Starfish Extracts Activate Mitophagy and Reverse Skin Cell Aging Markers

Skin aging is driven in part by the accumulation of dysfunctional mitochondria in dermal fibroblasts, which generates oxidative stress, promotes inflammatory secretion, and locks cells in a senescent state. Mitophagy—the selective autophagy of damaged mitochondria—is a critical quality-control mechanism that declines with age, making its activation an appealing anti-aging target. This study explored whether extracts from two Pacific starfish species could activate mitophagy and reverse senescence phenotypes in human dermal fibroblasts (HDFs).

The research team established both non-senescent and replicatively senescent HDF models, confirmed by SA-β-galactosidase staining and elevated mitochondrial ROS. Cytotoxicity testing showed that doses below 50 µg/mL were safe over 72 hours. Cells were treated with Asterias pectinifera (Ap) or Asterias amurensis (Aa) extracts, with resveratrol as a positive control. Both extracts reduced the proportion of SA-β-gal-positive cells by more than 20%, lowered p21 mRNA, and modulated Bax/Bcl-2 expression. Multiplex Luminex and ELISA assays confirmed significant reductions in secreted IL-6, IL-8, and MMP-1. ERK phosphorylation and NF-κB transcriptional activity were also suppressed, pointing to broad anti-inflammatory signaling.

Mitophagy was assessed using multiple complementary approaches: transmission electron microscopy visualized autophagosome accumulation containing fragmented mitochondria; MitoTracker/LysoTracker co-staining showed enhanced mitochondrial-lysosomal colocalization; and HDFs stably expressing mitochondria-targeted Keima (mtKeima) provided quantitative flow cytometric measurement, revealing an approximately two-fold increase in mitophagy with Ap or Aa treatment—comparable to the positive control CCCP. Degradation of COX II, a mitochondrial inner membrane protein, further confirmed mitophagic flux. Results were replicated in HeLa-mtKeima cells.

Crucially, siRNA-mediated knockdown of PINK1 abolished the mitophagy-inducing effects of both extracts and reversed their suppression of MMP-1 and p21, demonstrating that the anti-senescence activity is mechanistically dependent on the PINK1/Parkin pathway. Separately, Ap and Aa treatment significantly reduced mitochondrial ROS accumulation and improved both basal and maximal oxygen consumption rates in senescent HDFs, indicating functional mitochondrial restoration.

These findings position starfish-derived extracts as biologically active agents capable of engaging a specific, well-validated longevity pathway. The study is limited to in vitro cell models and does not yet establish active compound identity, bioavailability, or clinical efficacy, but it lays a mechanistic foundation for developing novel cosmeceuticals targeting mitochondrial aging in skin.