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Despite longstanding scientific interest in the centrality of mitochondria to biological aging, directly controlling mitochondrial function to test causality has eluded researchers. We show that specifically boosting mitochondrial membrane potential through a light-activated proton pump reversed age-associated phenotypes and extended C. elegans lifespan. We show that harnessing the energy of light to experimentally increase mitochondrial membrane potential during adulthood alone is sufficient to slow the rate of aging.

Hydrogen peroxide (H2O2) functions as a second messenger to signal metabolic distress through highly compartmentalized production in mitochondria. The dynamics of ROS generation and diffusion between mitochondrial compartments and into the cytosol govern oxidative stress responses and pathology, though our understanding of these processes remains limited. Here, we couple the H2O2biosensor, HyPer7, with optogenetic stimulation of the ROS-generating protein KillerRed targeted into multiple mitochondrial microdomains. Single mitochondrial photogeneration of H2O2demonstrates the spatiotemporal dynamics of ROS diffusion and transient hyperfusion of mitochondria due to ROS. Measurement of microdomain-specific H2O2diffusion kinetics reveals directionally selective diffusion through mitochondrial microdomains. All-optical generation and detection of physiologically-relevant concentrations of H2O2between mitochondrial compartments provide a map of mitochondrial H2O2diffusion dynamicsin situ. These kinetic details of spatiotemporal ROS dynamics and inter-mitochondrial spreading forms a framework to understand the role of ROS in health and disease.

Recent studies demonstrated that alcohol consumption can induce epigenetic changes in the brain, although the exact mechanism underlying such changes remained unclear. Now, a report by Mews et al. shows a direct link between alcohol consumption and histone acetylation changes in the brain, which are mediated by the neuronal acetyl-CoA synthase, ACSS2.

Regulated metabolic activity is essential for the normal functioning of living cells. Indeed, altered metabolic activity is causally linked with the progression of cancer, diabetes, neurodegeneration, and aging to name a few. For instance, changes in mitochondrial activity, the cell's metabolic powerhouse, have been characterized in many such diseases. Generally, the oxygen consumption rates of mitochondria were considered a reliable readout of mitochondrial activity and measurements in some of these studies were based on isolated mitochondria or cells. However, such conditions may not represent the complexity of a whole tissue. Recently, we have developed a novel method that enables the dynamic measurement of oxygen consumption rates from whole isolated fly heads. By utilizing this method, we have recorded lower oxygen consumption rates of the whole head segment in young versus aged flies. Secondly, we have discovered that lysine deacetylase inhibitors rapidly alter the oxygen consumption in the whole head. Our novel technique may therefore aid in uncovering new properties of various drugs, which may impact metabolic rates. Furthermore, our method may give a better understanding of metabolic behavior in an experimental setup that more closely resembles physiological states.