Mitoflash Is An Early Predictor Of Lifespan In C. Elegans

Aging is a gradual and systemic functional decline of an organism sometime after reproduction begins. Genetic, environmental, and stochastic factors all influence aging and determine how long animals eventually live. Mitochondria are pivotal to bioenergetics, free radical metabolism, and cell death. Not surprisingly, mitochondria take a central position in several prominent aging theories, e.g. the rate of living theory, the free radical theory, and the mitochondrial theory of aging. To better understand the physiology of mitochondria during the process of aging in C. elegans, and in the hope of identifying an early biomarker of aging, we used in vivo fluorescence imaging to characterize a physiological phenomenon directly related to superoxide production inside mitochondria. This phenomenon, called mitochondrial superoxide flash or mitoflash, is an intermittent, quantal mitochondrial activity that is linked to energy metabolism and free radical production. The mitoflash production requires the integrity of the mitochondrial electron transport chain (ETC), and the mitoflash frequency is highly sensitive to the metabolic status of the cell and a variety of insults including oxidative stress. Thus, mitoflash serves as a frequency-coded biological oscillator reflecting mitochondrial function in intact cells and even in live animals.We have found that mitoflash can serve as a novel predictor of lifespan in C. elegans. By in vivo imaging of the pharyngeal-muscle mitoflash events during the lifetime of C. elegans, we found that the mitoflash activity in wild-type (WT) animals was highly sensitive to changes in metabolic states and oxidative stress, and displayed a robust early peak on adult day2-3and a later one on day8.5-9.5. Surprisingly, genetic mutations in diverse signaling pathways inversely modified lifespan and the mitoflash activity on adult day3. Furthermore, the day-3mitoflash activity also negatively correlated with the lifespan of individual WT worms whose lifespan variations are presumably due to epigenetic fluctuations. Drug treatment that shortened lifespan tended to enhance the day-3mitoflash. This is the first time that an early biomarker has been found that can predict the average lifespans of different mutants of the same species, and the lifespans of individual animals from an isogenic population in the same environment. That day-3mitoflash frequency is a predictor of C. elegans lifespan supports the notion that the rate of aging, although adjustable in later life, has been set to a considerable degree before reproduction ceases.