Using comparative biology to understand how aging affects mitochondrial metabolism

- The use of comparative biology is a valuable approach for uncovering biochemical mechanisms of aging.
- We propose that post translational modifications in the form of hyperacylation may be the cause of some mitochondrial deficiencies associated aging.
- Maintaining NAD + -dependent deacetylase SIRT3 activity, which removes mitochondrial acetyl groups, may be essential for maintaining lifespan and healthspan.

Lifespan varies considerably among even closely related species, as exemplified by rodents and primates. Despite these disparities in lifespan, most studies have focused on intra-specific aging pathologies, primarily within a select few systems. While mice have provided much insight into aging biology, it is unclear if such a short-lived species lack defences against senescence that may have evolved in related longevous species. Many age-related diseases have been linked to mitochondrial dysfunction that are measured by decreased energy generation, structural damage to cellular components, and even cell death. Post translational modifications (PTMs) orchestrate many of the pathways associated with cellular metabolism, and are thought to be a key regulator in biological senescence. We propose hyperacylation as one such modification that may be implicated in numerous mitochondrial impairments affecting energy metabolism. Keywords: Comparative biology, Sirtuin 3, Acylation, Mitochondria, Aging