Uric Acid Levels Pose Potential Harm in Accelerating Biological Aging

A new study revealed circulating uric acid have a potential role in accelerating biological aging among older adults.¹

“These results clinically underscore the potential of circulating [uric acid] as a pro-aging factor rather than an anti-aging one in this demographic,” wrote investigators, led by Min-gu Kang, from Chonnam National University Bitgoeul Hospital in South Korea. “Moreover, this research adds to the growing body of evidence that suggests serum UA could serve as a potential blood-based biomarker for detecting frailty in older adults.”

The roles of uric acid contradict each other. While uric acid serves as an inflammatory mediator, it also serves as an antioxidant.^2,3 Investigators aimed to see if circulating uric acid was harmful or beneficial to the health of older adults.¹ They assessed the association between serum uric acid concentrations and the frailty index; the frailty index was selected since it is a comprehensive measure of biological aging.

The team conducted a population-based, cross-section study, leveraging data of 4268 participants aged ≥ 65 years from the Korea National Health and Nutrition Examination Survey. The frailty index used included 38 items that evaluated physical, cognitive, psychological, and social domains.

Based on the frailty index results, participants were placed into the groups non-frail (frailty index: ≤ 0.15; 30.4% of participants; mean age: 71 years), pre-frail (frailty index: > 0.15 but ≤ 0.25; 41% of participants; mean age: 72.9 years), or frail (frailty index: > 0.25; 28.6% of participants; mean age: 74.4 years). Gender distribution was significantly different for the groups. In the groups, 51.8% of non-frail participants, 43% of pre-frail participants, and 33.3% of participants were male (P < .001). Investigators analyzed serum uric acid levels through a colorimetric enzymatic assay.

The team analyzed the comorbidities of age, sex, socioeconomic status, lifestyle factors such as smoking status, medical history, and body mass index (BMI). Analyses showed socioeconomic and health characteristics, including lower income, less education, greater number of smokers, and a greater prevalence of hypertension, diabetes, dyslipidemia, stroke, cardiovascular diseases, and increased BMI worsened progressively from non-frail to frail groups (P < .001).

A linear analysis demonstrated uric acid levels increased as frailty severity increased from non-frail to frail (P = .002). Frail adults presented with greater serum uric acid levels than non-frail adults (P = .002).

After adjusting for age, sex, and other comorbidities, investigators found serum uric acid levels were significantly greater in frail participants than in non-frail participants (P < .001). The study showed serum uric acid concentrations were positively correlated to the frail index (P < .001).

Moreover, per 1 mg/dL increase in serum uric acid, the odds for frailty were 1.22 (95% confidence interval [CI], 1.12 – 1.33; P < .001), and the risks were 25% and 22% as shown in the age- and sex-adjusted and multivariable-adjusted models, respectively (P < .001).

Furthermore, older adults with the greatest levels of uric acid (quartile 4; uric acid > 5.8 UA mg/dL) had had significantly greater frail indexes than older adults with the lowest levels of uric acid (quartile 1; serum uric acid ≤ 4.1 mg/dL) in both the age- and sex-adjusted (P < .001) and multivariable-adjusted models (P = .011). Also, logistic regression analyses found that, compared to older adults in the lowest quartile of uric acid levels (P = .005), older adults in the highest quartile had 1.66-fold increased odds of frailty (P = .011).

Investigators also divided participants into 2 groups based on uric acid levels, separately for men and women, to examine hyperuricemia (≥ 7 mg dL for men and 6 mg/dL for women). The hyperuricemia group for both men and women had a significantly greater frailty index compared with those without hyperuricemia (P < .001). Logistic regression analyses of the unadjusted model showed older adults in the hyperuricemia group had 2.33-fold and 4.30-fold greater odds for frailty in men and women, respectively. The odds remained consistent after adjusting for potential confounders for both men (P = .016) and women (P < .001).

“…findings from a nationally representative cohort indicate that elevated serum [uric acid] levels are robustly linked with an increased frailty index that encompasses physical, cognitive, psychological, and social dimensions, as well as an elevated risk of frailty among older adults,” investigators concluded. “Future studies are warranted to explore whether interventions aimed at lowering [uric acid] levels can ameliorate oxidative stress and inflammatory responses, ultimately contributing to improved biological aging outcomes.”

References

• ^{Kang MG, Baek JY, Jo Y, et al. Higher serum uric acid as a risk factor for frailty in older adults: A nationwide population-based study. J Cachexia Sarcopenia Muscle. Published online August 18, 2024. doi:10.1002/jcsm.13561}
• ^{Kanbay M, Segal M, Afsar B, Kang DH, Rodriguez-Iturbe B, Johnson RJ. The role of uric acid in the pathogenesis of human cardiovascular disease. Heart 2013; 99: 759–766.}
• ^{Babio N, Martínez-González MA, Estruch R, Wärnberg J, Recondo J, Ortega-Calvo M, et al. Associations between serum uric acid concentrations and metabolic syndrome and its components in the PREDIMED study. Nutr Metab Cardiovasc Dis 2015; 25: 173–180.}