GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE263nnn/GSE263182/primaryOK200TranscriptomicsDrosophila melanogasterExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE263182GEOGSEfalseSystemic extracellular acidification is a hallmark of ageingFinding the critical pathophysiological processes that promote disease risk with age is needed to uncover effective targets for preventive medicine. Despite being essential for physiology at all levels, the behaviour of protons in bodily fluids is understudied in ageing. Here, we investigate how extracellular pH changes with age and its impact on longevity, using Drosophila melanogaster and rodent models. Extracellular acidification occurs in flies during ageing and correlates with mortality rate, independently of strain, sex and diet. With age, flies also become more susceptible to die from acidotic stress, which can be prevented by alkalotic treatment. Acidification is caused by insufficient acid excretion, linked to downregulation of genes in the fly excretory tract that control pH and ATP production, essential for active secretion initiation. In rodents, we demonstrate that lymph also acidifies with age. Genes whose pathogenic variants cause tubular acidosis in humans are downregulated in the kidneys of ageing mice. Overall, this study sheds light on dysregulated systemic acid-base balance as a conserved pathophysiological mechanism of ageing.2026/04/01GSE263182GSM8187270GSM8187271GSM8187260GSM8187263GSM8187264GSM8187272GSM8187261GSM8187262GSM8187267GSM8187256GSM8187268GSM8187257GSM8187265GSM8187266GSM8187255GSM8187269GSM8187258GSM818725930203263182Drosophila melanogaster