Mitochondria are organelles that participate in a variety of cellular processes, including lipid degradation and carbohydrate metabolism. Additionally, they are responsible for meeting the energetic requirements of tissues via cellular respiration. When mitochondria fail to carry out these functions properly, mitochondrial dysfunction occurs.
Mitochondrial dysfunction plays a role in the development of type-2 diabetes, a chronic inflammatory disease characterised by hyperglycemia and hyperinsulinemia. One substance used to treat it is metformin, an anti-diabetic drug that can regulate the amount of blood glucose.
The researchers analysed the anthropometric (body size, weight, and stature) and biochemical markers of 135 healthy individuals and 120 type-2 diabetes patients recruited at Valencia’s University Hospital Dr Peset’s Endocrinology Department. Among these, 81 patients were receiving metformin treatment and 39 were not.
The study demonstrates an improvement in mitochondrial function in type-2 diabetes patients receiving metformin. Additionally, researchers observed a reduction in the interactions between leukocytes and endothelial cells in these patients, implying a reduction in the inflammatory process associated with type-2 diabetes.
Apart from type-2 diabetes, other diseases may be caused by mitochondrial dysfunction. Numerous studies indicate that arteriosclerosis, a condition characterised by the narrowing of arteries, may also be associated with impaired mitochondrial function. Thus, metformin may also be an effective treatment for the development of arteriosclerosis and, as a result, cardiovascular diseases, according to this study.
Another study’s findings suggest that metformin’s healthspan benefits outside of diabetes are limited by aging.
Furthermore, a life-prolonging effect of metformin has recently been shown in mice, flies, and worms.
The team examined the metabolic response of young and old non-diabetic organisms to metformin treatment using the nematode C. elegans and human primary cells in the study.
Type 2 diabetes is an aging disease, and many patients begin treatment with metformin at an advanced age.
On the basis of improved survival and decreased prevalence of aging-associated diseases in diabetes patients receiving metformin, it was proposed that metformin’s longevity benefits could be extended to metabolically healthy older adults.
They were able to identify significant limitations to metformin’s use as a longevity medication.
In contrast to the beneficial effects of metformin on young organisms, metformin consumption at an older age shortens lifespan.
The researchers discovered that the same metformin treatment that prolonged life in young C. elegans worms was highly toxic in elderly animals.
Up to 80 percent of the elderly population treated with metformin died within the first 24 hours of treatment.
Consistently, as human primary cells approached replicative senescence, they demonstrated a progressive decrease in metformin tolerance.
The researchers were able to connect this finding to older cells and nematodes’ decreased ability to adapt to metabolic stressors such as metformin.
They suggest that the same dose of the drug that increased the longevity of young organisms was toxic at old age.
This study establishes a link between the reversal of metformin benefits in late life and a decline in key metabolic activities in elderly animals, elucidating the unique mechanism underlying metformin’s age-specific adverse effects.
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