"Urological age" as a proxy of healthy longevity: analysis of prospective population-based cohorts in U.S. and China

Abstract

Background: Assessing urinary symptoms poses a complex challenge for primary care practitioners. In evaluating urological function, authors' approach involves constructing an urological age through the analysis of laboratory parameters and indicators of the urinary system.

Methods: Based on the National Health and Nutrition Examination Survey (NHANES), urological laboratory tests and age-related symptoms were included in the development of urological age (UA) and urological age acceleration (UAA) through the Klemera Doubal method. In relation to mortality associated with UAA, the metric was categorized into grades (0, 1, 2) as a discrete variable. The authors investigated the correlation between UAA and its grades with mortality, conducted survival analysis based on UAA grades, and explored the correlation between multi-system ageing-related disorders and UAA grades based on the NHANES and the West China Natural Population Cohort Study.

Results: UA was related to age with the r to 0.85 in men and 0.84 in women. Each year the increase in UAA was related to higher 1% and 4% mortality for men and women. Those with UAA grades 1 and 2 were associated with more risk of mortality than individuals with UAA grade 0 (men 8% and 40%, women 24% and 157%). The advanced UAA grades kept pace with multi-system ageing. Healthy diets and lifestyle habits are associated with lower UAA.

Conclusion: Urological age is related to multi-system ageing and increases mortality risk, and urological age can be used to screen high-risk individuals and inform precision clinical development for ageing intervention.

Figure 1

Urological age model and development. (A) The construction and validation of urological age. The icons used in the figures of this study were obtained from BioRender.com. (B) The correlation between urological indicators and age. (C) The association between each urological indicator. (D) Calculate the equation for urological age. NHANES is the National Health and Nutrition Examination Survey. WCNPCS is the West China Natural Population Cohort Study. x is the measured value of the biomarker. For each biomarker i, the parameters k, q, and s are derived from regression estimates of the calendar age of the biomarkers in the reference sample. k, q, and s are the regression intercept, slope, and root mean square error, respectively. The s _KD is a scaling factor equal to the square root of the variance of calendar age explained by the biomarker set in the reference sample. CA is the chronological age. BUN, blood urea nitrogen; PSA, prostate-specific antigen; SBP, systolic blood pressure; SUI, stress urinary incontinence; UUI, urge urinary incontinence.

Figure 2

Urological age, UAA, and UAA grades. (A) The correlation between urological age and age among men and women. (B) Receiver operating characteristic curve about the prediction of UA on mortality. (C) The association between UAA and mortality. Model 1: adjusted for age, race, education and poverty income ratio. Model 2 adjusted for age, race, education, poverty income ratio, BMI, drinking and smoking. (D) The distribution of UAA in participants and the cut-off points of UAA for UAA grades, which were evaluated by X-tile. AUC, area under the curve; HR, hazard ratio; UAA, urological age acceleration.

Figure 3

Survival analysis based on the UAA grades. (A) UAA grades and following time. (B). Survival analysis based on the UAA grades among men and women. (C) The association between UAA grades and all-cause mortality. HR, hazard ratio; UAA, urological age acceleration.

Figure 4

The association between UAA grades and multi-system ageing among men and women. The association between ageing-related disorders and UAA grades. (A) Activities of daily living (ADL) and instrumental activities of daily living (IADL). (B) The Patient Health Questionnaire (PHQ) score and depression. (C) Cardiometabolic index and cardiovascular diseases. (D) Neutrophil-to-lymphocyte ratio and C-reactive protein. The association adjusted for age, race, education, poverty income ratio, BMI, drinking, smoking, met. UAA, urological age acceleration.

Figure 5

Urological age and health correlations in WCNPCS, and the association between lifestyles and urological age acceleration (UAA) in NHANES. (A) The association between urological age and age is based on WCNPCS. (B) The association between urological age acceleration and health indicator. (C) The association between lifestyles and UAA in NHANES. The associations were adjusted for age, race, education, poverty income ratio, and BMI. ADL, difficulties in activities of daily living; CDAI, composite dietary antioxidant index; CMI, the cardiometabolic index; CVD, cardiovascular diseases; DII, Dietary Inflammatory Index; IADL, difficulties in instrumental activities of daily living; LE8, Life’s Essential 8; MET, the metabolic equivalent; NLR, the neutrophil-to-lymphocyte ratio; OBS, oxidative balance score; PHQ, Patient Health Questionnaire; SII, systemic immune-inflammation index; SWLS, Scale to Measure Satisfaction with Life.