Defending Against Thermal Aging: How Donkey Milk miRNAs Mitigate Heat-Induced Skin Stress

As global temperatures continue to fluctuate, environmental skincare is shifting focus from ultraviolet (UV) radiation to a concurrent, often overlooked threat: thermal aging. Prolonged exposure to ambient heat compromises skin barrier function, accelerates collagen degradation through the upregulation of matrix metalloproteinases (MMPs), and triggers cellular apoptosis (programmed cell death).

While traditional skincare relies on topical coolants to temporarily lower skin temperature, advanced cellular biology points toward a genetic solution found within donkey milk whey: stress-responsive microRNAs (miRNAs). These microscopic regulatory molecules serve as epigenetic shields, protecting skin cells from heat-induced collapse.

1. Thermal Aging and Cellular Homeostasis

When skin is subjected to high ambient temperatures, it experiences a physiological state known as heat stress. At the cellular level, this stress disrupts the delicate balance of the extracellular matrix.

• MMP Upregulation: Heat stress increases the expression of enzymes that aggressively break down collagen and elastin fibers, leading to premature sagging and deep wrinkling.
• Apoptosis Activation: Severe or prolonged thermal stress triggers intracellular signaling cascades that lead to structural failure and cell death in dermal fibroblasts and epidermal keratinocytes.

To counteract this degradation, cells require regulatory interventions that can fine-tune gene expression in real-time, restoring homeostasis before permanent structural damage occurs.

2. The Abundance of Environmental Adaptation Codes in Donkey Milk

Donkey milk stands out as a unique repository of genetic material. Recent comparative transcriptomic analyses have shown that donkey milk contains an exceptionally high concentration of small non-coding RNAs compared to traditional dairy sources.

Research confirms that microRNAs account for 7.74% of the total annotated RNA in donkey milk, compared to a mere 1.57% in goat milk, 1.12% in sheep milk, and 0.87% in buffalo milk.

This rich genetic profile includes highly conserved livestock adaptation miRNAs—such as the miR-29 family (including miR-29b) and miR-15a—which are naturally expressed by the animal to modulate systemic homeostasis, immune response, and environmental adaptation. When delivered via protective extracellular vesicles (EVs) or milk whey, these miRNAs remain highly stable and bioactive, capable of penetrating the outer layers of the skin.

3. Molecular Mechanisms: Inhibiting Heat-Induced Apoptosis

At the molecular level, donkey milk miRNAs act as post-transcriptional regulators. They bind to specific messenger RNAs (mRNAs) within human skin cells to suppress the damaging pathways activated by thermal stress.

• Suppression of Pro-Apoptotic Pathways: Under heat stress, cells normally upregulate pathways that dictate cell death. Specific stress-responsive miRNAs in donkey milk downregulate these pro-apoptotic signaling cascades, effectively keeping the cell survival switches turned "on."
• Mitigation of Oxidative and Inflammatory Cascades: Thermal stress often triggers an immediate oxidative burst. The collective action of donkey milk miRNAs assists in stabilizing the Nrf2-mediated antioxidant pathway, enhancing the cell’s internal defense mechanisms against oxidative injury.
• Collagen Preservation: By stabilizing cellular health and mitigating the inflammatory signaling that follows heat exposure, these miRNAs indirectly suppress the overproduction of collagen-destroying MMPs, preserving the skin's structural integrity.

By delivering an abundant, stable matrix of adaptation-related miRNAs, donkey milk-based formulations offer a sophisticated genetic approach to mitigating thermal aging—shifting the paradigm from passive skin cooling to active cellular defense.

References & DOI

• Cendron, F., et al. (2024). Analysis of miRNAs in milk of four livestock species. BMC Genomics, 25:859.
  • DOI: 10.1186/s12864-024-10783-4
• Çelik, A., Vural, A., & Yıldırım, İ. H. (2025). Detection of miRNA-15a, miRNA-29b, miRNA-34a and miRNA-223 in Cow, Sheep, Goat, Buffalo, and Donkey Milk and Investigation of Their Relationship with Milk Composition. Journal of the Hellenic Veterinary Medical Society, 76(2), 9375–9384.
  • DOI: 10.12681/jhvms.39515
• Giosuè, C., et al. (2021). Transcriptomic Characterization of Cow, Donkey and Goat Milk Extracellular Vesicles Reveals Their Anti-inflammatory and Immunomodulatory Potential. International Journal of Molecular Sciences, 22(22), 12344.
  • DOI: 10.3390/ijms222212344