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Systemic extracellular acidification is a hallmark of ageing

ABSTRACT: Finding 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.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE263182 | GEO | 2026/04/01

REPOSITORIES: GEO

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Project description:Increasing atmospheric CO2 concentrations are causing decreased pH over vast expanses of the ocean. This decreasing pH may alter biogeochemical cycling of carbon and nitrogen via the microbial process of nitrification, a key process that couples these cycles in the ocean, but which is often sensitive to acidic conditions. Recent reports indicate a decrease in oceanic nitrification rates under experimentally lowered pH. How composition and abundance of ammonia oxidizing bacteria (AOB) and archaea (AOA) assemblages respond to decreasing oceanic pH, however, is unknown. We sampled microbes from two different acidification experiments and used a combination of qPCR and functional gene microarrays for the ammonia monooxygenase gene (amoA) to assess how acidification alters the structure of ammonia oxidizer assemblages. We show that despite widely different experimental conditions, acidification consistently altered the community composition of AOB by increasing the relative abundance of taxa related to the Nitrosomonas ureae clade. In one experiment this increase was sufficient to cause an increase in the overall abundance of AOB. There were no systematic shifts in the community structure or abundance of AOA in either experiment. These different responses to acidification underscore the important role of microbial community structure in the resiliency of marine ecosystems. amoA gene diversity from two ocean acidification experiments, Monterey Bay experiment (two time points, ambient and acidified) and Vineyard Sound experiment (ambient and acifidied, with and without nutrients) examined with 2 two-color arrays (Cy3 and Cy5): the universal standard 20-mer oligo is printed to the slide with a 70-mer oligo (an archetype). Environmental DNA sequences (fluoresced with Cy3) within 15% of the 70-mer conjugated to a 20-mer oligo (fluoresced with Cy5) complementary to the universal standard will bind to the oligo probes on the array. Signal is the ratio of Cy3 to Cy5.

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Systemic extracellular acidification is a hallmark of ageing

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