Limited Food, Declining Glycolytic ATP Production, and the Evolution of Aging
Researchers here mount an argument for aging to have evolved due to the interaction between (a) limited nutrient availability in the environment and (b) the options a cell has for generating the vital chemical energy store molecule adenosine triphosphate (ATP). Broadly, ATP can be generated via glycolysis in the cytoplasm or oxidative reactions in mitochondria, at least in eukaryotes such as mammals. Mitochondrial ATP production is slower and more energy-efficient, but both avenues decline with age. Loss of ATP production is harmful to cell and tissue function, most prominently in tissues with high energy needs such as muscle and the brain. Why does ATP production decline with age? The argument advanced here is that this decline evolved in part because it helps the survival of offspring by limiting parental consumption of resources, which borders on being a group selection mechanism. Group selection has long fallen out of favor, but a number of theories of aging, particularly those in the programmed aging category, have considered it to one degree or another.
Why do animals not have an eternal lifespan? Animals possess sophisticated systems that, in many species, appear capable of supporting immortality. Second, why do lifespans vary considerably among species despite similarities in genetic makeup, specifically the central dogma linking DNA, RNA, and protein synthesis, which warrants a molecular explanation? For example, elephants live thirty times as long as mice.
Significant differences between ATP production by glycolysis and oxidative phosphorylation include the quantity produced, production speed, and functional roles. Glycolytic ATP production is approximately 100 times faster than oxidative phosphorylation. ATP from glycolysis supplies rapid energy during acute demands, while oxidative phosphorylation supports basal/homeostatic cellular energy needs. Glycolysis plays important role in cell division and DNA repair. Additionally, the glycolysis activator HIF-1α promotes mitochondria repair through mitophagy. These findings suggest that decreased glycolytic ATP production during aging may underline various age-related symptoms. Immortal cells exhibit a metabolic profile characterized by highly active glycolytic ATP production and HIF-1α activation, even in oxygen-rich conditions.
Populations of species cannot grow infinitely, and one of the major limiting factors in natural world is food supply. The shift from glycolysis to aerobic metabolism increases energy efficiency, benefiting individual survival during food shortages, which can be caused by environmental changes or emergence of competitors for the food. This indicates that reduced glycolytic ATP production with aging can benefit the species by enhancing survival of parent generation at starvation conditions and allocating food to offspring generation in natural world where food supply is limited. Only species that happened to have an optimal rate of reduction in glycolytic ATP production over time were selected and survived through generational changes.
The optimal rate of glycolytic ATP decline for survival varies among species and depends on factors such as environment, competition, maturation time, and body size. This concept clarifies the significant differences in aging rates and lifespans across species despite largely conserved biological components. This is exemplified by the naked mole rat, an exceptionally long-lived species that lives underground where there are few environmental changes and predators, and maintains unrestrained glycolytic flux and ATP supply to adapt to underground life with low oxygen levels.