Does Cellular Metabolism from Primary Fibroblasts and Oxidative Stress in Blood Differ between Mammals and Birds? The (Lack-thereof) Scaling of Oxidative Stress

As part of mitonuclear communication, retrograde and anterograde signaling helps maintain homeostasis under basal conditions. Basal conditions, however, vary across phylogeny. At the cell-level, some mitonuclear retrograde responses can be quantified by measuring the constitutive components of oxidative stress, the balance between reactive oxygen species (ROS) and antioxidants. ROS are metabolic by-products produced by the mitochondria that can damage macromolecules by structurally altering proteins and inducing mutations in DNA, among other processes. To combat accumulating damage, organisms have evolved endogenous antioxidants and can consume exogenous antioxidants to sequester ROS before they cause cellular damage. ROS are also considered to be regulated through a retrograde signaling cascade from the mitochondria to the nucleus. These cellular pathways may have implications at the whole-animal level as well. For example, birds have higher basal metabolic rates, higher blood glucose concentration, and longer lifespans than similar sized mammals, however, the literature is divergent on whether oxidative stress is higher in birds compared with mammals. Herein, we collected literature values for whole-animal metabolism of birds and mammals. Then, we collected cellular metabolic rate data from primary fibroblast cells isolated from birds and mammals and we collected blood from a phylogenetically diverse group of birds and mammals housed at zoos and measured several parameters of oxidative stress. Additionally, we reviewed the literature on basal-level oxidative stress parameters between mammals and birds. We found that mass-specific metabolic rates were higher in birds compared with mammals. Our laboratory results suggest that cellular basal metabolism, total antioxidant capacity, circulating lipid damage, and catalase activity were significantly lower in birds compared with mammals. We found no body-size correlation on cellular metabolism or oxidative stress. We also found that most oxidative stress parameters significantly correlate with increasing age in mammals, but not in birds; and that correlations with reported maximum lifespans show different results compared with correlations with known aged birds. Our literature review revealed that basal levels of oxidative stress measurements for birds were rare, which made it difficult to draw conclusions.