Metformin improves cardiac stress tolerance and mitochondrial function during early aging.

Area of Science:

• Cardiovascular Biology
• Aging Research
• Mitochondrial Medicine

Background:

• Cardiac aging diminishes stress resilience, increasing susceptibility to myocardial injury.
• Elevated endoplasmic reticulum (ER) stress is a significant factor in cardiac aging, beginning in middle age.
• Metformin has previously shown benefits in late-aged hearts by reducing ER stress and enhancing mitochondrial function.

Purpose of the Study:

• To investigate the cardioprotective effects of metformin in early-aged hearts subjected to stress.
• To determine if metformin can mitigate ER stress and preserve mitochondrial function in the context of early cardiac aging and superimposed stress.

Main Methods:

• Eighteen-month-old mice, modeling early cardiac aging, were treated with metformin for two weeks prior to and during isoproterenol (ISO)-induced cardiac stress.
• Cardiac function and mitochondrial respiration were assessed after ISO exposure.
• Baseline and stress-induced ER stress levels were evaluated.

Main Results:

• Isoproterenol (ISO) impaired cardiac function and mitochondrial respiration in early-aged mice.
• Metformin treatment reduced baseline ER stress.
• Metformin significantly improved cardiac performance and mitochondrial function following ISO-induced stress.

Conclusions:

• Chronic metformin administration confers cardioprotection in early aging.
• Metformin attenuates ER stress and preserves mitochondrial function in aging hearts under stress.
• These findings highlight metformin's potential therapeutic role in mitigating age-related cardiac decline.