Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake

Abstract

BackgroundWe have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health.ResultsWe observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption.ConclusionsAccelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status.

The role of the microbiota in sedentary lifestyle disorders and ageing: lessons from the animal kingdom

“…Indeed, human progerias, such as Hutchinson's Guilford's syndrome, or a disease of accelerated ageing, such as CKD, display elevated serum phosphate levels . Epidemiological studies have indicated that frequent consumption of red meat is a source of age‐related hyperphosphataemia in man . This offers a mechanistic basis for age‐related health, inflammatory burden (inflammageing) and alterations in the composition and role of the microbiota.…”

“…A sub-optimal foodome can lead to an aberrant microbiome with consequential health effects, typically mediated by accelerated ageing, whereby the hallmarks of normative ageing become dysregulated, metabolic morbidity is facilitated and the diseasome of ageing is ensues at an earlier chronological age syndrome, or a disease of accelerated ageing, such as CKD, display elevated serum phosphate levels [44]. Epidemiological studies have indicated that frequent consumption of red meat is a source of age-related hyperphosphataemia in man [46]. This offers a mechanistic basis for age-related health, inflammatory burden (inflammageing) and alterations in the composition and role of the microbiota.…”

The role of epigenetics in renal ageing

“…It is a proatherogenic and pro-inflammatory compound that provides a mechanistic link between excess red meat consumption in man linked to both hyperphosphatemia and accelerated aging. 145,149,150 Notably in these studies, less than 25% of inter-individual variation in inflammatory status was explainable by biological age, 143 or methylation levels, 151 which suggest that the microbiome might have a larger impact on inflammation than anticipated based on a pre-existing hypothesis of a linear relationship between biological age and SASP related inflammatory status.…”

“…Notably, recent evidence has indicated that this is also independently associated with nutritionally-driven hyperphosphatemia, due to frequent red meat and processed meat consumption. 145 These findings are also relevant to the growing incidence of CKD globally and indicate that nutritionally driven hyperphosphatemia associated with lower socioeconomic status and poor eating habits are potential contributory factors to CKD and chronic inflammation. 145 The question then arises how nutritionally acquired phosphate affects the epigenome?…”

“…Firstly, nutritionally derived hyperphosphatemia with concomitant tubular injury and interstitial fibrosis due to calciprotein particle (CPP) generation, and genomic hypomethylation, occurring independently of telomere attrition. 145 Unsurprisingly, the odds ratio of developing CKD is higher in healthy subjects with a serum Pi >4mg/dL 152 and a high red meat intake 153 Additionally, translocation of gut microbiota (and, or endotoxins) into the circulation via disruption, or leakage, at colonic epithelial tight junctions through altered occludin and claudin expression might also be at play. 154,155 Dysfunction of tight junction proteins has also been reported to result in reduced nuclear factor erythroid 2-related factor 2 (Nrf2) expression, thus elevating oxidative stress levels.…”