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

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

Losing One’s Temper: Contingency in Early Modern Medicine

How scientific knowledge relates to medical practice is not always straightforward. On the one hand, natural philosophers deal with the universal, with what is true regardless of all circumstances; on the other hand, physicians struggle with the immediate and pressing needs of the individual patient. Yet, in Galenic medicine there were three ways of dealing with various forms of life: the notion of temperament, a fluid understanding of disease, and a rigid method of semiotics. These three fields were interconnected; the contingencies of one were the foundations of another. Together, they bridged the gap between the universe and the patient, taming the four primary qualities of the material world for use in medical practice. Indeed, they also took on a moral dimension, providing rules of conduct to help physicians face the unknown. So when Galenic medicine fell in the seventeenth century, the delicate union between knowledge and practice fell with it. Through the works of William Harvey (1578-1657), Richard Lower (1631-1691) and John Locke (1632-1704), this chapter examines how each one of these Galenic connections was questioned and replaced with an understanding consistent with the new experimental philosophy. However, as the works of Friedrich Hoffman (1660-1742) illustrate, this did not create a more rational medicine – in fact, the opposite. More rigorous philosophical standards only led to a proliferation of sometimes contradictory medical theories; the practicing physician left with no means to decide between them. Contingency was still central to medicine but hidden from view