Longitudinal associations between the hallmarks of aging and body composition: a narrative review

Age-related loss of muscle and bone mass and increased adiposity contribute to frailty, disability, falls, and fractures. The hallmarks of aging framework provide a biological model to investigate mechanisms underlying body composition remodeling. However, whether hallmark-related biomarkers are associated with longitudinal body composition changes remains unclear. We conducted a narrative review of longitudinal human studies examining associations between biomarkers and body composition changes. Eligible studies included adults aged 50 years and older with repeated body composition assessment. We found 50 articles: 3 investigated primary, 20 antagonists, and 24 integrative hallmarks. Body composition was mainly measured using Dual-energy X-ray Absorptiometry. Chronic inflammation emerged as the most commonly investigated hallmark. No study was found for genomic instability, epigenetic alterations, proteostasis, macroautophagy, cellular senescence, stem cell exhaustion, or dysbiosis. Primary hallmarks were underrepresented: telomere length was the only primary hallmark identified, with no consistent association with body composition changes. Among antagonistic hallmarks, deregulated nutrient sensing provided consistent evidence: insulin resistance, hyperinsulinemia, impaired glucose homeostasis, and related indices were associated with adverse muscle and adipose changes. Evidence for mitochondrial dysfunction relied on indirect biomarkers and was more suggestive for adiposity than muscle or bone. Among integrative hallmarks, altered intercellular communication and chronic inflammation were most investigated. Hormonal markers including vitamin D, trace elements, inflammatory indices, and systemic biomarkers showed biomarker-specific, sex-specific, and compartment-specific associations. Evidence remains limited and heterogeneous. Current findings support insulin-related nutrient sensing in adverse muscle and adipose remodeling. Studies combining repeated biomarker assessment with precise phenotyping are needed.