Fermented Porcine Placenta and Its Dipeptides Modulate Cellular Senescence in Human Keratinocytes

Area of Science:

• Dermatology and Cellular Biology
• Biochemistry and Molecular Biology
• Aging Research

Background:

• Skin aging is characterized by oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation.
• Senescence in human epidermal keratinocytes (HEKs) contributes significantly to the aging process.
• Understanding modulators of keratinocyte senescence is crucial for developing anti-aging interventions.

Purpose of the Study:

• To investigate the anti-senescence effects of fermented porcine placenta (FPP) and its constituent dipeptides, leucine-glycine (LG) and proline-hydroxyproline (PH), in HEKs.
• To compare the efficacy of FPP and its dipeptides with nicotinamide mononucleotide (NMN) in modulating NAD+-related pathways.
• To elucidate the specific mechanisms by which FPP and its dipeptides impact cellular senescence.

Main Methods:

• HEKs were treated with FPP, LG, PH, and NMN to assess anti-senescence effects.
• Senescence-associated β-galactosidase (SA-β-gal) activity and p16 expression were measured.
• Adenosine triphosphate (ATP) production, NAD+/NADH ratio, and enzyme activities (NQO1, SIRT1, SIRT3) were quantified.
• Sirtuin 1 (SIRT1)-peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling was analyzed.

Main Results:

• FPP significantly suppressed SA-β-gal activity and p16 expression, indicative of reduced senescence.
• FPP enhanced ATP production and activated SIRT1-PGC-1α signaling.
• LG improved redox balance by increasing the NAD+/NADH ratio and NQO1 activity.
• PH modulated cell cycle regulators and upregulated SIRT3 expression.
• The combination of LG and PH did not fully replicate the comprehensive effects of FPP, suggesting synergistic actions.

Conclusions:

• Fermented porcine placenta (FPP) acts as a multifactorial modulator of keratinocyte senescence.
• FPP exerts its anti-senescence effects through mitochondrial and redox-related mechanisms.
• The dipeptides LG and PH contribute distinctly to FPP's activity, highlighting the importance of multiple bioactive components in FPP for anti-aging benefits.