Journal September 19, 2026 7 min read

How Collagen Synthesis Changes with Age

Collagen synthesis declines with age as dermal fibroblasts lose proliferative capacity and accumulate oxidative and glycative damage. This page reviews preclinical and clinical research on collagen-stimulating compounds,

peptides-pro Editorial

Collagen is the most abundant structural protein in the extracellular matrix (ECM), and type I collagen is the principal fibrillar collagen of the dermis; type III collagen contributes to dermal elasticity and resilience. Ageing is characterised by a progressive decline in the function of dermal fibroblasts, the primary cells responsible for collagen production and maintenance of skin structure. Over time, these cells exhibit reduced proliferative capacity, decreased collagen synthesis, and increased accumulation of oxidative and glycative damage, leading to deterioration of skin elasticity and overall tissue homeostasis [5]. Biological skin ageing also involves structural changes, including flattening of the epidermal-dermal junction and reduced collagen types I and III [2].

Research into collagen synthesis and its age-related decline centres on fibroblast growth factor (FGF) signalling, AMPK/mTOR metabolic pathways, and the modulation of extracellular matrix gene expression by bioactive peptides and small molecules [1][6].

Research Studies

Niacinamide and collagen synthesis in dermal fillers

Niacinamide is a well-established molecule that stimulates collagen synthesis, modulates inflammation and inhibits bacterial growth. A study evaluated the biostimulatory, antimicrobial, anti-inflammatory, and safety profiles of a niacinamide-enriched cross-linked hyaluronic acid dermal filler (HAR) compared to untreated controls and Belotero Balance® [2]. The research context notes that modern aesthetic medicine is shifting from volumetric enhancement toward regenerative dermal fillers, though risks of delayed inflammation or infection from post-procedural injections should be mitigated [2].

PQQ and skin bioactive properties

Pyrroloquinoline quinone (PQQ) is a water-soluble quinone derived from bacteria, known for its antioxidant properties and ability to enhance mitochondrial function. These characteristics make PQQ a promising bioactive molecule for anti-aging applications in dermatology. A study aimed to improve PQQ production by developing a UV-induced mutant strain and optimizing the culture medium, and to evaluate the potential of the produced PQQ as a cosmetic ingredient. The mutant strain, NPP-230, was compared with the wild-type strain, Hyphomicrobium denitrificans ATCC51888, for growth and PQQ production after 96 h of cultivation [3].

BPC-157 and tissue repair mechanisms

Body Protective Compound-157 (BPC-157) is a synthetic pentadecapeptide derived from gastric proteins that has demonstrated notable reparative and anti-inflammatory properties across diverse preclinical models. Experimental evidence reveals that BPC-157 supports angiogenesis, collagen synthesis, fibroblast activity, and modulation of nitric oxide pathways, contributing to enhanced healing of muscle, tendon, ligament, bone, and gastrointestinal tissue. Studies also report reduced inflammatory cytokine activity, improved microvascular integrity, and beneficial effects on pain modulation through peripheral and dopaminergic mechanisms. Although animal data indicate favorable safety and pharmacokinetic profiles, human clinical data remain limited [4].

FGF21-modified exosomes and fibroblast glycolysis

Chronic wound healing disorders remain a significant clinical challenge, largely due to the limited effectiveness of conventional therapeutic strategies. Emerging evidence suggests that engineered exosomes represent a promising cell-free therapeutic approach. A study aimed to elucidate the mechanisms by which fibroblast growth factor 21 (FGF21)-modified adipose-derived mesenchymal stem cell (ADSC) exosomes promote wound healing. ADSCs overexpressing FGF21 were established using genetic engineering, and FGF21-enriched exosomes (Exo@FGF21) were isolated and characterized using transmission electron microscopy and nanoparticle tracking analysis [1]. The work reports that FGF21-modified adipose stem cell-derived exosomes promote wound healing by activating fibroblast glycolysis through AMPK/mTOR signaling [1].

Injectable platelet-rich fibrin and bioactive peptides in dermal fibroblasts

Facial aging is a multifactorial process involving changes in bone, fat compartments, ligaments, muscles, and skin. Collagen biostimulators, including synthetic agents and autologous platelet concentrates, have gained attention for facial rejuvenation. Injectable platelet-rich fibrin (i-PRF), a second-generation autologous concentrate, has shown promising regenerative properties due to its natural composition and growth factors. Cosmetic peptides, such as palmitoyl pentapeptide-4 (Matrixyl) and Tetrapeptide-21 (GEKG), are also studied for their ability to stimulate collagen synthesis and remodel the extracellular matrix. An in vitro study examined the potential synergistic effects of i-PRF and bioactive peptides on dermal fibroblast viability and extracellular matrix gene expression [6].

Dietary supplement effects on collagen production

A clinical study evaluates the effects of a dietary supplement containing natural bioactive compounds on biological processes associated with skin ageing and extracellular matrix integrity. The study integrates in vitro and clinical approaches to investigate the potential benefits of the formulation [5]. The research context notes that ageing is characterised by a progressive decline in the function of dermal fibroblasts, the primary cells responsible for collagen production and maintenance of skin structure, with reduced proliferative capacity, decreased collagen synthesis, and increased accumulation of oxidative and glycative damage [5].

Vitamin C and collagen synthesis in chronic rheumatism

Scurvy is an almost forgotten carential pathology, caused by a deep vitamin C (or ascorbic acid) deficiency, a priori exceptional in industrialized countries. According to the French National Authority for Health standards, hypovitaminosis C is defined as a plasma vitamin C level of less than 23 μmol/L. This deficiency would affect 5 to 10% of the general population in industrialized countries and from 17% (clinical scurvy) to 47% (biological hypovitaminosis C) of vulnerable populations (malnutrition, hospitalized patients...). Vitamin C is essential for collagen synthesis. It plays a cofactor role in the synthesis of catecholamines precursors and takes action in synthesis of certain amino acids [8]. A study evaluates plasma vitamin C levels in a population of chronic rheumatism in immuno-rheumatology [8].

Dextrose injections and chronic shoulder pain

Chronic shoulder pain is a condition that typically lasts longer than three months and affects daily life. Among musculoskeletal system pathologies, shoulder pain ranks third after spine and knee pathologies. Patients with chronic shoulder pain often experience significant functional loss and reduced psychosocial well-being. Chronic shoulder pain may originate from instability, rotator cuff pathologies (calcific tendinitis, tendinopathy, full-thickness or partial tears), the acromioclavicular joint, adhesive capsulitis, or the glenohumeral joint. It results in pain, decreased joint range of motion, stiffness, limitations in activities of daily living, and ultimately disability. A study compares the effectiveness of 5% and 10% dextrose treatments in patients with chronic shoulder pain using ultrasound-guided perineural injection [7].

Type III collagen and peptide ingredient screening

Type III collagen plays a key role in maintaining skin elasticity and dermal resilience, yet its decline is associated with visible signs of skin ageing. A study aimed to establish a data-driven approach to identify cosmetic peptides with potential to enhance type III collagen through multi-target mechanistic understanding and peptide ingredient screening via biological knowledge graph and molecular docking [9].

Fisetin-functionalized DNA nanocage for aged skin wound healing

Age-related impaired wound healing presents distinct challenges compared to conventional wounds, primarily due to dysregulated phase kinetics of wound repair and chronic cellular senescence, which collectively disrupt the dynamic and orderly progression of tissue regeneration. A study reports a photo-responsive, fisetin-functionalized DNA nanocage for programmed therapy to accelerate early-stage wound healing in aged skin [10].

Bombax ceiba flower extract and antioxidant defense

Wound healing requires coordinated keratinocyte and fibroblast migration, extracellular matrix (ECM) deposition, and growth factor signaling. Disruption of these processes delays repair and impairs skin integrity. Bombax ceiba flower contains phenolic compounds with antioxidant and anti-inflammatory properties. A study reports that Bombax ceiba flower extract enhances antioxidant defense and wound healing effects in human keratinocytes and fibroblasts [11].

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