Mitochondria are pivotal to bioenergetics, free radical metabolism and cell death. Mitochondria take a central position in many prominent aging theories. 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 mitoflash, is an intermittent, quantal mitochondrial activity that is linked to energy metabolism and free radical production. We have found that mitoflash can serve as a novel predictor of lifespan in C.elegans. The mitoflash activity in wild-type animals was highly sensitive to changes in metabolic states and oxidative stress, and displayed a robust early peak on adult day 3 and a later one on day 9. Surprisingly, genetic mutations in diverse signaling pathways inversely modified lifespan and the mitoflash activity on adult day 3 (R2³ 0.40, p<0.001, cubic spline or linear regression; Spearman's correlation=-0.65). Drug treatments that extended (or shortened) lifespan tended to reduce (or enhance) the day-3 mitoflash (R2³ 0.40, p< 0.005, cubic spline or linear regression; Spearman's correlation=-0.64). Furthermore, the day-3 mitoflash activity also negatively correlated with the lifespan of individual wildtype worms (R2=0.28, p<0.001, linear regression).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, the average population lifespans of animals of the same genetic makeup but under different environmental conditions, and lifespans of individual animals from an isogenic population in the same environment. The unexpected power of mitoflash as an early lifespan predictor suggests that the mitochondrial status, metabolic or oxidative or both, is intimately linked to the process of aging.

Authors: Shen, Enzhi, Song, Chunqing, Lin, Yuan, Zhang, Wenhong, Su, Peifang, Liu, Wenyuan, Zhang, Pan, Xu, Jiejia, Lin, Na, Zhan, Cheng, Wang, Xianhua, Shyr, Yu, Cheng, Heping, Dong, Mengqiu

Affiliations:
- Peking University, Beijing, China
- China Agricultural University, Beijing, China
- Vanderbilt Center for Quantitative Sciences, Vanderbilt University, Nashville, USA
- National Institute of Biological Sciences, Beijing, China