The open access paper here presents an interesting result in mitochondrial biology. Mitochondria are the power plants of the cell, a herd of bacteria-like structures responsible for packaging chemical energy store molecules. They have their own small genome of a few mitochondrial genes. A mitochondrion may have one or several copies of this genome, and mitochondria promiscuously fuse together, divide, and swap around their component parts from one to another. This makes it quite hard to understand how their age-related dysfunction and damage progresses in detail.
Nonetheless, it is well demonstrated that mitochondria become progressively less functional with advancing age, and this is particularly relevant in energy-hungry tissues such as muscles and the brain. Some of this decline may be reaction to forms of cell and tissue damage, and some of this is due to stochastic mutational damage occurring to mitochondrial DNA. In this context, the researchers here show that forcing an increase in the number of copies of mitochondrial DNA can maintain mitochondrial function in old age, and thereby slow vascular aging. It remains unclear, however, as to the exact chain of mechanisms that make this the case: the causes and immediate consequences of an age-related reduction in the number of copies of mitochondrial DNA are not well understood at this point in time.
Mitochondria contain multiple copies of mitochondrial DNA (mtDNA) that encode ribosomal and transfer RNAs and many essential proteins required for oxidative phosphorylation. Loss of mtDNA integrity by both altered mitochondrial DNA copy number (mtCN) and increased mutations is implicated in cellular dysfunction with aging. Reactive oxygen species (ROS), many of which are generated by mitochondria, also increase with age. However, the role of mitochondria in aging may extend beyond ROS, and it is unclear whether decreased mitochondrial function promotes vascular aging directly or is just a consequence of aging.
Aging of the large conduit arteries is a major cause of morbidity and mortality, contributing to hypertension (high blood pressure) and stroke. Currently, it is unclear what the earliest time points that constitute vascular aging in laboratory mice are, which physiological measures of large artery stiffness correspond most closely to humans, and whether similar processes underlie changes in mechanical properties in mouse and human arteries. Aging research is time-consuming and expensive because of the long time courses needed. Therefore, identifying the earliest time points that show the most sensitive and reproducible changes and parameters is crucial in obtaining scientific consensus for mouse models of vascular aging.
We examined multiple parameters of vascular function, histological markers, and markers of mitochondrial damage and function during normal vascular aging, and the effects of reducing or augmenting mitochondrial function on the onset and progression of vascular aging. We identify early, standardized time points and reproducible physiological parameters for vascular aging studies in mice. Vascular aging begins at far earlier time points than previously described in mice, with compliance, distensibility, stiffness, and pulse wave velocity (PWV) being the best discriminators for normal aging and manipulations. Mitochondrial DNA copy number and mitochondrial respiratory function are reduced when functional and structural manifestations of vascular aging begin. Rescue of the copy number deficit observed in normal aging improves mitochondrial respiration and delays all parameters of vascular aging, while reduced mtDNA integrity accelerates vascular aging. Together these data highlight the direct role of mtDNA-mediated mitochondrial dysfunction in the progression of vascular aging.