Comparing the Mitochondria of Mice and Long-Lived Bats
Like naked mole-rats, bats are outliers among mammals when it comes to metabolism and longevity. They live much longer than similarly-sized mammals. We can hypothesize that the demands of living in oxygen-poor underground environments, in the case of naked mole-rats, and the demands of flight, in the case of bats, leads to a more resilient cellular biochemistry. That in turn has the side-effect of greater longevity. Much of the investigation of this hypothesis is focused on mitochondria, the power plants of the cell, and their differing composition between species. The membrane pacemaker view of aging suggests that species differences in life span among mammals arise in large part due to the degree of resistance to oxidation of cell membranes, particularly those of mitochondria. Mitochondrial function is critical to tissue function, and aging is associated with a growing malaise in mitochondria: poor quality control, rising levels of damage and dysfunction.
Some common observations have been used to generate theories of ageing. The rate of living theory of ageing proposes to explain the variation in mammalian lifespans, it states that lifespan and metabolic rate are inversely correlated. Another theory is the mitochondrial free radical theory of ageing, this states that animals with high basal metabolic rates will generate greater levels of reactive oxygen species (ROS) and due to their detrimental effect, have shorter lifespans. Observed mammalian biology mostly aligns with these theories however there are a few notable exceptions, including the naked mole rat and microbats, that live much longer than their small body size and high metabolic rates would predict.
Microbats are exceptionally long-lived considering their small body size and high metabolic rates. For instance, the maximum lifespan for the bat; Myotis lucifugus (weight ~8g) is 34 years. In comparison the maximum lifespan of a mouse (Mus musculus) (weight ~30g) is 4 years. Bats have been shown to expend double the amount of energy in comparison to non-flying eutherian mammals and yet they live on average three times longer than non-flying eutherian mammals. This raises the question; how do bats maintain such high metabolic rates without succumbing to accumulating damage over their lifespan?
Oxidative stress has been a key focus for the majority of studies investigating longevity in bats. Mitochondrial dysfunction is evident in ageing and age-related diseases. Mitochondrial DNA (mtDNA) is considered to be more susceptible to mutagenesis due to the close proximity of mtDNA to ROS and also the high number of direct repeat regions prone to deletions. Bat mtDNA was found to have a lower number of repeat regions compared with other mammals. Bats were found to produce half to one third of the amount of hydrogen peroxide per oxygen molecular consumed compared to both shrews and mice. Research thus far indicates that bats produce less ROS and may also be more resistant to oxidative stress.
In this study we compared the mitochondrial lipidome and proteome of whole brain and skeletal tissues from adult Pipistrelle bats (maximal lifespan 12 years) with parallel sample types prepared from young and middle-aged Mus musculus. We used proteomics and ultra-high-performance liquid chromatography coupled with high resolution mass spectrometry lipidomics, to interrogate mitochondrial fractions prepared from tissues. Fatty acid binding protein 3 (FABP3) was found at different levels in mouse and bat muscle mitochondria and its orthologues were investigated in Caenorhabditis elegans knock-downs for LBP 4, 5, and 6. In the bat, high levels of free fatty acids and N-acylethanolamine lipid species together with a significantly greater abundance of FABP3 in muscle were found. We show that decreased quantities of FABP3 orthologues are detrimental to mitochondrial health. The literature supports this as a mechanism associated with mitochondrial dysfunction across many tissues. Mechanisms to increase levels of FABP3 or fatty acids in the mitochondrial compartment may be of interest in supporting mitochondrial health through the lifespan.