Researchers interested in the comparative biology of aging have focused much of their efforts on the search for genetic differences that correlate with species life span. This can be higher or lower expression in directly homologous genes, but also differences in the number of genes in a family relating to a specific function, and differences in gene sequences. As one might expect, well established genetic differences involve genes associated with mechanisms relevant to aging and life span, such as DNA repair, tumor suppression, regenerative capacity, and antioxidant mechanisms.
In today's open access paper, researchers describe a more comprehensive search for differences between mammalian species, and find that genetic differences are more related to immune system function and brain size relative to body size than they are to body size alone. This is interesting; as you might recall, body size and metabolic rate correlates decently well with species longevity. Bigger animals tend to live longer than smaller animals, and exhibit a slower metabolism. The outliers are extreme, however, such as naked mole rats that live nine times as long as similarly sized mice and tiny bats that live for decades. The outliers show there is no necessary dependency on body size, and that the real mechanisms are elsewhere. That one of those mechanisms is the state of the immune system will keep researchers busy for a while: it is a very complex, incompletely understood part of mammalian biology.
Mammals exhibit high diversity in their maximum lifespan potential (MLSP, the age at death (longevity) of the longest-lived individual ever recorded in a species), ranging from less than a year in some shrew species to over a hundred years in humans and up to two hundred in bowhead whales. Unlike average lifespan, which reflects both intrinsic and extrinsic factors such as the risk of predation and resource availability, MLSP is assumed to reflect a species' inherent longevity limit and is widely available used in comparative studies focused on life history trade-offs and the genomic determinants of longevity.
Identifying the overarching genomic signatures associated with the evolution of MLSP can provide insights into the evolution of key life history traits and variations in longevity between individuals in a species. Comparative studies have linked MLSP variations to changes in gene expression profiles. Genes associated with MLSP in these studies were enriched in DNA repair, defence response, cell cycle, and immunological process related terms. Genes such as PMS2 (DNA repair), PNMA1 (cell fate determination), and OGDHL (reactive oxygen species regulation) show positive correlation with MLSP across mammalian tissues. BCL7B, which inhibits carcinogenesis through Wnt pathway regulation, and GATM, associated with oxidative stress protection, are prominently linked to increased lifespan. These molecular signatures collectively enhance cellular maintenance and stress resistance mechanisms that appear critical for extended longevity.
Here, we use a comparative genomics approach to identify genomic signatures associated with the evolution of MLSP across mammals. We examine whether MLSP variations correlate with gene family sizes (of protein-coding genes) in 46 fully sequenced mammalian species. We found significant gene family size expansions associated with maximum lifespan potential and relative brain size but not in gestation time, age of sexual maturity, and body mass in 46 mammalian species. Extended lifespan is associated with expanding gene families enriched in immune system functions. Our results suggest an association between gene duplication in immune-related gene families and the evolution of longer lifespans in mammals.
View the full article at FightAging
