We’ve long known that peptides offer targeted solutions for skin—from anti-ageing peptides that can help smooth the appearance of wrinkles to copper peptides for skin that boost collagen and specialised collagen peptides that help rebuild skin’s structural support. But what if combining specific peptides in skin care could unlock even greater rejuvenation?
New research reveals a breakthrough: specific peptide pairs (like Ac-PPYL + Pal-KTTKS) team up with niacinamide to:
Activate skin’s self-repair mode (via the NRF2 pathway)
Recharge cellular batteries (restoring ATP energy)
Work across all skin layers - addressing fine lines and deep support
It’s like giving your skin a coordinated renewal plan instead of random fixes. Even better? These proven, safe peptide combos mirror some of laser treatments’ rejuvenation magic – no downtime needed.
This research goes beyond the benefits of peptides we already love. It shows that the future of peptide skincare isn’t just about single ingredients—it’s about smart synergy for visible transformation.
COMBINATIONS OF PEPTIDES SYNERGISTICALLY ACTIVATE THE REGENERATIVE CAPACITY OF SKIN CELLS IN VITRO
Michael J. Flagler, Makio Tamura, Tim Laughlin, Scott Hartman, Julie Ashe, Rachel Adams, Kim Kozak, Kellen Cresswell, Lisa Mullins, Bradley B. Jarrold, Robert J. Isfort, Joseph D. Sherrill
BACKGROUND
Intrinsic and extrinsic skin ageing are both characterised by a progressive deterioration of the skin's youthful properties. These ageing-associated changes occur in all skin compartments, from the dermis to the epidermis. Consequently, a holistic approach to skin rejuvenation would ideally act across multiple skin layers.
OBJECTIVE
To explore the synergistic effects of peptides with distinct biological mechanisms of action on skin regeneration, particularly in combination with niacinamide, and to define optimal peptide combinations for skin rejuvenation.
METHOD
This study utilised microarray profiling to characterise the biological responses of peptide combinations, with or without niacinamide, in epidermal keratinocyte and dermal fibroblast cell lines.
Cellular functional assays were also conducted to confirm the synergistic effects observed.
The study further employed bioinformatics approaches to correlate the synergistic effects observed in gene expression to the transcriptomics of skin rejuvenation in response to fractional laser treatment.
RESULTS
Microarray analysis of skin cells treated with peptide combinations revealed synergistic changes in gene expression compared with individual peptide controls.
Notably, the combination of Ac-PPYL, Pal-KTTKS, and niacinamide synergistically activated the NRF2-mediated oxidative stress response in keratinocytes, a pathway vital for cellular defense against oxidative damage.
Furthermore, the combination of Ac-PPYL and Pal-KT synergistically restored cellular ATP levels depleted by reactive oxygen species (ROS), highlighting the potential of these combinations in promoting skin repair.
CONCLUSION
This study identified novel in vitro skin repair mechanisms beyond the previously known functions of individual peptides, correlating these findings to the transcriptomics of the skin's rejuvenation response to fractional laser treatment.
These results suggest that specific peptides, when combined appropriately, can act synergistically to enhance the regenerative capacity of skin cells, offering a potential non-invasive approach to skin rejuvenation.
Conflict of interest:
M.J.F., M.T., T.L., S.H., J.A., K.K. K.C., L.M., B.B.J., R.J.I. and J.D.S. are full-time employees of The Procter & Gamble Company.