Higher gene expression stability during aging in long-lived giant mole-rats than in short-lived rats

Abstract

Many aging-associated physiological changes are known to occur in short- and long-lived species with different trajectories. Emerging evidence suggests that numerous life history trait differences between species are based on interspecies variations in gene expression. Little information is available, however, about differences in transcriptome changes during aging between mammals with diverging lifespans. For this reason, we studied the transcriptomes of five tissue types and two age cohorts of two similarly sized rodent species with very different lifespans: laboratory rats (Rattus norvegicus) and giant mole-rats (Fukomys mechowii), with maximum lifespans of 3.8 and more than 20 years, respectively. Our findings show that giant mole-rats exhibit higher gene expression stability during aging than rats. Although well-known aging signatures were detected in all tissue types of rats, they were found in only one tissue type of giant mole-rats. Furthermore, many differentially expressed genes that were found in both species were regulated in opposite directions during aging. This suggests that expression changes which cause aging in short-lived species are counteracted in long-lived species. Taken together, we conclude that expression stability in giant mole rats (and potentially in African mole-rats in general) may be one key factor for their long and healthy life.