Accelerated Aging Linked to Greater Risk of Rheumatoid Arthritis

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In a new study, cross-sectional analyses showed each 1-year increase in age-adjusted biological age was linked to a 1% - 10% increase in the risk of rheumatoid arthritis.

Accelerated Aging Linked to Greater Risk of Rheumatoid Arthritis

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Accelerated aging is linked to a greater increase in rheumatoid arthritis (RA), particularly for individuals with a high genetic risk, and could reduce life expectancy, according to a new study.1

Previous research found RA affects life expectancy, taking off a mean of 10 years.2 In 2017, the age-standardized disability-adjusted life-years for RA was 43.3 per 100,000 population.1

Although accelerated aging, a premature decline in homeostasis, is believed to be a major risk factor for age-related diseases, little is known about the relationship between RA and accelerated aging. To assess the associations between biological aging and the risk of RA, the genetic susceptibility to RA, and the effect of biological aging on the life expectancy of individuals with RA, investigators, led by Li Chen, PhD, from Tongji Medical College at Huazhong University of Science and Technology in Wuhan, China, conducted cross-sectional analyses of 2 observational studies.

“To our knowledge, our study is the first to assess potential interactions between biological ageing and the genetic risk of rheumatoid arthritis,” investigators wrote.

The study included 28,958 participants from the US National Health and Nutrition Examination Survey (NHANES) (January 1,199 to December 31, 2018), and 6.7% had RA. The mean age of participants was 46.7 years and 49.8% were female. For the life expectancy analysis, they excluded participants (25.8%) with missing death information, so the sample only included 21,477.

Participants also came from a UK Biobank, a prospective study with ≥ 500,000 participants. They included 299,651 participants; the mean age was 56.1 years and 53% were female. The life expectancy analysis included 303415 US Biobank participants after excluding 8.7% because they were taking antirheumatics without having rheumatoid arthritis.

The team calculated chronological age-adjusted biological age using the Klemera-Doubal method (KDMAge) and phenotypic age (PhenoAge) to assess biological aging in participants. Participants were considered to have accelerated biological aging if their KDMAge or PhenoAge acceleration values were > 0.

Cross-sectional analyses demonstrated each 1-year increase in age-adjusted biological age was linked to a 1% - 10% increase in the risk of RA. In the NHANES, individuals with accelerated aging had a greater risk for RA than individuals without accelerated aging for KDMAge acceleration (odds ratio [OR], 1.21; 95% CI, 1.03 – 1.42; P = .018) and PhenoAge acceleration (OR, 1.46; 95% CI, 1.26 – 1.69; P < .0001).

Furthermore, in the UK biobank, individuals with accelerated aging had an increased RA risk than individuals without accelerating aging for both KDMAge (OR, 1.96; 95% CI, 1.71 – 2.24) and PhenoAge (OR, 2.71; 95% CI, 2.51 – 2.92). The prospective analyses of US Biobank also showed accelerated biological aging was linked to an increased risk of incident RA by KDMAge (hazard ratio [HR], 1.27; 95% CI, 1.03 – 1.55) and PhenoAge (HR, 1.70; 95% CI, 1.52 – 1.92). Each 1-year increase in accelerated aging increased the risk of incident RA by 5%.

Investigators also found for participants with a high genetic predisposition to RA, accelerated biological aging was linked to an increased risk of incident RA (KDMAge: HR, 1. 48; 95% CI, 1.01 – 2.17); PhenoAge: HR, 2.05; 95% CI, 1.64 – 2.55).

“This finding suggests that efforts targeting anti-ageing, such as senolytic medicine and promotion of healthy lifestyle, should be prioritised in people with high genetic susceptibility to rheumatoid arthritis,” investigators wrote.

Additionally, at 45 years old, people with RA had a reduced life expectancy compared to people without RA. For NHANES participants at age 45, life expectancy was 33.4 years for people with RA (95% CI, 30.9 – 35.9) and 35.1 years for people without RA (95% CI, 32.7 – 27.4). As for the UK biobank participants, life expectancy was 36.6 years for people with RA (95% CI, 35.7 – 27.4) and 39.8 years for people without RA (95% CI, 39.2 – 40.3).

“Our findings suggest that people with rheumatoid arthritis and accelerated biological ageing have an increased mortality risk and lost 2.4 – 5.7 years of life expectancy at the age of 45 years compared with those with rheumatoid arthritis without accelerated biological ageing,” investigators wrote.

A sensitivity analysis demonstrated accelerated biological aging with RA was linked to a greater risk of death (KDMAge: HR, 1.04; 95% CI, 1.00 – 1.08), P = .049; PhenoAge: HR, 1.06, 1.04 –1.07; P < .0001.

Limitations highlighted by the investigators include having unmeasured confounders due to measurement errors which may lead to biased results, data on biological aging only being available at baseline, only having self-reported data on RA, a majority of participants being White, the study being observational which prevents them from determining causal links, they dichotomized the age-adjusted biological age, and lastly the hazard ratios should be viewed with caution since they are based on a single point in time during the follow-up.

“In conclusion, our findings suggest that identification of accelerated biological ageing by use of surrogate measures could be a promising approach in the primary and secondary prevention of rheumatoid arthritis,” investigators wrote.

References

  1. Chen L, Wu B, Mo L, et al. Associations between biological ageing and the risk of, genetic susceptibility to, and life expectancy associated with rheumatoid arthritis: a secondary analysis of two observational studies. Lancet Healthy Longev. 2024;5(1):e45-e55. doi:10.1016/S2666-7568(23)00220-9
  2. How is Lifespan Affected by RA? National Rheumatoid Arthritis Society. https://nras.org.uk/resource/how-is-lifespan-affected-by-ra/#:~:text=Over%20the%20years%2C%20studies%20have,improvement%20of%20quality%20of%20life. Accessed February 13, 2024.


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