Demographic aging is progressing at an unprecedented rate worldwide, driven by extended longevity and reduced birth rates (1). Projections indicate that this demographic shift will substantially elevate the number of individuals requiring care support in coming decades (2). Among aging-related conditions, sarcopenia—a progressive loss of muscle mass and strength—represents a prevalent contributor to care dependency challenges (3). Addressing this condition is critical for enhancing intrinsic capacity (IC), a foundational concept enabling transitions from disease-focused healthcare models to function-oriented frameworks, thereby advancing objectives of healthy aging (4, 5).

Sarcopenia, a degenerative musculoskeletal condition linked to aging, involves the progressive reduction of muscle mass, diminished strength, and impaired physical function (4). As demographic shifts toward older age groups intensify globally, sarcopenia prevalence is increasing steadily, affecting 10–27% of populations across varied geographical contexts (6). Extensive research links this condition to elevated risks of functional impairment, nutritional deficiencies, fall-related injuries, and premature death (7, 8), contributing to escalating societal, individual, and financial pressures projected for future generations (9). Emerging data indicate that structured exercise regimens, nutritional optimization, and activity modifications can markedly enhance muscular integrity, power, and functional capacity (10, 11). Given its high prevalence and associations with both acute and chronic health complications, identifying modifiable risk factors and elucidating mechanisms to mitigate sarcopenia’s development remain critical priorities for public health initiatives.

In pursuit of “healthy aging” objectives, the World Health Organization (WHO) introduced the framework of IC in its 2015 Global Report on Aging and Health. IC represents the composite of an individual’s cognitive and physiological reserves, redirecting geriatric care priorities from pathology management to functional optimization. This capacity typically diminishes with advancing age (12). Empirical studies have established robust correlations between IC deficits and heightened risks of frailty (13), fall-related injuries (14), and premature mortality (15)—outcomes exacerbated by sarcopenia’s progression (16). IC is operationalized through standardized metrics evaluating five interconnected domains: locomotion, cognitive, psychology, sensory acuity (vision and hearing), and vitality (5). Notably, deterioration of IC parameters was associated with an increased risk of sarcopenia (17–22). Scholars advocate that systematic tracking of IC may serve as a predictive indicator for functional decline or negative health events, enabling timely preventative strategies (23). However, gaps persist in understanding the biological pathways linking IC degradation to sarcopenia pathogenesis, warranting deeper mechanistic investigation.

The widespread implementation of existing nutrition assessment tools in clinical practice has been hindered by their complexity. To overcome this limitation, Doi et al. proposed a novel and readily calculable index, termed the Triglycerides (TG), Total Cholesterol (TC), and Body Weight (BW) Index (TCBI) (24).

TCBI represents an innovative nutritional index that synthesizes TG, TC, and BW to offer a comprehensive assessment of metabolic health. Compared with traditional lipid indicators, such as low-density lipoprotein (LDL), high-density lipoprotein (HDL), and the ratio of triglycerides to HDL (TG/HDL), TCBI offers the advantage of integrating lipid profiles with body composition (body weight). It captures the synergistic effects of metabolism and nutrition while simplifying risk stratification through a single composite score.

Empirical evidence indicates that a higher TCBI is correlated with enhanced metabolic health, potentially mitigating cognitive decline in middle-aged and older populations (25). TCBI was also inversely associated with the incidence of stroke and stroke-associated pneumonia (SAP) (26, 27). Furthermore, TCBI can serve as a prognostic indicator for coronary heart disease (24), critical illness requiring mechanical circulatory support (MCS) devices (28), and heart failure (29). Moreover, elevated levels of TG and TC, which constitute components of the TCBI, have been linked to depressive symptoms in midlife (30). Depressive symptoms serve as a psychological indicator associated with IC. The evaluation of IC encompasses vitality, which is measured by the body mass index (BMI) and reflects nutritional status (31). There is a positive correlation between BMI and lipid abnormalities, including increased levels of TG and TC (32). Previous studies suggest that TG, TC, and BW may be inversely related to sarcopenia (33–35). However, the relationship between TCBI and sarcopenia remains ambiguous, necessitating further investigation to elucidate the underlying mechanisms.

This cross-sectional study employed data from the 2015 China Health and Retirement Longitudinal Study (CHARLS), a nationally representative survey, to investigate the associations among IC, TCBI, and sarcopenia in individuals aged 45 years and older. Utilizing a mediation analysis framework, the study sought to evaluate whether TCBI functions as a mediating variable in the pathways linking IC to sarcopenia. The analysis quantified both the total effects of IC on sarcopenia and the indirect effects mediated via TCBI, thereby offering insights into potential mechanistic connections between IC, TCBI, and sarcopenia in middle-aged and older adults.

This study is the first to explore the connection between IC, TCBI, and sarcopenia in middle-aged and older Chinese individuals using 2015 CHARLS data. It found that both IC and TCBI are inversely related to sarcopenia risk, with TCBI mediating the effect of IC deficits on sarcopenia thus supports our original hypothesis.

Biological aging, influenced by inherent mechanisms, leads to decreased IC in sensory, vitality, and psychological areas as people age. This complex process explains the varied functional decline among individuals, affecting more than just physical and cognitive abilities (12). It also includes sensory, vitality, and psychological aspects, which are crucial to IC (49). IC effectively captures the diversity of functional capacity in the older population, regardless of clinical phenotypes (50). Sarcopenia is an age-related condition marked by reduced muscle mass, strength, and physical performance. Managing sarcopenia is crucial for shifting from a disease-centered to a function-centered approach, promoting healthy aging (4, 5). After accounting for confounding factors, a multiple logistic regression analysis showed that each unit increase in IC reduced sarcopenia risk by 15% (OR = 0.85, 95% CI: 0.76–0.95; p = 0.004), indicating IC might protect against sarcopenia.

Research suggests that common risk factors, such as inflammation, may influence both cognitive decline and sarcopenia. In particular, inflammation, which involves cytokines such as Interleukin-1β (IL-1β), is recognized as a contributing factor to age-related cognitive impairments and muscle degeneration (51, 52). Moreover, hormonal changes with aging, like reduced growth hormone and testosterone, affect cognition and muscle health by decreasing protein synthesis and increasing muscle breakdown, leading to sarcopenia. Cognitive decline can worsen hormonal regulation, creating a feedback loop that intensifies both issues (53, 54). Antioxidant nutrients, dietary fats, and B vitamins are crucial for neurocognitive development and may help prevent sarcopenia by enhancing muscle function and minimizing oxidative stress (55).

In alignment with previous research, an elevated risk of impaired IC has been linked to insufficient HGS (56, 57). Sarcopenia, sharing diagnostic criteria with HGS deficiency, is strongly linked to vitality and locomotive capacity in older adults across various groups (58).

Aging, inflammation, oxidative stress, inactivity, and poor nutrition can affect the connection between locomotion and sarcopenia. As people age, muscle fibers, particularly fast-twitch ones, shrink and decline in number, reducing muscle strength and endurance. This diminishes the ability to perform daily tasks and may result in sarcopenia (59, 60). In addition, chronic inflammation, such as Tumor necrosis factor-alpha (TNF-α), leads to muscle catabolism and reduced muscle protein synthesis (61). Moreover, the imbalance between free radicals and antioxidants leads to oxidative stress, worsening muscle degradation and impairing function, which reduces locomotive capacity and raises the risk of sarcopenia (62, 63). Sedentary behavior can cause insulin resistance and muscle weakness, while regular locomotion enhances insulin sensitivity and muscle protein synthesis, mitigating the negative effects on muscle health (64, 65). Adequate protein intake is essential for muscle protein synthesis; insufficient protein can lead to muscle wasting and sarcopenia, especially in older adults. Protein supplementation, particularly with resistance training, may help preserve muscle mass in older adults (66, 67).

Sleep duration and quality as well as dietary intake have been identified as key factors affecting vitality and sarcopenia. Adequate sleep duration and quality may help improve vitality and mitigate the adverse effects of sarcopenia (68, 69). In addition, an adequate intake of energy and protein, particularly from animals and white meat, can help improve vitality and reduce bone loss in older adults, supporting muscle health (70, 71).

Sensory impairments, such as vision and hearing loss, can decrease physical activity by hindering navigation and social engagement. This inactivity is a known risk factor for sarcopenia, as it causes muscle wasting and weakened strength over time (72, 73). Vision and hearing impairment can affect an individual’s ability to prepare and consume a balanced diet, leading to inadequate nutrient intake. Deficiencies in protein and vitamin D, in particular, lead to muscle atrophy and weakness, which are key components of sarcopenia (74, 75).

Hormonal changes linked to depression, like increased cortisol, may contribute to sarcopenia by promoting muscle breakdown and inhibiting growth. Elevated cortisol, a stress hormone with catabolic effects, is often seen in depressed individuals and may lead to muscle degeneration (76, 77). Moreover, elevated inflammatory cytokines like interleukin-6 (IL-6) and TNF-α in depression patients may lead to muscle atrophy and weakness (78, 79).

The link between IC and TCBI in middle-aged and older individuals is intricate. Research conducted in China using an observational design identified an inverse relationship between cognitive decline and the TCBI among adults in midlife and older age groups (25). TG is a key part of TCBI, serving as the body’s main energy reserve. It breaks down into fatty acids and glycerol to fuel the brain, which is crucial for cognitive function, especially in older adults with decreased metabolic efficiency (80). Elevated levels of TC, which are essential for preserving cellular structure and function, have been linked to enhanced cognitive performance (81). Depression as part of the IC assessment of psychology is associated with TG. Depressed individuals often have reduced appetite and weight loss, leading to lower TG levels. Additionally, elevated stress hormones like cortisol in depression can alter lipid metabolism, further decreasing TG levels (82).

Mediation analyses revealed that TCBI partially mediated the association between IC and sarcopenia. Following comprehensive adjustment for covariates, each 1-unit elevation in TCBI corresponded to a 28% decline in sarcopenia risk (OR = 0.72, 95% CI: 0.58–0.90; p = 0.004), underscoring TCBI as a protective indicator of sarcopenia risk. The inverse relationship between TCBI and sarcopenia involves complex physiological mechanisms. TG is a key energy source that suggests sufficient energy reserves for muscle maintenance. Adequate energy levels are crucial for preserving muscle mass, as low energy can cause muscle breakdown and sarcopenia. Therefore, higher TG levels may indicate energy sufficiency, helping to prevent muscle loss (83). Furthermore, TG is essential for producing steroid hormones that are crucial for muscle protein synthesis and repair, helping to maintain muscle mass and prevent sarcopenia (84). Elevated TG levels might suggest improved insulin sensitivity, benefiting muscle health by enhancing glucose uptake, promoting muscle protein synthesis, and lowering sarcopenia risk (85, 86). Furthermore, sufficient TC levels support membrane fluidity and stability, crucial for muscle cell function and repair, helping preserve muscle mass and function in older adults (87). Elevated BMI is frequently linked to higher levels of circulating insulin and other anabolic hormones, which can enhance muscle protein synthesis and inhibit muscle breakdown. This anabolic state may aid in maintaining muscle mass in individuals with higher BMI, thereby explaining the inverse relationship with sarcopenia (88, 89).

In summary, public health strategies should integrate multidimensional IC assessments, including cognitive training, physical activity, and mental health support, into geriatric care. Nutritional interventions to optimize lipid profiles and manage weight through balanced diets and regular monitoring are crucial for improving TCBI. Policymakers should focus on community programs that encourage healthy aging through exercise, nutrition education, and early screenings. By enhancing functional capacity and optimizing metabolic health, we can reduce sarcopenia, ease healthcare burdens, and support healthy aging.

This investigation offers multiple advantages. Foremost, the utilization of longitudinal, population-based cohort data from China enhances the generalizability and empirical robustness of the results. Secondly, this investigation represents the inaugural effort to systematically examine the relationships between IC, TCBI, and sarcopenia risk within middle-aged and older populations. Finally, the potential mediator TCBI was evaluated, which further supports the mechanistic framework and provides a strong rationale for preventing and improving sarcopenia. Concurrently, this study acknowledges several limitations. Firstly, the research’s emphasis on middle-aged and older populations within China’s sociocultural and demographic context limits generalizability of findings to younger cohorts or diverse ethnic/cultural groups. Secondly, the cross-sectional survey design limits causal inference as it measures all variables simultaneously, preventing the establishment of time series and mechanistic pathways between exposures (e.g., IC, TCBI) and sarcopenia outcomes. It cannot determine bidirectional relationships, and TCBI might reflect metabolic adaptations to sarcopenia rather than being causal. Thirdly, unmeasured confounders such as chronic inflammation, physical activity, and dietary patterns could bias the associations and affect the magnitude of the mediating proportion. Fourthly, the exclusion of participants with missing data may have introduced selection bias, potentially limiting the generalizability of the findings. Lastly, this study’s reliance on existing data limited its scope, as it assessed the vitality domain using only BMI instead of the more widely recommended Mini Nutritional Assessment (MNA) scale by the WHO.

To address these limitations, longitudinal cohort studies that track IC, TCBI, and sarcopenia trajectories over time are essential for establishing temporal relationships and elucidating causal pathways. Intervention trials could further investigate whether enhancing IC (e.g., through multimodal exercise programs) or optimizing TCBI (e.g., via lipid-modulating therapies or nutritional interventions) reduces the incidence of sarcopenia. Mechanistic studies incorporating biomarkers (e.g., inflammatory cytokines, hormonal profiles) and advanced imaging techniques (e.g., DXA for muscle mass quantification) would strengthen the biological plausibility of observed associations. Additionally, validating TCBI’s predictive utility across diverse ethnic and clinical populations is critical to confirming its role as a universal nutritional indicator. Finally, integrating multidimensional assessments of vitality (e.g., combining BMI, dietary intake, and inflammatory markers) into IC frameworks could improve their sensitivity in detecting early functional decline. Such efforts would advance personalized strategies for sarcopenia prevention and promote healthy aging.

The research revealed a notable negative association linking IC to sarcopenia, alongside a pronounced negative correlation between TCBI and sarcopenia. Mediation analysis identified TCBI as a partial intermediary in the pathway connecting IC to sarcopenia. These findings hold significant implications for healthcare policy and public health interventions designed to enhance the well-being of middle-aged and older populations affected by sarcopenia, through the assessment of functional and nutritional indicators.