Testing hypotheses of aging in long-lived mice of the genus Peromyscus: association between longevity and mitochondrial stress resistance, ROS detoxification pathways, and DNA repair efficiency

Abstract

In the present review we discuss the potential use of two long-lived mice of the genus Peromyscus—the white-footed mouse (P. leucopus) and the deer mouse (P. maniculatus) maximum lifespan potential ∼8 years for both—to test predictions of theories about aging from the oxidative stress theory, mitochondrial theory and inflammatory theory. Previous studies have shown that P. leucopus cells exhibit superior antioxidant defense mechanisms and lower cellular production of reactive oxygen species (ROS) than do cells of the house mouse, Mus musculus (maximum lifespan ∼3.5 years). We present new data showing that mitochondria in P. leucopus cells produce substantially less ROS than mitochondria in M. musculus cells, and that P. leucopus mitochondria exhibit superior stress resistance to those of M. musculus. We also provide evidence that components of the DNA repair system (e.g., pathways involved in repair of DNA damage induced by γ-irradiation) are likely to be more efficient in P. leucopus than in M. musculus. We propose that mitochondrial stress resistance, ROS detoxification pathways and more efficient DNA repair contribute to the previously documented resistance of P. leucopus cells toward oxidative stress-induced apoptosis. The link between these three pathways and species longevity is discussed.