). Verbatim: “In conclusion, PMs induce the expression of pro-inflammatory cytokines in keratinocytes via the p38 MAPK pathway, and these interleukins increase the expression of MMP1 and COX2 in HDF cells”. doi 10.3390/ijms24097784

Antioxidant defense increases it.

10.3390/nu9121371 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). doi 10.3390/nu9121371

DNA integrity reduces it.

10.3390/cosmetics12040172 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). doi 10.3390/cosmetics12040172

Clears worn-out cells reduces it.

10.3389/fphys.2023.1297637 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). doi 10.3389/fphys.2023.1297637

Reduces scarring reduces it.

10.1038/s41598-020-74179-6 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). A 1990 study on this pathway reports that, unlike retinoids, TGF-beta acts on mitotically active basal cells to slow their proliferation. doi 10.1038/s41598-020-74179-6 · PMC361689

Estrogen balance increases it.

10.3390/life16030401 — The aging outcome lists the thirteen hallmarks themselves, each mapped to its pathway and labeled with its hallmark number. (from the reviews of this outcome). Verbatim: “Many of these effects can be reversed by estrogen replacement which increases epidermal hydration, skin elasticity and skin thickness as well as reducing skin wrinkles and augmenting the content and quality of collagen and the level of vascularisation”. doi 10.3390/life16030401 · PMID 24194966 · PMC3772914

It reduces Calm skin barrier.

The barrier is not downstream - it is half the loop. Defects in skin barrier-related molecules interact with the polarization of T cells, which forms a skin barrier-inflammatory loop with them. This loop contributes to the chronicity of the primary disease OR the transition between psoriasis and AD. IL-4 and IL-13 potently inhibit filaggrin, LORICRIN and INVOLUCRIN by activating STAT6 and STAT3 - the cytokines break the barrier, the broken barrier admits more allergen, more allergen drives more cytokine. doi 10.3389/fimmu.2025.1541776 · PMC11007107

It reduces Balanced skin cell turnover.

Named across six reviews of atopic dermatitis and psoriasis as part of the shared barrier-inflammation mechanism set. doi 10.3389/fimmu.2025.1541776 · PMC11007107

It reduces Clears blocked nose & sinuses.

This is the same axis as eczema, and it splits the same way: type 2 endotypes are IL-4/IL-5/IL-13-driven and eosinophilic, while non-type-2 endotypes ARE driven by increased Th1 and Th17 responses, resulting in elevated neutrophil levels. Two endotypes, two cell types, two nodes. And the intervention evidence is unusually direct: dupilumab (IL-4Ralpha inhibitor) reduces polyp burden and restores smell, while MEPOLIZUMAB (anti-IL-5) and OMALIZUMAB (anti-IgE) address specific endotypes - three biologics, three targets, three endotype-matched responses. PMC11059040

It reduces Eases allergy load.

This is the same axis as eczema, and it splits the same way: type 2 endotypes are IL-4/IL-5/IL-13-driven and eosinophilic, while non-type-2 endotypes ARE driven by increased Th1 and Th17 responses, resulting in elevated neutrophil levels. Two endotypes, two cell types, two nodes. And the intervention evidence is unusually direct: dupilumab (IL-4Ralpha inhibitor) reduces polyp burden and restores smell, while MEPOLIZUMAB (anti-IL-5) and OMALIZUMAB (anti-IgE) address specific endotypes - three biologics, three targets, three endotype-matched responses. PMC11059040

It increases Resists infection.

The headline on this pathway is a disappointment and it must stay there: the lack of effect of prophylactic vitamin C supplementation on the incidence of common cold in normal populations throws doubt on the utility of this wide practice. Regular supplementation decreases cold duration by 8 percent (3-12) and severity by 15 percent (CI 9-21) - but does not reduce how often you get one. With one striking exception that defines WHO it works for: a subgroup of six studies of marathon runners, skiers, and soldiers exposed to significant cold AND/OR physical stress experienced, on average, 50 percent reduction in common cold incidence. Extreme physical stress is the condition under which it prevents. PMC10712193

It increases Gum health.

The mechanism is a self-feeding loop and the fuel is your own tissue: inflammation and dysbiosis positively reinforce each other because inflammatory tissue breakdown products ARE used as nutrients by the dysbiotic microbiota - specifically collagen peptides and heme-containing compounds. The bacteria eat the damage the immune response causes, which causes more damage. And it is not an infection in the ordinary sense: periodontitis is caused mainly by dysbiosis of the bacterial community, rather than an infection by individual bacteria. Keystone pathogens, whose colonization is facilitated by accessory pathogens, initially subvert the host response, after which PATHOBIONTS - commensals turned pathogenic - over-activate inflammation. A keystone pathogen works at low abundance by changing the community, not by dominating it. The tissue-destruction route is specific: pathogens induce epithelial-mesenchymal transition via TGF-beta/Smad, Wnt/beta-catenin and Notch, causing loss of E-cadherin, junctional epithelial instability, pocket formation and attachment loss. doi 10.3390/jmp7010011 · PMID 25534621 · PMC5646588

It increases Wound healing.

The critical point is a switch, not a level: the transition from an initial inflammatory phase to a proliferative phase is a critical regulatory point that determines wound healing outcomes, and macrophages drive it by switching from pro-inflammatory M1 to anti-inflammatory M2. When proinflammatory M1 macrophages persist without transitioning to anti-inflammatory phenotypes, this contributes to impaired wound healing. Which means anti-inflammatory is not uniformly good here: an ordered and well-controlled inflammatory phase is essential for the normal progression of healing. Suppressing the M1 phase does not accelerate repair - it stalls it. The requirement is timely transition, not less inflammation. Four phases, sequence-critical: hemostasis, inflammation, proliferation, remodeling - for a wound to heal successfully, these four phases must occur in an appropriate sequence and time frame. And an unexpected mechanism worth keeping: disruption of the epithelium generates a directional electrical field, which helps orient keratinocytes for directed migration. doi 10.3390/cells14231850 · PMC8432991

It reduces Clear skin.

10.12659/MSM.945336 — Drawn from reviews of neighboring outcomes rather than from studies of this outcome itself, which is weaker evidence, and the map marks it so. doi 10.12659/MSM.945336

It increases Supports airflow & lung function.

10.3389/fimmu.2026.1916940 — Drawn from reviews of neighboring outcomes rather than from studies of this outcome itself, which is weaker evidence, and the map marks it so. doi 10.3389/fimmu.2026.1916940

It increases Nails.

NBK559260 — Drawn from reviews of neighboring outcomes rather than from studies of this outcome itself, which is weaker evidence, and the map marks it so.

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