Fucoxanthin, a bioactive compound derived from edible seaweed, supports proteostasis and protects against stress and senescence.

Abstract

Emerging evidence supports the maintenance of cellular proteostasis as a key process in resisting age-related diseases. Its intervention by natural compounds is expected to benefit the healthcare system. In the current study, we recruited a unique amyloid beta (Aβ) aggregation-based in vitro screening system and identified fucoxanthin (Fx) as a candidate compound possessing protein de-aggregation potential. Phenotypic and molecular analyses revealed that Fx mitigated endoplasmic reticulum and heat stress by modulating the cellular unfolded protein response and heat shock response, respectively. Furthermore, Fx alleviated senescence-associated markers and restored proteostasis by rescuing chaperone expression and proteasome activity in human senescent fibroblasts. The above protective effect of Fx was further validated in human induced pluripotent stem cells (hiPSC)-derived neurons and Aβ-GFP transgenic Caenorhabditis elegans (C. elegans). Altogether, our results demonstrate the proteostasis-promoting potential of Fx that may be useful for managing degenerative diseases and promoting healthy aging.