Biological age (BA) has been proposed as a complementary construct to chronological age (CA) for quantifying interindividual heterogeneity in aging trajectories. Biological aging clocks (BACs) integrate molecular, clinical and multi-omics biomarkers to estimate aging-related phenotypes beyond CA. This narrative review critically examines the biological foundations, statistical methodologies, interpretative challenges and translational applications of BACs. We discuss the mechanistic basis of BACs development within the frameworks of the hallmarks and domains of aging, emphasizing the roles of age-related methylome remodeling, immunosenescence, and chronic low-grade inflammation. BACs are classified into three major generations according to their training objectives: first-generation clocks optimized to predict CA, second-generation clocks designed to estimate morbidity and mortality risk, and third-generation clocks developed to quantify the pace of aging from longitudinal biomarker changes. We also review multi-omics and artificial intelligence-based approaches that aim to capture the multidimensional nature of aging. Important limitations remain regarding biological specificity, causal interpretation, reverse causation, confounding, generalizability and clinical applicability of BACs. Current evidence suggests that BACs represent distinct operationalizations of biological aging instead of interchangeable measures of a single construct. Future advances will require longitudinal, mechanistic and diverse population-based studies to improve interpretability, reproducibility, and translational utility.
C. Fermín-Martínez, S. Garcia-Gonzalez, Elizabeth Garcia L. Castañeda et al.· Revista de investigacion cli...· 0 citations
Background Population aging has increased interest in Intrinsic Capacity (IC), defined as the composite of physical and mental abilities that support healthy aging. Because declines in IC precede disability, IC is a useful framework for characterizing individuals with greater vulnerability in later life. Methods We conducted a cross-sectional analysis of the 2021 Mexican Health and Aging Study, a nationally representative survey of adults aged 50 years and older. IC was assessed across five domains using domain-specific impairment, number of impaired domains, and a continuous latent IC score derived from factor analysis. Ordinal logistic regression models were used to examine associations with sociodemographic characteristics, health conditions, and a Social Vulnerability Index (SVI) constructed using a cumulative deficit approach. Findings The sample included 13,403 adults (mean age 65.9 years [SD 9.8]; 57.3% women). IC impairment was highly prevalent: 67.1% had impairment in two or more domains, whereas only 12.5% had no impaired domains. Lower IC was associated with increasing age (≥80 years: OR 3.31; 95% CI 1.10–10.02) and poorer health, including multimorbidity (OR 2.29; 95% CI 1.44–3.64) and poor self-rated health (OR 1.69; 95% CI 1.24–2.28). Lower IC was further associated with social disadvantage, including lower educational attainment (OR 2.33; 95% CI 1.69–3.22) and food insecurity (OR 1.51; 95% CI 1.06–2.16), with higher social vulnerability associated with lower IC (β −0.46; 95% CI −0.51 to −0.41). Interpretation IC impairment is highly prevalent among Mexican adults aged 50 years and older and is strongly associated with social vulnerability and modifiable health factors, supporting IC as an integrative framework to identify vulnerable individuals and inform intervention strategies.
M. T. López-Teros, Fabiola Yocupicio Medrano, Karla Animas Mijangos et al.· PLoS ONE· 0 citations
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