Research from China has found that blocking the enzyme asparagine endopeptidase (AEP) can extend the lifespan of aging mice by 17 percent, while also improving their memory, physical strength and metabolic health.
Age-related overactivity of AEP, also known as legumain, and its consequences in the body have been previously linked to health issues including Alzheimer's disease and DNA damage. The team decided to investigate whether blocking it could improve longevity and health in later life.
The study, published in iScience, used an AEP inhibitor called #11a mixed into the food of mice aged about 18 months. The treated mice lived an average of 28 months, compared with 24 months for the untreated control group. The researchers also observed fewer signs of age-related frailty in the treated group. The mice performed better on tests of exercise, strength and memory, and showed improved metabolic health, including better responses to insulin. Researchers also observed fewer signs of inflammation and cell aging in mice with inhibited AEP.
"Our findings support the idea that AEP is involved in multiple aging-associated pathological processes and that pharmacological inhibition of AEP may ameliorate several age-related phenotypes," the team wrote in their paper.
"In the current work, #11a alleviated multiple frailty indices in both male and female mice and was associated with attenuated age-related decline in physical and cognitive functions," the researchers wrote.
However, the study has limitations. It involved only a small group of mice, and there were variations in how much the mice ate; associated changes in calorie intake may explain some of the results. The next step is to figure out why inhibiting AEP has these effects. The study authors think overactive AEP may damage proteins that protect cells from wearing out, but more research is needed. Long-term safety also needs careful evaluation, as AEP has many useful jobs in the body. The mice did not show major adverse effects, but further study is required.
"Additional causal studies will be needed to determine the extent to which this pathway is required for the survival and health span phenotypes observed here," the team wrote.
Despite these caveats, the findings support further investigation into pharmacological AEP inhibition as a strategy to promote healthy aging.
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12 claims in this story checked against 1 source: 11 supported.
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- SupportedBlocking AEP extended the average lifespan of aging mice by 17%.ScienceAlert: “Untreated mice lived to an average age of 24 months, while #11a-treated mice averaged 28 months, four months longer. That translates to a 17 percent increase in lifespan.”
- Supported#11a-treated mice performed better on memory tests and seemed physically healthier.ScienceAlert: “the treated mice performed better on memory tests and seemed to be physically healthier, too.”
- Supported“Our findings support the idea that AEP is involved in multiple aging-associated pathological processes and that pharmacological inhibition of AEP may ameliorate several age-related phenotypes,” the team wrote.ScienceAlert: “"Our findings support the idea that AEP is involved in multiple aging-associated pathological processes and that pharmacological inhibition of AEP may ameliorate several age-related phenotypes," writes the team in their published paper.”
- Supported“In the current work, #11a alleviated multiple frailty indices in both male and female mice and was associated with attenuated age-related decline in physical and cognitive functions,” the researchers wrote.ScienceAlert: “"In the current work, #11a alleviated multiple frailty indices in both male and female mice and was associated with attenuated age-related decline in physical and cognitive functions," write the researchers.”
- Supported“Additional causal studies will be needed to determine the extent to which this pathway is required for the survival and health span phenotypes observed here,” the team wrote.ScienceAlert: “"Additional causal studies will be needed to determine the extent to which this pathway is required for the survival and health span phenotypes observed here," writes the team.”
- SupportedThe study used #11a mixed into the food of mice aged about 18 months.ScienceAlert: “The researchers put an AEP inhibitor called #11a in the food of some of the mice used in the experiments”
- SupportedThe treated mice lived an average of 28 months, compared with 24 months for untreated mice.ScienceAlert: “Untreated mice lived to an average age of 24 months, while #11a-treated mice averaged 28 months, four months longer.”
- SupportedThe treated mice showed fewer signs of frailty, did better in exercise, strength and memory tests, and had improved metabolic health, including better insulin responses.ScienceAlert: “The group given #11a showed fewer signs of age-related frailty, did better in exercise, strength, and memory tests, and showed improved metabolic health too (including better responses to insulin).”
- SupportedThe study involved only a small group of mice, and variations in food intake may explain some results through calorie-intake changes.ScienceAlert: “There were also some variations in how much the mice ate during the course of the study, and associated changes in calorie intake may explain some of the end results. The study involved only a small group of mice”
- SupportedThe mice did not show major adverse effects, but long-term safety needs careful evaluation because AEP has useful jobs in the body.ScienceAlert: “Then there's the issue of AEP having many useful and important jobs to do in the body. While the mice in this study didn't show any major adverse effects to the treatment, long-term safety will need to be carefully evaluated.”
- SupportedThe study authors think overactive AEP may damage proteins that protect cells from wearing out.ScienceAlert: “The study authors think overactive AEP may damage other proteins in the body that are there to protect cells from wearing out”
- Partly supportedThe findings support further investigation into pharmacological AEP inhibition as a healthy-aging strategy.ScienceAlert: “"These findings support further investigation of pharmacological AEP inhibition as a strategy to promote healthy aging," write the researchers.”
