Abstract
Monoamine Oxidase A (MAO-A) and Monoamine Oxidase B (MAO-B) are flavin-dependent enzymes that progressively increase with age in many tissues. It is proposed that both serve as “death genes,” depleting Flavin Adenine Dinucleotide (FAD) and thereby reducing mitochondrial energy production—mirroring the known action of CD38, which depletes Nicotinamide Adenine Dinucleotide (NAD+). Although MAO-A retains certain developmental and sex-related roles, MAO-B appears to confer no clear early-life benefit and emerges as the first true, fully dedicated death gene documented. This discovery challenges classical evolutionary theories and suggests an unexpected “programming” of aging. The contrasting knockout phenotypes are detailed—dramatic aggression and neurotransmitter imbalance for MAO-A vs. subtle or minimal deficits for MAO-B. How the parallel depletion of NAD+ (by CD38) and FAD (by MAOs) undermines electron transport chain function in a near-symmetric manner is also examined. These findings open new therapeutic possibilities, including targeted inhibition of MAO-B (and MAO-A) and combined strategies preserving both NAD+ and FAD to mitigate age-related decline. This finding also calls into question a core principle of the selfish gene theory of evolution and suggests a need for a reevaluation of mainstream theory.