In a recent study at the Leibniz Institute on Aging and elsewhere, researchers found that age is decisive for the positive or negative effects of the diabetes drug metformin.
These findings suggest that aging sets a limit for the healthspan benefits of metformin outside of diabetes.
The study is published in the journal Nature Metabolism. One author is Dr. Maria Ermolaeva.
While people today are getting older and older, diseases that are linked to age (e.g. cardiovascular diseases, cancer, dementia, and diabetes) are also increasing.
Reaching late-life while staying healthy is of high priority.
Metformin is a common type 2 diabetes drug. But recently, it was found to extend the life span of young non-diabetic animals but the responses of older organisms to metformin remain unexplored.
In addition, the drug was linked to the reduced risk of cancer development and showed the potential to alleviate heart diseases in humans.
In the study, the team used the nematode C. elegans and human primary cells to examine the metabolic response of young and old non-diabetic organisms to metformin treatment.
The team found that the very same metformin treatment that prolonged life when C. elegans worms were treated at a young age, was highly toxic when animals of old age were treated.
Up to 80% of the population treated at old age were killed by metformin within the first 24 hours of treatment.
Consistently, human primary cells demonstrated a progressive decrease in metformin tolerance as they approached replicative senescence.
The researchers link this finding to the reduced ability of old cells and old nematodes to adapt to metabolic stressors like metformin.
They suggest the exact the same dose of the drug that increased longevity of young-treated organisms was harmful in animals treated at old age.
This work links the reversal of metformin benefits in late life to a decline of key metabolic activities in old animals, describing the unique mechanism of the age-specific adverse effects of metformin.
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