S1PC (a garlic-derived metabolite) activates LKB1 through enhanced tertiary complex formation, promotes eNAMPT secretion from white adipose tissue targeting the hypothalamus, and improves skeletal muscle force and frailty indices in aged mice while also increasing circulating eNAMPT in healthy humans.
Key Findings
Results
S1PC activates LKB1 by enhancing its tertiary complex formation with STRAD and MO25.
S-1-propenyl-L-cysteine (S1PC) is a bioactive compound derived from garlic (Allium sativum L.) and its aged extract.
The mechanism involves enhanced formation of the LKB1-STRAD-MO25 tertiary complex.
LKB1 (liver kinase B1) activation by S1PC was identified as the upstream molecular mechanism driving downstream signaling effects.
This represents a previously unknown mechanism of S1PC molecular action.
Results
S1PC stimulates phosphorylation of SIRT1 downstream of LKB1 activation.
SIRT1 is described as a mammalian NAD+-dependent protein deacetylase.
S1PC activates the LKB1-SIRT1 pathway specifically.
Phosphorylation of SIRT1 occurs as a consequence of LKB1 activation by S1PC.
The LKB1-SIRT1 axis was identified as the key signaling pathway mediating S1PC's downstream effects in white adipose tissue.
Results
S1PC promotes the secretion of extracellular NAMPT (eNAMPT) from white adipose tissue (WAT).
eNAMPT stands for extracellular nicotinamide phosphoribosyltransferase.
The effect on eNAMPT secretion is mediated through the LKB1-SIRT1 pathway in WAT.
White adipose tissue is the specific tissue where S1PC exerts this secretory effect.
The promotion of eNAMPT secretion from WAT is a central mechanistic finding linking S1PC to systemic effects.
Results
eNAMPT secreted from WAT specifically targets the hypothalamus to enhance skeletal muscle function.
eNAMPT from WAT was found to specifically target the hypothalamus rather than acting directly on muscle.
This hypothalamic signaling pathway mediates the downstream effects on skeletal muscle.
The mechanism involves a WAT-to-hypothalamus-to-muscle signaling axis.
This tissue-specific targeting of the hypothalamus by WAT-derived eNAMPT was identified as a key feature of the pathway.
Results
S1PC treatment significantly enhances skeletal muscle force and improves frailty indices in aged mice.
Experiments were conducted in aged mice as a model of muscle aging and frailty.
Both skeletal muscle force and frailty indices showed significant improvement with S1PC treatment.
The improvements in muscle function were attributed to the WAT eNAMPT-hypothalamic signaling axis stimulated by S1PC.
These findings suggest S1PC counteracts skeletal muscle aging.
Results
S1PC increases circulating eNAMPT levels in human individuals who maintain healthy adipose mass.
The effect of S1PC on circulating eNAMPT was evaluated in human subjects.
The increase in circulating eNAMPT was observed specifically in individuals with healthy adipose mass.
This finding translates the mouse mechanistic data to a human context.
The dependency on healthy adipose mass suggests WAT quantity or quality may modulate the response to S1PC in humans.
What This Means
This research suggests that a compound found in garlic called S-1-propenyl-L-cysteine (S1PC) works through a specific chain of molecular events to help counteract muscle aging. S1PC activates a protein called LKB1 in fat tissue by helping it form a stable complex with two partner proteins. This activated LKB1 then triggers another protein (SIRT1), which ultimately causes fat cells to release a signaling molecule called eNAMPT into the bloodstream. Remarkably, this released eNAMPT travels specifically to the hypothalamus in the brain, which then sends signals that improve muscle strength and reduce signs of frailty in aged mice.
The study also tested this effect in humans and found that people who consumed S1PC and had healthy amounts of body fat showed increased levels of circulating eNAMPT, suggesting the same biological pathway may be active in people. This is significant because it links a dietary compound from garlic to a concrete molecular pathway — from fat tissue to the brain to muscles — that may help preserve physical function as people age.
This research suggests that garlic-derived compounds, particularly S1PC found in aged garlic extract, may support muscle health in older individuals by stimulating fat tissue to send beneficial signals to the brain. The finding that the effect depends on maintaining healthy adipose (fat) tissue also points to the importance of body composition in older adults for this pathway to function effectively. Further clinical studies would be needed to determine appropriate doses and confirm these benefits in larger human populations.
Suzuki J, Yoshioka K, Kurita M, Sugimoto T, Eguchi T, Ito N, et al.. (2026). Garlic-derived metabolite activates LKB1, promotes adipose eNAMPT secretion, and improves age-related muscle function via hypothalamic signaling.. Cell metabolism. https://doi.org/10.1016/j.cmet.2026.04.006