Metformin is a common type 2 diabetes drug.
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 a new study, 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 research was done by a team at the Leibniz Institute on Aging and elsewhere.
While people today are getting older and older, diseases that are associated with age (e.g. cardiovascular diseases, cancer, dementia, and diabetes) are also increasing.
Reaching late-life while staying healthy is of high priority.
Recently, the drug metformin, which has been used for decades to treat patients suffering from type 2 diabetes, was linked to the reduced risk of cancer development and showed the potential to alleviate heart diseases in humans.
Furthermore, a life-prolonging effect of metformin has recently been shown in mice, flies, and worms.
So, does this make metformin the new miracle drug to prolong life and even delay aging-associated diseases?
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.
Metformin affects blood glucose levels by increasing the effect of the body’s own insulin, and it is currently the most frequently prescribed drug for diabetes type 2.
Type 2 diabetes is an aging-related disease, and many patients begin metformin treatment at an advanced age.
Based on the increased survival and reduced prevalence of aging-associated diseases in diabetes patients under metformin treatment, it was proposed that the longevity benefits of metformin could be extended to metabolically healthy older people.
They were able to uncover important limitations for the use of metformin as longevity medicine.
In contrast to the positive longevity effects in young organisms that received metformin, lifespan is shortened through metformin intake at an older age.
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 were able to 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.
One author of the study is Dr. Maria Ermolaeva.
The study is published in the journal Nature Metabolism.
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