The link between oxidative stress and lifespan in Daphnia pulex

One of the major contributors to aging is the macromolecular damage leading to cell, tissue, and, ultimately, organ dysfunction. This process is an inevitable outcome of cellular biochemistry and is the origin of the diseases of older age. Intracellular reactive oxygen species (ROS) are products of the normal mitochondrial metabolism but are known to cause the most damage to macromolecules. It is believed that the mitochondrial DNA (mtDNA) is the primary target of the ROS generated by mitochondria. That is why the mutations in somatic mtDNA are linked with the process of normal aging in tissues such as skeletal muscle and neurons and a corresponding decline in the mitochondrial function with age.

There are naturally occurring variations in the mitochondrial genomes, leading to differences in the mitochondrial electron transport chain (ETC) efficiencies. These differences could result in less or more ROS and macromolecular damage and a change in the rate of aging. Mitochondrial (MT) complex I is a component of the ETC and a key source of ROS. The NADH dehydrogenase subunit 5 (ND5) is a conserved core protein of the subunits constituting the backbone of complex I.ND5 enables NADH dehydrogenase (ubiquinone) activity and is involved in mitochondrial electron transport. Ukhueduan et al. used Daphnia species as a model organism to explore the correlation between the naturally occurring sequence variations in ND5 and the lifespan.

Mutations in ND subunits disrupt either complex I assembly or enzyme activity and cause around 20% of isolated complex I deficiency cases. Mutations in the ND5 sequence are associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes in humans. Ukhueduan et al. identified naturally occurring ND5 sequence variations in ecologically distinct populations of the microcrustaceans Daphnia pulex and D. pulicaria. They examined its association with complex I enzyme activity and level of oxidative damage to total and mitochondrial proteins.

In this study, researchers examined the overall amount of oxidative damage to proteins, the activity levels of several ROS scavenger enzymes, and an associated ROS concentration level in young, middle-aged, and old organisms of closely related Daphnia with vastly different lifespans, RW20 or WF6 for short-lived and XVI-11 for long-lived. Previous studies have demonstrated that DNA and lipid damage from ROS are not likely involved as significant causative agents for aging. Thus, they examined oxidative damage in proteins.

WF6 and RW20 show more oxidative damage to proteins than XVI-11 at young and middle-ages, but the damage is similar in old organisms of both clones. The naturally occurring ND5 sequence variations observed in short-lived RW20 and WF6 correspond to reduced complex I activity and higher ROS generation. Thus, the short-lived clones generate more ROS, which corresponds well with higher amounts of oxidative damage to cytoplasmic and mitochondrial proteins. It led to the association of the natural variations in mitochondrial ND5 sequence to lower complex I activity and increased oxidative damage to proteins in Daphnia clones with shorter lifespans.

Although there is a corresponding increase in the activity of the ROS scavenging antioxidant mechanisms, the short-lived clones show an imbalance between ROS production and removal, thus accumulating damaged proteins and possibly contributing to their shorter lifespan. Oxidative stress, which has been shown to be a driver of lifespan and aging in other model organisms, also correlates similarly in Daphnia, a newer model system for research on aging. This study demonstrates that Daphnia is a perfect model system. It offers significant advantages with its unique reproduction type, availability of genome manipulation techniques, and naturally existing ecotypes with varied lifespans to understand natural determinants of lifespan. 

Source: link

‍