Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures.

This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.

Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, ³Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA.

This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.

Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.

Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration.

With the growing older population, ensuring effective, accessible nutritional support within primary care as a first line of medical care is becoming increasingly important. Nutritional counselling is a promising approach to enhancing health outcomes and independence among older adults. However, a stronger evidence base is needed to assess its true effect and inform clinical decisions. Additionally, food insecurity remains an under-recognised issue in this population and is often overlooked in primary care settings. This highlights the need for simple, practical methods to identify those at risk. This study aimed to assess the effectiveness of nutritional intervention provided to older people and determine which nutrients may indicate food insecurity in primary care settings in Tehran.

The study will be conducted in two phases. The first phase is a prospective cohort study (single cohort). The second phase is a cross-sectional study on older people who refer to primary care settings affiliated with the Tehran University of Medical Sciences. In the first phase, the effectiveness of nutritional interventions – including counselling and diet – is evaluated based on anthropometric indicators (weight, waist circumference, calf circumference, arm circumference and waist-to-height ratio), blood pressure and scores from the Mini Nutritional Assessment, health-related quality of life, dietary intake and physical activity. Assessments will be evaluated prospectively at the beginning of the study, after 3 months, and at the end of the study. In the second phase of the cross-sectional study, by examining dietary intake and food insecurity, we will identify the specific nutrient or food group that serves as an indicator of food insecurity in the diet of older individuals. Intakes below 50% and 75% of the recommended daily allowance will be analysed. Through sensitivity and specificity analysis, we will identify which nutrient or food group is strongly associated with food insecurity in older people.

This study received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICINE.REC.1402.474). Study findings will be disseminated through peer-reviewed journal articles, presentations at national and international conferences and meetings with the Iranian Ministry of Health, facility and community stakeholders.

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