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" "Like rapamycin, metformin mimics aspects of calorie restriction. But instead of inhibiting TOR, it limits the metabolic reactions in mitochondria, slowing down the process by which our cellular powerhouses convert macronutrients into energy.20 The result is the activation of AMPK, an enzyme known for its ability to respond to low energy levels and restore the function of mitochondria. It also activates SIRT1, one of my lab's favorite proteins. Among other beneficial effects, metformin inhibits cancer cell metabolism, increases mitochondrial activity, and removes misfolded proteins.21
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Trading reproduction for repair, the sirtuins order our bodies to "buckle down" in times of stress and protect us against the major diseases of aging: diabetes and heart disease, Alzheimer's disease and osteoporosis, even cancer. They mute the chronic, overactive inflammation that drives diseases such as atherosclerosis, metabolic disorders, ulcerative colitis, arthritis, and asthma. They prevent cell death and boost mitochondria, the power packs of the cell. They go to battle with muscle wasting, osteoporosis, and macular degeneration. In studies on mice, activating the sirtuins can improve DNA repair, boost memory, increase exercise endurance, and help the mice stay thin, regardless of what they eat. These are not wild guesses as to their power; scientists have established all of this in peer-reviewed studies published in journals such as Nature, Cell, and Science.
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But the true extent to which the survival circuit is conserved between yeast and humans wasn't fully known until 2017, when Eva Bober's team at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, Germany, reported that sirtuins stabilize human rDNA.23 Then, in 2018, Katrin Chua at Stanford University found that, by stabilizing human rDNA, sirtuins prevent cellular senescence — essentially the same antiaging function as we had found for sirtuins in yeast twenty years earlier.24