20(S)-ginsenoside Rg3, a compound derived from ginseng, extended lifespan in C. elegans while preserving locomotion, pharyngeal pumping, and neuronal integrity. The mechanism involves remodeling of phosphoinositide lipids at lysosomal membranes, suppression of TORC1 signaling, and nuclear activation of HLH-30/TFEB, which together restored autophagic flux and lysosomal function in aged neurons. Rg3 also reduced polyglutamine aggregation and protected dopaminergic neurons from α-synuclein-induced degeneration.
Key Points
- Rg3 extended C. elegans lifespan and preserved locomotion and feeding
- Lysosomal lipid remodeling suppressed TORC1 and activated HLH-30/TFEB
- Compound protected dopaminergic neurons from α-synuclein-driven degeneration
Longevity Analysis
Lysosomal decline sits upstream of much of what we recognize as neurological aging: when the cell's disposal machinery slows, misfolded protein accumulates and neurons lose function long before they die. Targeting the lipid composition of lysosomal membranes represents a more precise entry point than broad nutrient-sensing inhibition, and the TORC1–TFEB axis engaged here is conserved well beyond the nematode. The practical implication is that clearance capacity — the body's internal waste management — is modifiable late in life, and that supporting it may matter more for cognitive durability than adding further inputs.
Original published by Wiley Aging Cell, by Haiyang Yu, Shiming Li, Yongsheng Chen, Yaoyong Zeng, Junbu Li, Yuxin Guo, Wanxiang Zhang, Lizhu Zhang, Longnong You, Kuncan Chen, Jinhong Wu, Dan Gan, Jiane‐Kang Liu, Lingjun Zheng .