Healthy Aging Research Articles

The role of socioeconomic factors in sex differences in intrinsic capacity among older adults: A cross-sectional study in Taiwan

ObjectivesThe World Health Organization’s Integrated Care for Older People (ICOPE) framework launched in 2019 is used to assess the intrinsic capacity of older individuals. Older women may face greater socioeconomic disadvantages, which can impact their physical and mental well-being. Therefore, we examined sex differences in intrinsic capacity and the influence of socioeconomic status. MethodsWe conducted a cross-sectional study in Tainan, Taiwan, recruiting 1,268 adults aged 60 or older in 2022. The ICOPE screening assessed cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms. Intrinsic capacity scores ranged from 0 to 6 and were categorized as impairment (1 or higher) or no impairment (0). Binary logistic regression models were used to analyze sex differences in intrinsic capacity, adjusting sequentially for demographics, lifestyle, and socioeconomic factors. ResultsThe prevalence of intrinsic capacity impairment was 34 %. Women had significantly higher odds of intrinsic capacity impairment (women vs. men, odds ratio [OR] = 1.39, 95 % CI = 1.10–1.75). After sequentially adjusting for demographic characteristics, lifestyle, and socioeconomic factors, the ORs were 1.46 (95 % CI = 1.12–1.90), 1.69 (95 % CI = 1.23–2.31), and 1.24 (95 % CI = 0.88–1.73), respectively. Stratified analyses showed that higher odds of impairment in women than in men was evident only in the financially dependent group (P for interaction = 0.059). ConclusionsOlder women in Taiwan have poorer intrinsic capacity than men, a disparity largely attributable to women’s lower socioeconomic status. Strategies to promote healthy aging among women from disadvantaged socioeconomic backgrounds may help mitigate this sex difference in intrinsic capacity.

Impact of community-based multidomain preventive health program on healthcare utilisation among elderly persons in Singapore: a propensity score matched and difference-in-differences study

ObjectivesAgeing populations present substantial challenges for healthcare systems. Community-based health worker (CHW) interventions for promoting healthy ageing and preventing/managing non-communicable diseases have gained considerable attention in recent years. This study...

Inequalities in Transitions to Home Care: A Longitudinal Analysis of the Canadian Longitudinal Study on Aging

ObjectivesTo investigate inequalities in transitions to home care across a broad set of demographic and socioeconomic factors in Canadian middle-aged and older adults. DesignLongitudinal, retrospective cohort study. Setting and ParticipantsA total of 51,338 community-dwelling adults aged 45+ years, using national data from the Canadian Longitudinal Study on Aging across 3 timepoints from 2011 to 2021. MethodsWe analyzed transitions in home care use using multistate Markov models, with home care use and nonuse as transient states, and loss to follow-up as a terminal state. We calculated hazard ratios for transitions between states adjusting for factors related to home care need (ie, functional limitations, chronic conditions) within the following equity strata: income, education, immigration history, sex, gender, rurality, racial background, and tangible social support. ResultsAcross all timepoints, 5.4% of non–home care users transitioned to home care by the next timepoint and 33.2% of home care users continued to use home care at the next timepoint. Among non–home care users, identifying as a woman, female, White, completing higher levels of education, having higher income, and having less support available was associated with an increased likelihood of transitioning to home care use. Among home care users, higher income was also associated with a greater likelihood to discontinue using home care compared with lower income users. The association between income and home care use was stronger among female individuals. Conclusions and ImplicationsWe found meaningful differences in home care transitions across several equity strata. Individuals with higher income have greater ability to access to private care, creating inequity in access to home care services. Gendered factors such as income and social support have important associations with home care use. Home care planning and policy must address the unique barriers and disadvantages diverse populations face to ensure equitable use of home care and promote healthy aging.

Enhancing Physical And Cognitive Function In The Elderly Through Combined Exercise: Preliminary Results Of Korean National Healthy Aging Project

Enhancing Physical And Cognitive Function In The Elderly Through Combined Exercise: Preliminary Results Of Korean National Healthy Aging Project

Age Well, Work Well: Relationship of Healthy Aging with Career Commitment and Bridge Employment Intentions among Pre-Retirees

Old age is considered an achievement to complete the milestones of one's life. However, the aging population presents significant economic, social, and health challenges. There is a need to address these challenges by focusing on bridge employment after retirement and considering healthy aging an essential part of later life. This correlational research aims to study the relationship between healthy ageing, career commitment and bridge employment intention among pre-retirees. Sample of 308 older employees (M= 57.79, SD= 1.88) was selected from government educational sector of Lahore, Pakistan by using non probability purposive sampling technique. The measure included Attitudes to Ageing Questionnaire, The Occupational Commitment Scale, and Bridge Employment Intention Scale. Results indicate a significant positive relation of healthy aging with career commitment (r = .27, p< .05) and bridge employment intention (r = .17, p< .05) of pre-retirees. Inversely, employee’s education has significant negative relationship with healthy ageing (r = -.12, p< .05), career commitment (r = -.19, p< .01) and bridge employment intention (r = -.29, p< .01). Further, the mediation analysis through Hayes process macro model 4 revealed that career commitment mediates the relationship between healthy aging and bridge employment intention. The study provides a valuable insight and suggested that the organizations should value experienced employees for institutional growth and implement flexible work arrangements, continuous learning opportunities and health and wellness programs to promote work after retirement.

Inflammaging and Brain Aging.

Progress made by the medical community in increasing lifespans comes with the costs of increasing the incidence and prevalence of age-related diseases, neurodegenerative ones included. Aging is associated with a series of morphological changes at the tissue and cellular levels in the brain, as well as impairments in signaling pathways and gene transcription, which lead to synaptic dysfunction and cognitive decline. Although we are not able to pinpoint the exact differences between healthy aging and neurodegeneration, research increasingly highlights the involvement of neuroinflammation and chronic systemic inflammation (inflammaging) in the development of age-associated impairments via a series of pathogenic cascades, triggered by dysfunctions of the circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender differences in the susceptibility and course of neurodegeneration that appear to be mediated by glial cells emphasize the need for future research in this area and an individualized therapeutic approach. Although rejuvenation research is still in its very early infancy, accumulated knowledge on the various signaling pathways involved in promoting cellular senescence opens the perspective of interfering with these pathways and preventing or delaying senescence.

Effects of Tai Chi on Healthy Aging and Quality of Life in Seniors

Effects of Tai Chi on Healthy Aging and Quality of Life in Seniors

Recommendations for Healthy Lifestyle for Cancer Prevention and Healthy Aging

Recommendations for Healthy Lifestyle for Cancer Prevention and Healthy Aging

Measures of spatial memory, peripheral inflammation and negative emotional state predict social-cognitive skills in healthy aging cats

Aging is a complex, multidimensional process. Normative aging is typically accompanied by declines in several cognitive domains, including memory and social cognition. As aging progresses, the often-overlooked early manifestations of cognitive decline can advance, leading to an inability to adapt to new situations and environments. Potential mechanisms influencing cognitive decline remain elusive, but, among other mechanisms, inflammaging, an age-related increase in the chronic production of pro-inflammatory mediators, and emotional stress are implicated. Cognitive function in cats is under-researched, with no studies on the link between potential risk factors and cognitive signs in aging subjects. Understanding this link is essential as it may facilitate the early identification of cognitive decline and encourage preventative, individualized interventions. We carried out a citizen science study to investigate, for the first time, the relationship between cognitive functions, stress, and the inflammatory markers interleukin (IL)-1β and IL-10 in 44 healthy, privately owned pet cats (7–14 years of age), who underwent standardized testing in their home environment. A task was employed to test spatial memory, requiring the cat to recall the location of a food-baited container. An unsolvable task was used to assess cats' social cognition and cognitive flexibility by measuring how they used referential communication (i.e., gaze alternation between the apparatus and the caregivers) compared to their persistence in trying to obtain food which was out of reach. Generalized linear regression analysis, conducted while adjusting for demographic factors and stress behaviors, revealed: 1) a predictive positive relationship connecting spatial memory and the use of social referencing with the caregiver (more gaze alternation) in the unsolvable task, highlighting the importance of the interplay between cognitive domains in sustaining complex behaviors, and 2) a reduced engagement in social referencing toward caregivers (less gaze alternation) in the presence of higher serum levels of IL-1β in the unsolvable task, especially as cats get older. A cat’s social cognitive performance was also negatively predicted by stress-related behaviors, which is not surprising given that cats are sentient creatures whose everyday behavior is also influenced by emotional states. These findings provide new insights into the crosstalk between different cognitive domains during aging and the potential contributions of emotions and inflammation to cognitive changes in healthy aging cats. Further research using this multidimensional approach will help explore these mechanisms of cognitive aging and potential markers for early detection of cognitive changes in older cats, which is critical for timely interventions.

The Performance and Associated Risks of the Criteria for Sarcopenic Obesity Proposed by the European Association for the Study of Obesity in a Geriatric Population

Background: There is no gold standard definition of sarcopenic obesity (SO). Our objective is to evaluate the benefit of using the new definition proposed by the European Association for the Study of Obesity (EASO) in older people. Methods: Data from the Toledo Study of Healthy Aging, a study based on a cohort of community-dwelling older adults, were used. SO was defined according to the EASO and by a composite of the Foundation for the National Institute of Health (FNIH) for the diagnosis of sarcopenia and the WHO’s criteria for obesity (Body Mass Index, BMI ≥ 30 kg/m2; waist circumference, >88 cm for women and >102 cm for men). Frailty [Frailty Phenotype (FFP) and Frailty Trait Scale-5 (FTS5)] and disability (Katz Index) statuses were assessed at baseline and at the follow-up (median 2.99 years). Mortality at a 5-year follow-up was also assessed. The Logistic and Cox regression models were used to assess the associations. Results: Of the 1559 subjects (age 74.79 ± 5.76 years; 45.54% men), 30.15% (EASO/ESPEN) vs. 16.36% (FNIH) met the SO criteria (Kappa = 0.42). SO was associated with the prevalence of frailty by both the EASO’s [OR(95%CI): FFP: 1.70 (1.33–2.16); FTS-5 binary: 2.29 (1.60–3.27); β(95%CI): FTS-5 continuous 3.63 (3.00–4.27)] and FNIH+WHO’s criteria [OR (95%CI): 2.20 (1.61, 3.00)]. The FNIH + WHO’s criteria were cross-sectionally associated with disability [OR: 1.52 (1.07, 2.16); p-value 0.018], while the EASO’s criteria were not. The EASO’s criteria did not show any association at the follow-up, while the FNIH + WHO’s criteria were associated with incident frailty. Conclusions: The EASO’s new criteria for sarcopenic obesity demonstrate moderate agreement with the traditional definition and are cross-sectionally associated with adverse events, but they do not effectively predict the outcomes generally associated with sarcopenic obesity in older adults. Therefore, the performance of the EASO’s criteria in older people raises the need for refinement before recommending it for generalized use in this population.

The Inflammatory Cytokines in Rheumatoid Arthritis and Their effect in the Progression and Pathogenesis of the Disease

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disorder affected the entire body. Aims of the study: Estimation of levels of inflammatory biomarkers in patients with RA and investigation of their impact on the development and severity of the disease. Methodology: This trial is a case-control one involving 44 patients with RA and 44 healthy age matched controls. Blood samples (5 ml) were collected from each participant, anti-CCP, RF, CRP, and ANA levels were measured using a Cobas device, while TNF-α, IL-10, IL-6 and IL-1β, were determined by an ELISA assay. Result: The results showed no significant variations in age, place of residence, and smoking between the RA and control groups, while there were significant variations in BMI, gender, and professional status. The levels of ESR, anti-CCP, RF, ANA, and CRP were significantly elevated in the RA group (P<0.001 for each) than in the control group. The study of cytokine levels also showed significant variations between the two groups, with an increase in TNF-α, IL-6 and IL-1β, and a decrease in IL-10 in the patients. IL-1β was positively correlated with age, IL-6, IL-10, and TNF-α. Conclusions: The results indicate that cytokines levels such as TNF-α, IL-6, IL-1β, and CRP are elevated in RA patients, reflecting elevated inflammatory activity, while levels of IL-10 are decreased, which may contribute to the exacerbation of the disease.

Lipid profile in elderly and centenarian subjects in Kazakhstan: a case-control study

Introduction. The health of centenarians is a major focus in global studies. Dyslipidemia is directly linked to the risk of cardiovascular diseases, which pose a growing burden on healthcare due to the increasing elderly population. Studying the lipid profiles of centenarians is important for preventing circulatory system diseases and promoting healthy aging. This research aims to compare the prevalence of dyslipidemia in centenarians (median age 96 [95-97]) with elderly individuals (median age was 69 [64 – 74]) in the Republic of Kazakhstan and examine potential predictors of dyslipidemia in the centenarian group. Methods. The study involved 46 centenarians (study group) and 82 elderly individuals (control group). Statistical analysis was used to process the data, including blood markers and demographic variables, to identify factors contributing to dyslipidemia. Results and conclusion. The prevalence of hypercholesterolemia in centenarians was 32.6% (15 people - 3 men; 12 women), with elevated LDL levels in 4.3% (2 women). In the control group, hypercholesterolemia prevalence was 29.3% (24 people - 6 men; 18 women) and elevated triglycerides in 6.1% (3 women; 2 men). The study and control groups were compared based on their lipid profile characteristics, which showed similarities as indicated by all p-values being above 0.05: Cholesterol (p=0.348), HDL (p=0.975), LDL (p=0.161), and Triglycerides (p=0.159). Decreased physical activity was a predictor of dyslipidemia in centenarians. Excessive cholesterol levels were significantly higher among women than men in both groups. The primary factor for dyslipidemia was low physical activity, with other predictors having no significant impact on the lipid profiles of centenarians. This factor should be considered when assessing cardiovascular disease risks and all-cause mortality.

Caenorhabditis elegans as a Model to Study Aging and Photoaging.

Caenorhabditis elegans (C. elegans) has emerged as an outstanding model organism for investigating the aging process due to its shortened lifespan, well-defined genome, and accessibility of potent genetic tools. This review presents the current findings on chronological aging and photoaging in C. elegans, exploring the elaborate molecular pathways that control these processes. The progression of chronological aging is characterized by a gradual deterioration of physiological functions and is influenced by an interaction of genetic and environmental factors, including the insulin/insulin-like signaling (IIS) pathway. In contrast, photoaging is characterized by increased oxidative stress, DNA damage, and activation of stress response pathways induced by UV exposure. Although the genetic mechanisms of chronological aging in C. elegans have been characterized by extensive research, the pathways regulating photoaging are comparatively less well-studied. Here, we provide an overview of the current understanding of aging research, including the crucial genes and genetic pathways involved in the aging and photoaging processes of C. elegans. Understanding the complex interactions between these factors will provide invaluable insights into the molecular mechanisms underlying chronological aging and photoaging and may lead to novel therapeutic approaches and further studies for promoting healthy aging in humans.

The Impact of Flavonoid Supplementation on Serum Oxidative Stress Levels Measured via D-ROMs Test in the General Population: The PREVES-FLAVON Retrospective Observational Study.

Oxidative stress has emerged as a key contributor to numerous NCDs (non-communicable diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy. The study included 32 healthy participants (11 men, 21 women) aged 45-65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin, and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1-2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters. Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin, and hesperidin or a similar product long-term. While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.

Relationship Between Lifestyle Factors and Accelerometery Based Motion Capture Analysis During An Active Stand In Healthy Older Adults

Abstract Background One in three individuals aged over 65 and one in two individuals over 80 experience falls in a year. As the population ages, preventing balance issues and falls among healthy older adults becomes increasingly critical. As the population ages, preventing balance issues and falls among healthy older adults becomes increasingly critical. We hypothesized that individuals may display distinct patterns of micro-movement during this test, undetectable to the naked eye but identifiable using motion capture technology. Methods Participants aged 50 years and older were recruited from a local healthy ageing group. Participants underwent an Active Stand (AS) test, consisting of lying down for 10 minutes followed by standing up as quickly as possible and remaining motionless for 3 minutes. During the test, participants wore an accelerometer Participants underwent an Active Stand (AS) test, consisting of lying down for 10 minutes followed by standing up as quickly as possible and remaining motionless for 3 minutes, during the test, participants wore an accelerometer. Computations were carried out on the signals for all remaining participants. Computations were carried out on the signals for all remaining participants. Results 31 participants were initially recruited, with 26 ultimately included after data quality checks. The mean age was 70.5 ± 5.4 years, with 85% being women A lower BMI was found to be significantly associated with a higher MI values a lower BMI was found to be significantly associated with a higher MI values across all three phases of the active stand test across all three phases of the test. Conclusion These findings underscore the potential role of modifiable lifestyle factors, like maintaining a healthy BMI and avoiding smoking, in mitigating early balance problems in older adults.

Biology of Healthy Aging: Biological Hallmarks of Stress Resistance Related and Unrelated to Longevity in Humans

Stress resistance is highly associated with longer and healthier lifespans in various model organisms, including nematodes, fruit flies, and mice. However, we lack a complete understanding of stress resistance in humans; therefore, we investigated how stress resistance and longevity are interlinked in humans. Using more than 180 databases, we identified 541 human genes associated with stress resistance. The curated gene set is highly enriched with genes involved in the cellular response to stress. The Reactome analysis identified 398 biological pathways, narrowed down to 172 pathways using a medium threshold (p-value < 1 × 10−4). We further summarized these pathways into 14 pathway categories, e.g., cellular response to stimuli/stress, DNA repair, gene expression, and immune system. There were overlapping categories between stress resistance and longevity, including gene expression, signal transduction, immune system, and cellular responses to stimuli/stress. The categories include the PIP3-AKT-FOXO and mTOR pathways, known to specify lifespans in the model systems. They also include the accelerated aging syndrome genes (WRN and HGPS/LMNA), while the genes were also involved in non-overlapped categories. Notably, nuclear pore proteins are enriched among the stress-resistance pathways and overlap with diverse metabolic pathways. This study fills the knowledge gap in humans, suggesting that stress resistance is closely linked to longevity pathways but not entirely identical. While most longevity categories intersect with stress-resistance categories, some do not, particularly those related to cell proliferation and beta-cell development. We also note inconsistencies in pathway terminologies with aging hallmarks reported previously, and propose them to be more unified and integral.

An Evaluation of the Important Aspects of Community Nursing Day Care Services for Older People, a Qualitative Review

Abstract Background Day Care Services can support healthy ageing and help prevent social isolation and loneliness amongst older people. However, there is little evidence about the aspects of Day Care Services that are most important and how it effects their overall health and wellbeing. This survey was developed to evaluate the benefits of Day Care Services from the perspectives of the service user. The aim was to: Methods The qualitative evaluation asked two questions. 7 Day Care Services participated, the survey was given to over 300 people and there was over 50% response rate. The data was analysed using qualitative content analysis to identify themes and opportunities for improvement. Results The participants described every aspect of Day Care Services as very important for them. It supports routine, social activity (“gets me out of the house”) and interaction (“meeting people”), provides meals and appropriate nursing interventions. Staff acted as “familiar faces” that can be approached easily and support their service user’s health and well-being. Overall, the majority of attendees would recommend Day Care Services to other people. Conclusion The findings suggest that all aspects of Day Care Services are important for older people to feel part of a community and have healthcare workers to support them on a regular basis. Day Care Services positively affect service users overall health and wellbeing, in particular the social aspect. This would suggest that Day Care Services play an important role in older people's experience of loneliness or social isolation.

Existing and Emerging Measures of Muscle Strength and Mass in the Assessment of Sarcopenia

Abstract Background Sarcopenia, an accelerated loss of muscle strength and mass is a major driver of adverse health outcomes in older people. The European Working Group on Sarcopenia recommends muscle strength assessment with handgrip strength (HGS) or five chair stands test (5CST) and muscle mass assessment with dual energy X-ray absorptiometry or bioelectrical impedance analysis (BIA). However, these methods can be contraindicated, unavailable or patients can be unable to perform them. We sought to compare the existing measures HGS, 5CST and BIA to emerging measures: quadriceps muscle strength (QMS) and muscle ultrasound. Methods Thirty-one participants from a local healthy ageing group (mean age 71±5 years, 80% female) were recruited to the FRAILMatics Physiological Cohort. Max HGS was assessed using the Jamar Plus+ dynamometer and 5CST timed from a standard height chair. Max QMS was measured with the Actiforce hand-held dynamometer. BIA was performed with the TANITA DC-430 MAP and the Sergi equation used to estimate appendicular skeletal muscle mass (ASMM). Rectus femoris muscle thickness (RFMT), vastus lateralis muscle thickness (VLMT) and anterior thigh muscle thickness (ATMT) measurements were taken using the linear array transducer on the GE Vscan Air point of care ultrasound system. Pearson correlation was used to examine the relationship between measures. Results Strong correlation was seen between max QMS and max HGS (r = 0.73, P <0.001); moderate correlation between RFMT, VLMT, ATMT and ASMM (r = 0.51, P <0.01; r = 0.56, P<0.01; r = 0.40, P <0.05). 5CST was not correlated with any of the measures (P >0.05). Conclusion In the assessment of sarcopenia, QMS and muscle ultrasound could be alternatives to HGS and BIA respectively, especially in cases where the latter are not available or contraindicated. 5CST appears less useful in the assessment of sarcopenia and may be more appropriate as a test of physical performance.

Unraveling the Omega-3 Puzzle: Navigating Challenges and Innovations for Bone Health and Healthy Aging.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs, n-3 PUFAs), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), are essential polyunsaturated fats primarily obtained from fatty fish and plant-based sources. Compelling evidence from preclinical and epidemiological studies consistently suggests beneficial effects of ω-3 PUFAs on bone health and healthy aging processes. However, clinical trials have yielded mixed results, with some failing to replicate these benefits seen in preclinical models. This contraindication is mainly due to challenges such as low bioavailability, potential adverse effects with higher doses, and susceptibility to oxidation of ω-3 fatty acids, hindering their clinical effectiveness. This review comprehensively discusses recent findings from a clinical perspective, along with preclinical and epidemiological studies, emphasizing the role of ω-3 PUFAs in promoting bone health and supporting healthy aging. Additionally, it explores strategies to improve ω-3 PUFA efficacy, including nanoparticle encapsulation and incorporation of specialized pro-resolving mediators (SPM) derived from DHA and EPA, to mitigate oxidation and enhance solubility, thereby improving therapeutic potential. By consolidating evidence from various studies, this review underscores current insights and future directions in leveraging ω-3 PUFAs for therapeutic applications.

Midlife dynamics of white matter architecture in lexical production

We aimed to examine the white matter changes associated with lexical production difficulties, beginning in midlife with increased naming latencies. To delay lexical production decline, middle-aged adults may rely on domain-general and language-specific compensatory mechanisms proposed by the LARA model (Lexical Access and Retrieval in Aging). However, the white matter changes supporting these mechanisms remains largely unknown. Using data from the CAMCAN cohort, we employed an unsupervised and data-driven methodology to examine the relationships between diffusion-weighted imaging and lexical production. Our findings indicate that midlife is marked by alterations in brain structure within distributed dorsal, ventral, and anterior cortico-subcortical networks, marking the onset of lexical production decline around ages 53–54. Middle-aged adults may initially adopt a “semantic strategy” to compensate for lexical production challenges, but this strategy seems compromised later (ages 55–60) as semantic control declines. These insights underscore the interplay between domain-general and language-specific processes in the trajectory of lexical production performance in healthy aging and hint at potential biomarkers for language-related neurodegenerative pathologies.