Accelerated Aging in Rheumatic Disease: From Biology to Lifestyle Intervention Save

At ACR 2025, the session “27M02: Nutrition for Rheumatic Disease: Where Aging Biology, Sarcopenia, and Diet Intersect” invited the audience to view rheumatic disease through the lens of biological aging and to consider how nutrition and exercise can serve as integrative lifestyle interventions.

Dr. Brian Andonian (Duke University) began by reframing rheumatoid arthritis (RA) as a model of accelerated aging. The overlap, he explained, is unmistakable: reduced exercise tolerance, increased cardiometabolic risk, frailty, sarcopenia, osteoporosis, and immune senescence. The biological age of many RA patients, measured through molecular signatures such as IgG glycan profiles, exceeds their chronological age (Abstract #0835). Drawing from the updated Hallmarks of Aging framework (Cell, 2023), Dr. Andonian outlined how impaired nutrient sensing, mitochondrial dysfunction, and gut dysbiosis form a shared mechanistic foundation between aging and autoimmunity. These processes disrupt cellular repair, energy balance, and immune regulation, setting the stage for persistent inflammation and functional decline.

The question, he asked, is whether these mechanisms can be changed. Dr. Andonian’s answer was cautiously optimistic. Nutritional and lifestyle interventions, he noted, can act directly on the same biological circuits that drive aging. Caloric restriction and ketogenic diets can rebalance nutrient-sensing pathways such as mTOR and AMPK. High-fiber and fermented foods can restore microbial diversity and reduce systemic inflammation. Diet combined with exercise can improve mitochondrial health. In a 16-week RA lifestyle intervention trial, increases in muscle oxidative capacity and fitness correlated with lower fatigue and inflammation.

To ground this science in clinical reality, Dr. Andonian shared the story of “Patient M,” a 79-year-old woman with seropositive RA, frailty, and multiple comorbidities. At baseline, she had moderate disease activity and poor functional capacity. Following structured lifestyle and nutritional interventions, her fitness, strength, and inflammatory markers improved dramatically. Three years later, she remained in remission on a reduced DMARD regimen, with higher muscle mass and lower inflammatory indices. Her case, Dr. Andonian explained, shows that targeting aging biology may not only reduce inflammation but also restore function and vitality.

Building on this mechanistic foundation, Dr. Joshua Baker (University of Pennsylvania) explored how these biological changes manifest in the body. Muscle, he emphasized, is not just a tissue but a marker of resilience. Inflammation, disuse, and altered energy metabolism combine to drive rheumatoid cachexia, a loss of muscle mass and strength that can occur even in patients with stable weight or normal body mass index. His research shows that roughly one in four RA patients meets criteria for low muscle mass, double the rate seen in the general population. These patients experience greater disability, lower physical function, and higher mortality. Sarcopenia, he added, may emerge insidiously with age, inactivity, or chronic inflammation, creating a vicious cycle in which weakness limits activity and reduced activity fuels further muscle loss.

Dr. Baker cautioned against the false comfort of stable weight, noting that weight cycling and changes in body composition, especially increased visceral fat and reduced lean mass, predict functional decline. Resistance training remains the cornerstone intervention. Randomized trials demonstrate that structured strength training can improve gait speed, balance, and muscle power, while modest protein intake (around 0.8 g/kg) supports these gains. “Pharmacologic control of inflammation is essential,” he concluded, “but preserving muscle requires intentional, sustained movement.”

Dr. Neha Bhanusali (University of Central Florida) closed the session by translating these biological and physical insights into practical clinical care. Lifestyle change, she emphasized, remains one of the most underused tools in rheumatology. Weight loss of even 5 to 10 percent is associated with measurable improvements in disease activity. Mediterranean-style eating patterns rich in omega-3 fatty acids, olive oil, and polyphenols are linked to lower IL-6 and CRP levels and better cardiovascular health. Exercise and sleep hygiene further modulate immune and metabolic aging. Expanding on this concept, the broader framework of integrative medicine offers a useful guide for patient care. It emphasizes a whole-food, plant-predominant diet, regular physical activity, and restorative sleep, while also addressing stress management, avoidance of risky substances such as tobacco and excess alcohol, and the importance of positive social connection. Together, these pillars of lifestyle medicine provide a practical roadmap for targeting both rheumatic disease and the biology of aging. Many academic and clinical resources now exist to help clinicians incorporate these principles safely and effectively alongside pharmacologic therapy.

The message from this session was clear: aging is not an inevitable decline but a process that can be influenced. Nutrition and exercise, grounded in integrative lifestyle principles, are among the most practical and accessible ways to do so. For rheumatology, the goal is no longer only to control inflammation but to help patients like Patient M not just live longer, but age better.