What Can Be Learned About Energy Metabolism and Longevity from Birds?

Here find an interesting commentary on some of the evolved genetic differences between mammals and birds, with a focus on genes relevant to energy metabolism - and potentially to species longevity. Larger animals live longer, but birds tend to be long-lived for their size. This is also the case for some bat species. It is thought that adaptations to energy metabolism needed to support the very energy-intensive activity of flight are involved in this increased longevity, providing resilience as a side effect.

The details have yet to be mapped in any comprehensive way, but studies such as today's open access example are steps towards that goal. Energy metabolism is closely associated with mitochondrial function and oxidative stress, both of which appear strongly connected to processes of aging. Loss of mitochondrial function and rising oxidative stress are features of aging, but in the short term are also features of exertion. It is plausible to argue that systems that evolved to cope with and minimize the side effects of high energy expenditure seem likely to also increase longevity. It is perhaps interesting that this isn't universal, that we do still see comparatively short-lived birds and bats despite their capability of flight.

As with all such research, it is an open question as to whether there is anything to find that could form the basis for near-term therapies in humans. In the much longer term, rebuilding human biology from the ground up will certainly take place, incorporating everything learned from a study of comparative biology, and likely going beyond to the production of wholly artificial biological systems that are better yet, but those of us reading this now only have so much time on hand to await treatments capable of producing longer healthy life spans.

Gene purging and the evolution of Neoave metabolism and longevity

Aves emerged from bipedal dinosaurs ∼165-150 million years ago (MYA), survived the Cretaceous-Paleogene extinction event 66 MYA, and then diversified into the ∼10,000 Neoaves species we observed today. The benefits of becoming endothermic, smaller, and adapted for flapping-wing flight allowed for greater foraging opportunities, predator avoidance, and tolerance to a great range of environments. The power required to fly long distances is largely a multiple of basal metabolic rates (BMR), and smaller birds with proportionately more fat reserves can fly longer distances than large birds. Indeed, genes involved in energy metabolism show strong evidence of positive selection, suggesting early adaptative mutations required for flight. Body mass correlates with BMR and longevity, although shifts and variation across vertebrate phylogeny remain unexplained. Many Neoaves are outliers, showing greater longevity and higher BMR than expected relative to body size.

Maintenance of the proteasome requires oxidative phosphorylation to produce ATP and mitigation of oxidative damage, in an increasing dysfunctional relationship with aging. SLC3A2 plays a role on both sides of this dichotomy as an adaptor to SLC7A5, a transporter of branched-chain amino acids (BCAA), and to SLC7A11, a cystine importer supplying cysteine to the synthesis of the antioxidant glutathione. Endurance in mammalian muscle depends in part on oxidation of BCAA, however elevated serum levels are associated with insulin resistance and shortened lifespans. Intriguingly, the evolution of modern birds (Neoaves) has entailed the purging of genes including SLC3A2 and SLC7A5, largely removing BCAA exchangers in pursuit of improved energetics.

Additional gene purging included mitochondrial BCAA aminotransferase (BCAT2), pointing to reduced oxidation of BCAA and increased hepatic conversion to triglycerides and glucose. Fat deposits are anhydrous and highly reduced, maximizing the fuel/weight ratio for prolonged flight, but fat accumulation in muscle cells of aging humans contributes to inflammation, and senescence. Duplications of the bidirectional α-ketoacid transporters SLC16A3, SLC16A7, the cystine transporters SLC7A9, SLC7A11, and N-glycan branching enzymes MGAT4B, MGAT4C in Neoaves suggests a shift to the transport of deaminated essential amino acid, and stronger mitigation of oxidative stress supported by the galectin lattice.