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Researchers found a sulfur-based molecule derived from aged garlic activated a fat-to-brain signaling pathway tied to muscle performance and cellular energy regulation in mice and middle-aged adults.
By yourNEWS Media Newsroom
Scientists investigating compounds found in aged garlic extract have identified a biological pathway that may influence muscle performance and age-related physical decline through interactions between fat tissue, the brain, and the nervous system.
The findings, published in Cell Metabolism, centered on S-1-propenyl-L-cysteine, or S1PC, a sulfur-containing molecule naturally present in aged garlic preparations. Researchers from Washington University and research institutions in Japan reported that the compound stimulated production of a protein associated with cellular energy maintenance and improved physical performance markers in older laboratory mice.
In the animal portion of the study, mice receiving daily doses of S1PC over an eight-month period demonstrated stronger muscle contractions, improved grip strength, lower frailty scores, and body temperatures that more closely resembled those of younger animals.
Researchers also conducted a placebo-controlled human trial involving healthy adults between the ages of 20 and 49. Participants over age 40 with healthy levels of body fat experienced increased blood concentrations of extracellular nicotinamide phosphoribosyltransferase, known as eNAMPT, after receiving a single dose of S1PC.
The study focused on the relationship between eNAMPT and NAD+, a molecule essential for cellular energy production that declines with age. Scientists have previously linked reduced NAD+ levels to aging-related changes in metabolism and tissue function.
According to the researchers, S1PC enters white adipose tissue shortly after absorption and activates a protein called LKB1 inside fat cells. This process stimulates release of eNAMPT into circulation.
Rather than moving directly into muscle tissue, the protein appears to travel to the hypothalamus, an area of the brain responsible for regulating metabolism, temperature, and autonomic nervous system activity. Researchers reported that the hypothalamus then relays signals through the nervous system to skeletal muscles, resulting in improved muscle performance.
The study identified this fat-to-brain-to-muscle communication route as distinct from more commonly studied cellular energy pathways involving AMPK, a regulator frequently associated with exercise and metabolism.
Garlic has been extensively studied for its biological activity, including potential effects on cardiovascular function, inflammation, and blood pressure regulation. Researchers noted that garlic contains multiple sulfur-based compounds formed from S-alk(en)yl-L-cysteine sulfoxides, which are converted into bioactive molecules during processing and aging.
In the mouse experiments, researchers began treatment at an age corresponding to later middle age in humans. Muscle improvements were measured through electrical stimulation testing and grip strength analysis.
Although muscle performance improved, scientists reported no measurable increase in muscle mass, suggesting the compound enhanced function rather than stimulating muscle growth.
To determine whether the nervous system played a direct role, researchers administered a nerve-blocking drug before treatment with S1PC. Under those conditions, the muscle-related benefits disappeared.
Scientists also examined genetically modified mice lacking fat-derived eNAMPT. Those animals displayed significantly weaker muscle force, further supporting the importance of the signaling pathway identified in the study.
The human trial included 44 healthy Japanese adults who received either a placebo or concentrated garlic powder standardized to contain 17% S1PC. After participant withdrawals, 19 remained in the treatment group and 21 in the placebo group.
Researchers measured blood markers after administration and found elevated eNAMPT levels 120 minutes after dosing among participants aged 40 and older who maintained healthy body fat levels. No comparable increase was observed in the placebo group.
Participants categorized as underweight did not exhibit the same response, suggesting the mechanism may depend on the presence of sufficient adipose tissue.
Investigators also reported that S1PC did not stimulate fat breakdown, indicating the compound acted through targeted molecular signaling rather than broad metabolic disruption.
The researchers said several questions remain unresolved, including which specific hypothalamic neurons respond to eNAMPT signaling, whether responses differ between males and females, and whether prolonged supplementation could improve muscle function in humans over time.
Because the human trial measured only short-term blood marker changes after a single dose, the study did not evaluate long-term effects on strength, mobility, or frailty in people.
The authors concluded that additional clinical trials will be necessary to determine whether the signaling pathway observed in mice can produce sustained functional benefits in aging human populations.
Source: Natural News
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