A groundbreaking study from Federation University Australia has uncovered a critical biological marker that identifies individuals whose kidneys are ageing faster than their chronological age, putting them at significantly higher risk for chronic kidney disease (CKD). Dubbed 'fast agers,' these people exhibit accelerated telomere shortening in kidney cells combined with specific epigenetic changes, leading to nephrosclerosis—the hardening and scarring of kidney tissue that drives disease progression.

Led by Dr. Olutope Arinola Akinnibosun, the research analyzed tissue samples from 200 participants using the world's largest human kidney tissue resource. This work, published in Cardiovascular Research, reveals that kidney biological age often diverges from that measured in blood or skin, offering a more precise tool for risk assessment.

Chronic kidney disease affects approximately 1.7 million Australian adults, or 11% of the population aged 18 and over, with prevalence skyrocketing to 44% in those over 75. Often dubbed a 'silent killer,' CKD remains asymptomatic until advanced stages, when dialysis or transplantation becomes inevitable.

Biological age refers to the physiological state of organs and tissues, determined by molecular markers like telomere length and DNA methylation patterns, rather than calendar years. Telomeres, the protective caps at chromosome ends, naturally shorten with cell divisions, accelerating in 'fast agers' due to oxidative stress, inflammation, or genetics.

In kidneys, this shortening correlates with nephrosclerosis, independent of traditional risk factors like hypertension or diabetes. Epigenetic clocks—patterns of chemical tags on DNA—further refine this measure, capturing cumulative environmental and lifestyle impacts.

Studies show fast agers face heightened risks for cardiovascular events, cognitive decline, and mortality. For kidneys specifically, accelerated ageing predicts faster glomerular filtration rate (eGFR) decline, a key CKD metric.

This Federation study highlights why blood-based clocks fall short: kidney cells experience unique stressors from constant filtration, making tissue-specific analysis essential.

Dr. Akinnibosun's team collaborated with University of Manchester experts to examine healthy kidney biopsies from surgical patients. Using advanced techniques, they quantified telomere length via quantitative PCR and mapped epigenetic signatures through methylation arrays.

Participants spanned ages 20-80, allowing comparison of chronological versus biological age. Statistical models adjusted for confounders like sex, BMI, and smoking, isolating ageing effects.

Key innovation: integrating telomere data with epigenetic clocks tailored to kidney tissue, revealing a signature for fast agers—those with kidneys biologically 5-10 years older.

Shorter kidney telomeres strongly predicted nephrosclerosis (p<0.001), linking to reduced eGFR and glomerulosclerosis. Fast agers showed 20-30% greater telomere attrition, accompanied by hypermethylation at ageing-related CpG sites.

This duo—telomere loss plus epigenetic shifts—distinguished high-risk profiles before clinical symptoms. Younger fast agers (under 50) mirrored 70-year-olds' kidney profiles, underscoring early intervention needs.

Unlike blood clocks, kidney-specific metrics correlated directly with histopathology scores, validating their superiority.

Kidneys filter 180 liters of blood daily, exposing cells to toxins and shear stress, hastening telomere erosion. Unlike skin, renal cells divide less but accumulate damage faster in susceptible individuals.

Fast agers often harbor genetic variants impairing telomerase (telomere repair enzyme) or heightened inflammation. Australian cohorts show Indigenous populations at 3-4x CKD risk, potentially tied to accelerated renal ageing.

Lifestyle amplifies this: high-salt diets, prevalent in Australia, exacerbate nephrosclerosis in fast agers.

Photo by berenice melis on Unsplash

Australia faces a CKD crisis: 1 in 10 adults affected, costing $10B annually. Incidence rises 5% yearly, driven by diabetes (40% cases) and hypertension. By 2030, projections estimate 2.5M cases amid ageing demographics.

Mortality: CKD ranks 9th killer, with 8,000 deaths/year. Disparities stark—Indigenous rates 4x higher. Early biomarkers could avert 30% progressions via screening.AIHW CKD Report

• Prevalence: 11% adults, 44% >75yo
• Risk factors: Age, diabetes, HTN, obesity
• Undiagnosed: 90% stage 1-3

Current eGFR/creatinine tests miss early decline. Federation's markers enable pre-symptomatic ID via biopsy or future non-invasive proxies (urine exosomes?).

Dr. Akinnibosun notes: “By measuring these changes at a genetic level, we can identify ‘fast kidney agers’... personalise treatment.” Integration into routine checkups could halve late diagnoses.

Trials underway for blood-based telomere/epigenetic assays, promising GP-level screening.

Fast agers benefit most from targeted changes: low-sodium DASH diet, exercise (150min/week), smoking cessation. SGLT2 inhibitors (e.g., dapagliflozin) slow decline 30-40% in high-risk.

• Exercise: Boosts telomerase 20%
• Plant-based: Reduces epigenetic age 3.5yrs
• Metformin: Potential anti-ageing

For researchers, explore telomerase activators. Check research assistant roles in ageing studies.

Dr. Akinnibosun, a genomics expert, builds on prior hypertension work. Manchester partnership leverages UK biobanks. Peers praise: “Pioneering tissue-specific clocks.”

Federation's Cardiovascular Research Group advances precision medicine. Explore Australian uni jobs in biomed.Full Paper

Next: Validate in longitudinal cohorts like AusDiab. AI models predict fast agers from wearables. Gene therapies targeting telomerase loom.

Higher ed role: Federation trains next-gen via PhDs. View research jobs.

Photo by Danny Howe on Unsplash

Federation exemplifies Aus unis' impact, securing grants amid funding squeezes. Interdisciplinary teams drive biomarkers from bench to bedside. Aspiring academics, peruse postdoc advice.

This study heralds a proactive CKD era, empowering fast agers to reclaim health. Early action via biomarkers promises fewer transplants, better lives. Stay informed via Rate My Professor, Higher Ed Jobs, Career Advice. Explore uni jobs or post yours.