Garlic-derived compounds may extend lifespan and improve healthy aging by improving metabolism.
Hydrogen sulfide is a small signaling molecule that the body produces using sulfur-containing compounds. It helps cells respond to stress, generate energy, and regulate how proteins function. Researchers wanted to know whether maintaining higher levels of this molecule over time could slow aging in mammals.
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The study included a long-term lifespan experiment in healthy male mice starting at 20 weeks of age and continuing until natural death. Their diet was supplemented with a garlic-derived mixture of diallyl sulfur compounds (molecules with a sulfur center and two small carbon "arms" attached to it). To isolate the role of individual components, separate 18-week experiments tested two purified compounds, diallyl disulfide (DAD) and diallyl trisulfide (DAT), under both the standard and a high-fat diet. The researchers also measured plasma protein persulfidation (a hydrogen sulfide–dependent modification that can change how proteins function) in blood samples from 288 adults with multiple chronic health conditions.
- In the mice, a single oral dose of the garlic-derived diallyl sulfur mixture briefly increased the blood's capacity to generate hydrogen sulfide.
- Median survival increased from 787 days in untreated mice to 877 days in those receiving the garlic-derived compounds.
- Treated mice also performed better on tests of grip strength, hanging endurance, coordination, and several forms of memory later in life.
- DAD and DAT improved insulin sensitivity and physical performance under both diets, with DAD showing stronger improvements in blood sugar control after a glucose drink among mice on a high-fat diet.
- DAD and DAT shifted liver fat toward smaller droplets compared with untreated mice under both diets, with the clearest difference seen under the high-fat diet, which is known to cause unusually large fat deposits in the liver.
- At the molecular level, the treatments were linked to reduced activity in inflammation-related pathways, lower mTOR signaling (a central metabolic control pathway), and increased protein persulfidation in the liver.
- In humans, higher plasma protein persulfidation was linked to stronger grip strength and lower triglyceride levels.
In the liver, storing fat in smaller droplets makes it easier to access and use, whereas large fat droplets tend to build up and interfere with normal metabolism, which can contribute to metablic stress and poorer blood sugar control over time. Consistent with this shift, the liver showed lower activity in inflammation-related pathways and reduced mTOR signaling, which promotes cell growth and energy storage in nutrient-rich conditions but is often downregulated in longer-lived, metabolically healthier states. The increase in protein persulfidation offers a possible explanation for these changes, as it can directly alter how proteins involved in metabolism and stress responses function.
The study has important limitations. Results from animal studies cannot be directly translated to humans, and the human data only showed a few associations, which do not prove that these compounds caused the observed health differences. Even so, if controlled clinical trials confirm similar effects in people, these findings could point to a role for sulfur-containing compounds in supporting metabolic health and healthy aging. To learn more about how garlic affects metabolism, see Q&A #78, where I explore its effects on cholesterol levels.