Biopsychosocial Perspectives on Healthy Brain Aging: A Narrative Review

Abstract

The global rise in the elderly population inherently escalates the demand for health and social care. Ensuring cognitive performance for healthy brain aging presents significant challenges for researchers and health professionals promoting self-care behaviors. This article aims to provide a comprehensive and critical analysis of the latest research on healthy brain aging by employing a biopsychosocial framework. It integrates biological, psychological, and social dimensions to elucidate their collective influence on cognitive health in older adults. Methodologically, this article provides a narrative review of the existing literature. A diverse array of bibliographic resources was obtained from prominent electronic databases, including MEDLINE, PubMed, Scopus and Web of Science, to ensure broad coverage of the topic. The search was designed to capture relevant studies published between 2010 and 2025, using key terms such as ‘aging’, ‘biomarker’, ‘neurodegeneration’, and ‘cognitive performance’. Following a rigorous selection process, two field specialists evaluated a total of 106 full-text articles to identify those that met the eligibility criteria, ultimately yielding 70 relevant studies. The findings reveal important connections between psychosocial and biological biomarkers and brain morphology, highlighting lifestyle factors—such as diet, exercise, and social engagement—as crucial for cognitive health. The article also underscores specific biomarkers relevant for assessing brain age and their relationship to neurodegenerative disorders. Notably, while biological markers like Aβ, tau, and α-synuclein (proteins that define the core molecular pathology of common neurodegenerative diseases) are present, they do not guarantee the onset of neurodegenerative diseases; psychosocial factors play an essential role in determining disease manifestation. In conclusion, these results support a holistic approach to healthy aging, which integrates psychosocial environments and lifestyle choices that enhance cognitive resilience. We propose further cross-sectional descriptive studies to better identify the biopsychosocial variables influencing cognitive performance and healthy brain aging, aiming to improve clinical practices and inform public health strategies.

1. Introduction

The phenomenon of population aging represents a critical global challenge that necessitates immediate and sustained attention from policymakers, healthcare systems, and communities at large. The World Health Organization (WHO) predicts that the proportion of individuals aged 65 years and over will rise significantly from 10% in 2022 to approximately 16% by 2050, which presents a myriad of social, economic, and health-related issues that need to be addressed promptly [1]. This demographic transition, while often viewed as a testament to advances in healthcare and better living conditions, also leads to serious implications, particularly in terms of healthcare demands, economic sustainability, and social support systems [2].

Aging is characterized as a gradual process that heightens vulnerabilities to frailty and disease, resulting in cognitive decline, which can ultimately lead to dementia and various neuropsychiatric disorders, including depression and anxiety. Such conditions are particularly prevalent among older adults [3]. In the United States, it is estimated that approximately 10% of the population aged 65 and older is affected by dementia, reflecting a significant public health concern [4]. Despite these challenges, numerous studies have indicated that cognitive decline can be mitigated by early-life modifications of risk factors, suggesting potential avenues for intervention and prevention [5].

Importantly, contemporary biomedical research has primarily focused on the pathophysiology of brain aging. However, these biomedical-only approaches have faced criticism for their insufficient integration of biopsychosocial factors that are essential to a comprehensive understanding of aging [6]. Emerging evidence underscores the need for a more holistic perspective that values the interplay between biological, psychosocial, and lifestyle variables as they relate to cognitive health in older adults [7]. This integrative approach is paramount for developing effective interventions aimed at fostering healthy brain aging.

Epigenetic clocks are a groundbreaking development in our understanding of the biological processes associated with aging. Based on the observation of DNA methylation patterns—the chemical modifications that occur on DNA molecules, influencing gene expression without altering the underlying genetic sequence—these clocks provide a new way of measuring biological age. Methylation develops with age and varies significantly across different brain regions, such as the hippocampus and prefrontal cortex, which exhibit distinct methylation patterns. While measurement of epigenetic age can be conducted through blood or saliva samples, it is important to note that these findings may not directly correlate with changes in brain tissue. This highlights a critical limitation of current measurement techniques and the need for further research using brain tissue samples [8,9].

The role of epigenetic modification in cognitive health and the incidence of neurodegenerative diseases such as Alzheimer’s has attracted attention, particularly in relation to lifestyle factors that can affect both epigenetic age and cognitive reserve. Factors such as musical training and bilingualism are increasingly recognized as significant contributors to enhancing cognitive reserve, thus potentially lowering the risk of dementia [10]. Musical training has been shown to foster neuroplasticity, promoting the structural and functional integrity of brain networks vital for memory and executive functions [10,11]. Similarly, bilingualism has been shown to have protective effects against cognitive decline by enhancing executive control and cognitive flexibility, both of which are crucial during the aging process [8,9,10,11]. Together, these lifestyle factors emphasize the importance of a biopsychosocial approach to fostering cognitive resilience in healthy aging, which aligns well with the proposed model in this review.

Approaches to Brain Aging

The process of brain aging is a complex and multifaceted phenomenon, primarily characterized by significant structural and functional changes in the brain. As individuals age, there is a marked decrease in the volume of both gray and white matter, particularly in regions essential for cognition, motor control, and executive functions [12]. Neurodegenerative biomarkers such as amyloid-beta (Aβ) and tau protein are pivotal in the development of neurodegenerative conditions, particularly Alzheimer’s disease. These markers tend to increase in concentration with age, and their accumulation is associated with the progressive decline in cognitive functions, although this relationship is not linear, complicating their role as predictive indicators of neurodegeneration [13].

This complexity underscores the need to explore the interactions between genetic, environmental, and lifestyle factors that may influence cognitive aging. A deep understanding of these interactions is crucial for developing targeted and personalized interventions aimed at mitigating the effects of aging on long-term cognitive health [14]. For instance, neuroplasticity—the brain’s capacity to adapt, reorganize, and form new neural connections in response to experiences and learning—is viewed as a critical element in fostering cognitive resilience during aging [15]. This adaptability is not only evident in recovery from brain injuries but can also be enhanced through lifelong learning and engagement in stimulating activities, which allow individuals to acquire new skills while maintaining active cognitive engagement [16].

Research indicates that physical exercise, beyond its well-documented physical benefits, promotes neurogenesis, the process of forming new neurons, especially in the hippocampus, an area integral to memory and learning [17]. Similarly, proper nutrition is essential not only for general health but also for regulating neurotrophic factors like BDNF (Brain-Derived Neurotrophic Factor), which support synaptic plasticity and neuronal health [16]. Engaging in cognitively stimulating activities, such as learning new languages or participating in complex games, is linked to the preservation of cognitive functions and improvement in emotional well-being and self-esteem—factors essential for combating cognitive decline [18].

Socio-demographic factors, including age, gender, education level, and geographic location, are closely interlinked and significantly affect the cognitive performance of older adults [19]. These variables highlight the sources of inequalities in care and treatment experienced during the aging process. As individuals age, there is a well-documented trend toward cognitive decline, and studies suggest that this decline can differ substantially between genders, with women exhibiting a higher prevalence of cognitive impairment than men [20]. This discrepancy indicates that socio-economic and cultural contexts significantly influence health and access to resources available to older adults. Additionally, educational attainment emerges as a robust protective factor, as higher levels of education correlate with a reduced risk of cognitive decline, potentially due to enhanced cognitive reserve and neuroplasticity associated with higher education levels [21].

Cultural factors also significantly shape how older individuals perceive and manage the aging process. Research indicates that access to cultural resources and participation in community activities correlate with notable improvements in the quality of life and reductions in the perception of cognitive decline [22]. Engagement in cultural activities fosters a sense of belonging and enhances self-efficacy, which are vital for the emotional well-being of older adults. Social participation not only helps maintain connections within the community but also provides opportunities for lifelong learning and the exchange of experiences. Promoting active aging, where the cultural contributions of older adults are recognized and valued, enhances overall well-being and life satisfaction, both of which are critical for ensuring healthy and dignified aging [23].

The psychosocial approach serves as an essential framework for fostering healthy brain aging. Interventions that promote healthy eating, regular physical activity, and active social participation not only provide physical health benefits but also positively influence cognitive functioning [24]. Sleep quality is another critical factor recognized as vital for cognitive and emotional well-being. Adequate rest is fundamental for memory consolidation and plays a crucial role in emotional regulation, enabling older adults to better manage stress and anxiety [25]. Moreover, a sense of belonging to meaningful communities and social groups correlates with more favorable mental health outcomes. Support networks are instrumental in combating social isolation, a risk factor with detrimental effects comparable to those of smoking [26]. Encouraging participation in group activities and volunteer programs can significantly enhance the quality of life and cognitive resilience among older individuals, fostering a community atmosphere of mutual support vital for successful aging [27].

These insights underscore the necessity for an integrative perspective that considers both biological and psychosocial dimensions of brain aging. It is evident that brain aging is neither a linear nor homogeneous process; rather, a multitude of factors interact to influence cognitive experiences in older adults. By fostering neuroplasticity through healthy lifestyle choices, education, and vibrant social engagement, we can promote healthier and more resilient aging. This highlights the crucial roles of psychosocial interventions and public policies aimed at the comprehensive well-being of older populations [26].

In summary, this review aims to provide a comprehensive and critical analysis of the latest research on healthy brain aging, employing a biopsychosocial framework. This framework integrates biological, psychological and social factors to elucidate their collective influence on cognitive health in older adults. Given the interdisciplinary nature of our review, our goal is to engage a diverse audience, including neuroscientists, gerontologists, psychologists, and public health professionals, in order to gain a better understanding of the intricate relationship between biological and psychosocial factors in healthy brain aging. Ultimately, we aim to promote dialogue and collaboration across different disciplines to enhance research and practice in this critical field of study.

2. Materials and Methods

The article is structured as a narrative review [28], which entails a comprehensive and critical examination of the existing literature on healthy brain aging. This methodological approach allows for the integration of information from diverse sources and clinical experiences. Various bibliographic resources were consulted during the first quarter of 2025, facilitating the selection of relevant studies to present an updated and thorough understanding of the topic. Unlike systematic reviews that aim to compile all relevant studies exhaustively, a narrative review emphasizes the interpretation and contextualization of the considered information [29].

A targeted search was conducted in various electronic databases, including MEDLINE, Web of Science, Scopus, PubMed, ScienceDirect and Latindex. This search was carried out in the first quarter of 2025 to identify relevant articles in this field. The search algorithm used for the different sources included the following terms: ‘Aging’; ‘Biomarker’; ‘Neurodegeneration’ (Title); ‘Functional markers’; ‘Healthy’; ‘Brain aging’ (Title); ‘Biopsychosocial factors’; ‘Brain age’; ‘Cognitive performance’ (Title). Various types of studies were considered, including systematic reviews, meta-analyses, experimental studies, quasi-experimental studies and clinical trials. Articles published in English or Spanish between 2010 and 2025 were included. A wide range of articles from different fields were included, such as neurobiology, neuroscience, psychology, clinical gerontology, medicine and public health.

Two authors specializing in the field reviewed and evaluated a total of 106 full-text articles to determine their relevance and identify any methodological inconsistencies. Of the total articles reviewed, 70 met the eligibility criteria for this review. Bias assessment was controlled using the National Heart, Lung, and Blood Institute tool [30], which allows the rigor of articles to be evaluated and bias to be categorized. For details view flowchart in PRISMA Style (Figure 1).

The criteria for selecting literature have been pivotal in shaping the article’s theoretical framework. Recent studies focused on biological, socio-demographic, and psychosocial elements of brain aging have been included, allowing for an interdisciplinary fusion of knowledge. This inclusion of timely and pertinent scientific literature underscores the importance of exploring multiple dimensions in research concerning aging and cognitive health. The methodology adopts a multidisciplinary perspective, integrating concepts from neuroscience, psychology, gerontology, and education. Such an approach is crucial for comprehending the intricacies of brain aging. By factoring in biological, psychological, and social influences, we can gain a nuanced understanding of the interactions affecting cognitive impairment and healthy aging [28].

Critical Analysis

The article presents a critical analysis that underscores the limitations of traditional approaches focused exclusively on the biology and pathophysiology of aging. It argues that neglecting the psychosocial dimensions restricts a comprehensive understanding of the factors that promote optimal brain health. This critique is supported by literature emphasizing the necessity to broaden the theoretical frameworks guiding research in this area [30].

A pivotal aspect of the methodology is the development of a biopsychosocial model designed not only to describe but also to propose a practical theoretical framework for future research and clinical practice. This model synthesizes findings from various studies, providing health professionals with recommendations on addressing cognitive impairment through education, interventions, and self-care [31,32]. Moreover, the article employs a wide array of empirical sources, including case studies, preceding research, and meta-analyses, to reinforce its claims. This approach elucidates how each component of the biopsychosocial model influences the well-being of older individuals over time [33].

In summary, this article highlights the importance of integrating biological and psychosocial factors to understand the complexity of brain aging. It emphasizes that brain aging is neither a linear nor a uniform process; rather, it is shaped by a multitude of interacting factors. Promoting neuroplasticity through healthy behaviors, education, and active social engagement represents a promising strategy for fostering healthier, more resilient aging. Additionally, it underscores the critical role of psychosocial interventions and public policies in supporting the holistic well-being of older adults [34].

3. Results

The subsequent

Table 1. Association among Psychosocial Biomarkers, Mechanisms of Action, and Morphological Impact in Brain Aging.

Psychosocial Biomarkers	Psychosocial Factor	Mechanism of Action	Morphological Impact	Author(s)
Eating Behavior	Leptin synthesized by adipose tissue elevates Brain-Derived Neurotrophic Factor (BDNF) levels, involved in the formation of new memories related to episodic and semantic memory. Omega-3 fatty acids, flavonoids, and B- vitamins. Gut microbiome and its influence on certain dietary factors are generating promising evidence that promotes healthy brain aging.	Elevates BDNF levels, essential for neuroplasticity and memory formation. Dietary manipulation of the gut microbiota can enhance brain functions during aging. Affect the slowing of brain atrophy (Hippocampus and entorhinal cortex) and generate a lower risk of dementia associated with the APOEε4 genotype.	Affects dendritic morphology of the hippocampus and hypothalamus, positively influencing overall brain plasticity. Protect the brain by improving neuronal integrity and synaptic plasticity, reducing inflammation and damage from beta-amyloid, and improving cerebral blood flow. The gut–brain axis directly influences brain function and mood, based on levels of available serotonin linked to a range of neurodegenerative conditions, including dementia.	O’Malley et al., 2007 [35]. Amadieu et al., 2017 [36]. Flanagan et al., 2020 [37].
Physical Activity	Engaging in moderate and intense physical activity generates earlier and broader neuro-electrical potentials.	Enhances neuronal transmission, improving working memory, attention, and executive control.	Increases white matter (WM) volume in critical regions (e.g., corona radiata, fornix, corpus callosum) with more neuronal connections in the prefrontal cortex, reduces cortical thinning, preserves frontotemporal sulci.	San Martín et al., 2023 [38]; Vecchio et al., 2018 [39].
Quality of Sleep	Adequate restful sleep (7–8 h. per night) leads to positive changes in working memory processes, attention, and cognitive flexibility. Poor sleep quality tends to interfere with memory consolidation and the clearing of brain toxins, such as β-amyloid (protein), that accumulate during wakefulness.	Functional changes are linked to sex steroid-dependent receptor activity in the suprachiasmatic nuclei of the hypothalamus. Homeostatic mechanisms responsible for regulating the elimination of free radicals, cortical electrical activity, synaptic homeostasis, and memory consolidation are altered, regulated by the preoptic area of the hypothalamus based on Acetylcholine (ACh) and Serotonin (5 HT).	Supports improved cognitive functions and emotional stability, associated with increased structural health of relevant brain regions. Poor sleep quality is associated with decreased functional and structural connectivity of different networks, overlapping in the right superior temporal pole, left mid-temporal regions, and left inferior occipital region.	Madrid-Valero et al., 2017 [40]. Amorim et al., 2018 [41].
Social Participation	Pursuing meaningful activities enhances emotional intelligence and cognitive learning.	Activates the ventromedial prefrontal cortex (VMPFC) and limbic system, crucial for social cognition.	Engages multiple brain regions involving impulse control, emotional processing, and overall cognitive flexibility.	Van der Velpen et al., 2022 [42]; Piolatto et al., 2022 [43].
Quality of Life	Strong emotional regulation influences perceived physical health and discomfort. Strictly related to the physiology of brain activity, cognition, emotion, and stress.	Involves activation of brain areas such as the anterior insula and ventrolateral prefrontal cortex (VLPFC). Based on the optimization of Serotonin, improving cerebral blood flow and reducing inflammation and oxidative stress.	Increases functional connectivity and structural integrity in the corpus callosum, corona radiata, and cingulate regions, promoting cognitive health. A higher quality of life related to physical health and overall health perception was associated with increased gray matter volume in the anterior cingulate cortex, medial prefrontal cortex, insular cortex, and precuneus.	Ourry et al., 2021 [44]. Hahm et al., 2019 [45].
Subjective Well-being	A sense of happiness and optimism significantly impacts overall life satisfaction. The association between subjective well-being and the integrity of brain structures is supported by the limbic-thalamic-cortical pathway involved in emotional regulation.	Changes in grey matter (GM) volume of medial temporal lobes, including the parahippocampal gyrus. Favoring the integrity of white matter involved in emotional regulation by communicating the main regions of the brain.	Alters brain structure contributing to emotional regulation and cognitive efficiency. Happiness was correlated with integrity, especially in the internal capsule, corona radiata, posterior thalamic radiation, cingulum, and superior longitudinal fasciculus.	Kong et al., 2015 [46]. Kokubun et al., 2022 [47].
Marital Status	Marital status correlates with cognitive resilience; individuals never married often exhibit poorer brain health. Marriage is generally associated with a reduced risk of cognitive decline and dementia, while being single, divorced, or widowed is linked to a higher risk.	Situational cognitive reserves generated from problem-solving in partnerships enhance cognitive functioning. Marital status is significantly predictive of cognitive decline among older adults, and those with a spouse exhibited better cognitive functioning based on social support received throughout the life cycle.	Participants never married show reduced cortical thickness compared to those living with others, indicating possible protective effects of social bonds. Studies based on mean fractional anisotropy (MFA) demonstrate the integrity of the anterior rostral cingulate cortex, insular cortex, and precuneus in older individuals as measured by gray matter (GM) volume.	Lee et al., 2024 [48]. Zhang et al., 2024 [49].

Abbreviations: BDNF: Brain-Derived Neurotrophic Factor; WM: White Matter; ACh: Acetylcholine; 5 HT: Serotonin; VMPFC: Ventromedial Prefrontal Cortex; VLPFC: Ventrolateral Prefrontal Cortex; GM: Grey Matter; MFA: Mean Fractional Anisotropy.

and

Table 2. Types, Description and Morphological Manifestation of Biological Markers of Brain Aging.

Biological Biomarkers	Type	Description	Morphological Manifestation	Author(s)
Epigenetic Clocks (Current)	Molecular Aging Predictors	Epigenetic clocks assess the molecular alterations that signify the onset of aging at both physiological and phenotypic levels, particularly through analyzing DNA methylation (mDNA) across the human genome.	Specific biological age estimations include DNA methylation assessments in saliva, mitochondrial DNA (mtDNA) analysis in blood, and various measures of mDNA related to plasma proteins.	Higgins-Chen et al., 2021 [50].
Blood Epigenetic Clock	Biomarkers of Cognitive Risks DNAm PhenoAge	This biomarker encompasses one of the well-studied indicators of brain aging and is significantly associated with increased risks for Alzheimer’s disease, cognitive impairments, and dementia. Being a strong predictor of various aging-related outcomes such as physical functioning and Alzheimer’s disease.	Higher epigenetic age correlates with a decrease in brain volumetrics and white matter integrity, as well as an increase in vascular lesions and cortical thinning. An increase in epigenetic markers is associated with heightened activity in pro-inflammatory pathways and interferon, as well as decreased transcriptional activity in response to DNA damage and the subsequent mitochondrial activity.	Hodgson et al., 2017 [51]. Levine et al., 2018 [52].
Epigenetic Brain Clock	Molecular Measure of Brain Aging	This approach offers a direct molecular measurement of brain aging, shedding light on the physiological mechanisms by which aging occurs. This clock enables cellular and mitotic signal assessments related to neuronal attrition with age.	There is a documented link between brain epigenetic age (BAG) and various pathologies, including an accelerated BAG in conditions like bipolar disorder (BD) and Alzheimer’s disease (AD). The lipid elongation enzyme (ELOVL2) hypermethylation serves as a notable age predictor.	Garagnani et al., 2012 [53]; Slieker et al., 2018 [54].
Proteomic Changes	Age-Related Protein Dynamics	Research has identified 1128 age-related proteins that change across various tissues, primarily focusing on plasma proteomics associated with alterations in brain function.	Accelerated proteomic aging is linked to cognitive functions, including reduced executive function, processing speed, visuospatial skills, and overall physical capabilities. Proteins such as beta-2-microglobulin (B2M) and vascular cell adhesion protein 1 (VCAM-1) disproportionately influence neurogenesis and cognitive performance post-age 50.	Smith et al., 2015 [55]; Yousef et al., 2019 [56]; Nikolakopoulou et al., 2019 [57].
Neuroimaging-Based Age Markers	Structural and Functional Imaging Techniques Predictive “brain age” biomarker, using structural neuroimaging.	Structural and functional magnetic resonance imaging (fMRI) is critical in assessing risks associated with mortality, cognitive decline, and diseases such as Alzheimer’s disease (AD). Having a predictive brain image indicating an older-appearing brain is associated with reduced grip strength, lower pulmonary function, decreased fluid intelligence, and higher mortality risk.	Neuroimaging findings can predict transitions from cognitive decline to Alzheimer’s disease more effectively than other measures, suggesting pivotal links between vascular aging and processing velocity. This suggests that neuroimaging data related to epigenetic aging markers provide significant insights into brain health and function.	Cole et al., 2017 [58]. Cole et al., 2018 [59].
Other Types of Biomarkers	Metabolic and Microbiome Markers	Fatty acid metabolism has been identified as a crucial pathway compromised in the context of brain aging, mortality, and Alzheimer’s disease. The human gut microbiome is emerging as an influential biomarker in central nervous system aging.	The plasma metabolome can be employed as a novel predictor of biological aging among humans. The gut microbiome interacts with the central nervous system through various signaling pathways, including those from the enteric nervous system, blood metabolites, and immune responses.	Galkin et al., 2020 [60]; Yang et al., 2025 [61].
Brain Age Gap (BAG)	Age Discrepancy Measurement	The BAG quantifies the difference between an individual’s estimated biological age and their chronological age, offering insights into cognitive health and resilience against aging-related impairments.	Assessing the BAG can provide useful insights into biological aging and potential risks for neurodegenerative diseases, thereby facilitating individualized approaches to cognitive health interventions.	Proskovec et al., 2020 [62].
New study perspectives based on non-invasive biomarkers	Study via Optical Coherence Tomography (OCT) and retinal angiography.	Reliable retinal biomarkers have been demonstrated for non-invasive screening and monitoring of Alzheimer’s disease (AD).	Evidence indicates a relationship between changes in the retina and brain tissue based on a peripapillary reduction in retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), correlating with cognitive function decline and the risk of developing AD.	Koronyo et al., 2023 [63].

Abbreviations: DNA: Deoxyribonucleic Acid; mDNA: Methylation DNA; BAG: Brain Epigenetic Age; BD: Bipolar Disorder; AD: Alzheimer’s Disease; ELOVL2: Lipid Elongation Enzyme; B2M: Beta-2-Microglobulin; VCAM-1: Vascular Cell Adhesion Protein 1; fMRI: Functional Magnetic Resonance Imaging; OCT: Optical Coherence Tomography; RNFL: Retinal Nerve Fiber Layer; GCL: Ganglion Cell Layer.

elucidate the interconnections between various psychosocial factors and biological biomarkers that characterize brain aging. These tables reveal that dietary habits, social contexts, and physical health are foundational elements that influence both the morphology and functionality of the brain during the aging process. By exploring these associations, researchers may design more targeted and efficient interventions aimed at fostering healthy cognitive aging.

Table 1 summarizes the associations among psychosocial factors, their underlying mechanisms, and the morphological impacts on the brain. For instance, eating behaviors are linked to the synthesis of leptin, which elevates brain-derived neurotrophic factor (BDNF), crucial for memory formation and brain plasticity. Emerging evidence indicates the importance of omega-3 fatty acids and gut microbiota manipulation in promoting cognitive health and affecting the slower brain atrophy associated with the APOEε4 genotype. Physical activity is shown to enhance neuronal transmission and increase white matter volume in critical brain regions, thereby improving cognitive performance. Sleep quality emerged as a significant influence on cognitive functioning, with adequate rest positively impacting working memory and emotional stability by regulating key neurobiological processes. Social participation activates brain regions essential for social cognition and impulse control, emphasizing its role in emotional intelligence and cognitive learning. Quality of life and subjective well-being are correlated with increased gray matter volume and improved emotional regulation, highlighting the psychological benefits of strong social connections and active lifestyle choices.

Table 2 provides a detailed classification of biological markers related to brain aging, focusing on their descriptions and morphological implications. Notably, epigenetic clocks are identified as crucial indicators of biological aging, signaling alterations through DNA methylation that reflect physiological aging markers. The Blood Epigenetic Clock demonstrates a strong correlation with cognitive risks and neurodegenerative conditions like Alzheimer’s disease. Molecular measures of brain aging reveal significant links between epigenetic age and various pathologies, including accelerated aging in specific conditions. Neuroimaging-based age markers indicate that older-appearing brain images are predictive of reduced cognitive function and greater mortality risks, reinforcing the value of structural and functional imaging in assessing brain health. Additionally, the exploration of metabolic and microbiome markers reveals emerging pathways through which fatty acid metabolism and gut health can influence cognitive aging. The concept of the Brain Age Gap (BAG) is introduced, summarizing the discrepancies between estimated biological age and chronological age, thereby offering insights into interventions aimed at enhancing cognitive resilience.

Figure 2 serves to visually illustrate the interplay between biological, psychological, and social dimensions that collectively influence cognitive health in older adults. The model highlights various factors including genetic predispositions, epigenetic modifications, and neurobiological changes, reflecting the complexities of cognitive aging. Psychological constructs related to cognitive engagement and emotional health are emphasized, demonstrating their critical roles in mediating biological aging effects. Lastly, social factors underline the significance of community participation and social support in fostering healthy brain aging.

4. Discussion

The findings of this article underscore the intricate nature of healthy brain aging, revealing that it is deeply influenced by a multifaceted interplay of biological, sociocultural, and psychosocial factors. The proposal of a biopsychosocial model serves as a compelling framework for understanding the multiple layers inherent in the aging process. Research indicates that to improve the quality of life for older adults, it is essential to identify predictors that encompass holistic measures, addressing not just the individual’s functional capacities but also their life contexts, relationships, and collective health status [64]. The model advocates for a paradigm shift where aging is viewed not merely through a biomedical lens, focused on the pathology of neurodegenerative diseases, but also through a more integrated lens that appreciates the significance of psychosocial variables, such as lifestyle, education, and social support, which are crucial in maintaining cognitive health [65].

In light of the critical connection between epigenetic factors and cognitive health, it is clear that promoting healthy brain aging requires the integration of lifestyle choices such as musical engagement and bilingualism into relevant frameworks. These lifestyle factors interact to contribute to cognitive reserve, facilitating a greater capacity to cope with neurodegenerative pathology without exhibiting clinical symptoms of cognitive decline [66,67,68]. Instruments that measure epigenetic clocks can provide a deeper understanding of the protective effects of these lifestyle choices by allowing researchers to explore the correlation between altered DNA methylation and enhanced cognitive function or resilience. Given the diverse mechanisms through which musical training and bilingualism can enhance neuroplasticity and cognitive adaptability, future research must examine these connections in more detail. This includes distinguishing how specific epigenetic changes occur in response to these interventions across different brain regions, and their relationship to overall cognitive health [66,67,68]. This further highlights the need for comprehensive public health initiatives that promote the adoption of such enriching activities as preventive measures against cognitive decline in older adults.

An important aspect of understanding cognitive aging is the role of epigenetic clocks, which act as biomarkers that reflect biological aging by measuring changes in DNA methylation that are associated with environmental and lifestyle influences. It is vital to integrate lifestyle choices such as musical engagement and bilingualism into frameworks aimed at promoting healthy brain aging because these factors enhance cognitive reserve, which allows individuals to cope better with neurodegenerative pathology without exhibiting clinical symptoms of cognitive decline [8,9]. As epigenetic modifications are influenced by various lifestyle factors, including physical activity and dietary habits, understanding how they interact can provide insight into how specific lifestyle choices may foster resilience against cognitive decline. For example, studies have demonstrated that alterations in DNA methylation associated with musical training and bilingualism are linked to improved cognitive function, supporting the idea that these enriching activities can positively impact epigenetic status and promote cognitive health during the aging process [9,10,11].

Investigating the specific pathways through which lifestyle factors influence epigenetic clocks could enhance our understanding of cognitive reserve. Studies suggest that these epigenetic alterations may mediate the effects of lifestyle interventions on cognitive resilience, revealing potential preventive measures against dementia [69]. As evidence linking cognitive activities and lifestyle choices to biological age through epigenetic mechanisms grows stronger, the need for public health initiatives advocating the integration of musical training and bilingual education as proactive strategies for enhancing cognitive longevity and reducing dementia incidence among aging populations becomes more pressing. Therefore, addressing epigenetic factors alongside promoting cognitive reserve could lead to more effective interventions aimed at improving the cognitive health of older adults [70].

The Brain Age Gap (BAG) is evaluated using methods that analyse DNA methylation patterns to provide a biological age assessment which may differ from chronological age. Techniques such as methylation array analysis allow researchers to examine DNA methylation levels at different genomic sites, providing insight into cellular aging. Recent studies have highlighted the variability of epigenetic markers in specific brain regions such as the hippocampus and prefrontal cortex. This reveals how age-related changes can manifest differently within cerebral tissues [71]. Notably, variations in epigenetic age are associated with cognitive health outcomes, including neurodegenerative disorders such as Alzheimer’s disease. Longitudinal studies indicate that individuals with a larger BAG tend to experience more significant cognitive decline, suggesting that epigenetic aging may establish crucial thresholds that impact health trajectories in aging populations [72].

Discussions surrounding the BAG enhance our understanding of its implications for cognitive aging within a biopsychosocial framework. By elucidating measurement techniques and connecting them to cognitive health, we can better appreciate the complexities of cognitive aging and the potential for interventions aimed at mitigating the effects of epigenetic aging. This deeper insight lends scientific credibility to our narrative review and fosters informed dialogue across academic and public health domains. Ultimately, our examination of the brain age gap accentuates its biological foundations while highlighting its practical relevance in developing strategies to support healthy aging and cognitive resilience among older adults [71,72,73].

In this framework, cognitive reserve is a vital concept, defined as the brain’s capacity to withstand neurological damage while preserving cognitive function. Experiences such as bilingualism and musical training can enhance cognitive reserve, serving as protective buffers against neurodegenerative processes [8,9]. Engaging in these activities is therefore crucial for maintaining cognitive health as we age, as research indicates that musical engagement and bilingualism improve the brain’s functional networks, fostering resilience against the cognitive decline associated with aging [9,10]. These lifestyle choices emphasize the importance of active social involvement and intellectual stimulation during midlife for better cognitive performance later in life. Incorporating musical training and bilingualism into strategies for healthy brain aging enhances our understanding of the mechanisms of cognitive reserve that are essential for boosting resilience against dementia. Evidence suggests that musical training promotes neural plasticity and is associated with improvements in cognitive functioning, including memory and attention, in older populations [8,9,10,11]. Furthermore, bilingual individuals exhibit enhanced cognitive abilities, such as superior problem-solving skills and greater cognitive flexibility, which may delay the onset of dementia symptoms. Prioritizing these factors in public health initiatives could lead to more effective dementia prevention strategies for aging communities.

4.1. Practical Recommendations/Policy Implications

Emerging evidence articulates that well-being transcends traditional constructs, suggesting it embodies a triad of physical, mental, and social health. For example, active physical engagement is now supported by robust findings illustrating its role in not only promoting cardiovascular health but also in safeguarding cognitive integrity against decline. Research has consistently shown that regular physical activity can induce neuroplastic changes that enhance cognitive function and memory, thereby reinforcing the effectiveness of the biopsychosocial model in connecting health behaviors with cognitive outcomes [14]. This highlights the imperative of fostering active lifestyles as a cornerstone of healthy aging, suggesting that policy measures aimed at promoting physical activity could yield significant benefits in cognitive preservation for older adults.

Neuroplasticity itself emerges as a pivotal concept in the context of resilience during aging. This adaptive capacity of the brain, influenced by continuous education, physical activity, and nutritional adequacy, plays a crucial role in mitigating or even reversing certain aging effects [74]. Furthermore, the previously observed reductions in neurogenesis and neuronal connectivity can be counterbalanced by engaging in cognitively stimulating tasks, such as mastering new skills, which have demonstrated significant efficacy in preserving cognitive functioning throughout the lifespan [75]. Numerous studies have validated that participation in intellectually enriching activities not only helps maintain cognitive performance but can actively enhance it, exemplifying the brain’s adaptability within a supportive learning environment [38,56].

The socio-demographic factors that mold the aging experience also warrant critical examination. Variability in cognitive decline among different demographics underscores the influence of cultural factors and resource accessibility on aging experiences [76]. The association between higher educational attainment and reduced cognitive decline illustrates the importance of public health initiatives that prioritize educational opportunities across the lifespan [1,4,6]. By constructing educational programs that actively involve older adults, we can significantly enhance their cognitive vitality as well as their social integration, challenging the stigma often faced by aging individuals [1,5,6].

Cultural influences play a key role in shaping the experience of aging within communities. Societies that foster cultural activities and strengthen social interactions tend to observe substantial improvements in the quality of life of their aging populations [77]. Engagement in artistic and community-oriented activities not only mitigates the perceived risk of cognitive decline but also nurtures a sense of belonging while enhancing self-efficacy—factors essential for robust mental health [78]. Thus, cultural vitality and opportunities for active community participation represent critical components that should be embedded in strategies aimed at fostering successful aging.

The psychosocial perspective is paramount in addressing healthy brain aging, emphasizing that a synthesis of healthy habits, community involvement, and access to social support can yield remarkable improvements in the cognitive abilities of older adults [52]. Additionally, the quality of sleep, frequently overlooked, is identified as a crucial determinant of cognitive and emotional health, facilitating memory consolidation and sustaining attention [79]. The presence of meaningful social connections is associated with improved mental health outcomes, accentuating the urgency to cultivate supportive environments that can effectively counteract social isolation, which poses risks comparable to those of smoking [52,68].

In summary, this article highlights the necessity for an integrated model that describes healthy aging while also proposing proactive changes in how aging is perceived and managed. The consolidation of findings across various disciplines signifies the need for further research that will inform effective public policies designed to enhance healthy and genuinely inclusive aging. By embracing a collaborative approach involving health research, practical interventions, and policy frameworks, there lies a definitive path forward toward an environment that sees older adults not merely as care recipients but as integral contributors to society, thereby crafting a more inclusive and vibrant future for all citizens.

4.2. Limitations

While the biopsychosocial model offers a robust framework for understanding healthy brain aging, it is important to acknowledge its limitations. Firstly, the model may not be applicable in all cultural contexts. Variations in cultural beliefs about aging, health practices and social structures can affect the interaction of biological, psychological and social factors, potentially limiting the model’s generalisability.

Secondly, data gaps can hinder the efficacy of the biopsychosocial model. Many studies lack comprehensive datasets including relevant psychosocial and biological measures, which can lead to an incomplete understanding of, and misinterpretation of, the relationships involved. Furthermore, there is a risk of oversimplification when applying the model to specific populations, as this can lead to the neglect of the complexities presented by different demographics. For instance, socio-economic factors and access to health resources can significantly impact how individuals experience aging and cognitive decline.

In addition, while the concepts of “neuroplasticity” and “social participation” are integral to our understanding of healthy brain aging, their measurement methods and evidence levels significantly influence our interpretations of the findings. Neuroplasticity is often assessed using various techniques, including functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), which evaluate changes in brain function. Notably, studies indicate that more sophisticated statistical methods, such as multivariate pattern analysis (MVPA), can better capture complex changes in neuroplasticity by taking into account individual variability in brain activation patterns. In contrast, social participation is frequently evaluated through self-report questionnaires and observational metrics that gauge engagement in community activities and interpersonal relationships. However, the reliability and validity of these measures can vary, influencing the level of evidence presented in the literature.

Furthermore, methodological variations across studies can lead to discrepancies in findings. For example, some research may not adequately account for confounding factors, such as socio-economic status or cultural differences, which can skew results regarding the benefits of social participation on cognitive health. The effectiveness of interventions aimed at enhancing neuroplasticity through social engagement may also differ based on specific methodologies employed. As such, future studies should strive for consistency in measurement approaches and include comprehensive data on social and environmental contexts to facilitate more accurate comparisons. By clarifying the measurement methods and acknowledging variations in evidence quality, we can more cautiously interpret the impact of neuroplasticity and social participation on healthy brain aging.

To address these limitations, we recommend conducting culturally sensitive research that accounts for local contexts and variations. Future studies should prioritise the inclusion of diverse populations and robust datasets that reflect the multifaceted nature of aging and cognition. This will enable the biopsychosocial model to be applied more nuancedly, ensuring its relevance across various demographic groups.

5. Conclusions

The insights drawn from the intricate interplay of biological, psychosocial and lifestyle factors presented in this review highlight the importance of taking a comprehensive approach to cognitive health in aging populations. The synthesis highlights the pivotal role of dietary habits, physical activity, sleep quality, social engagement and emotional well-being in maintaining cognitive function and encouraging healthy brain aging. Notably, the findings suggest that enhancing cognitive reserve through these lifestyle factors can mitigate the effects of neurodegenerative processes, thereby reducing the risk of cognitive decline and dementia. This aligns with existing literature pointing to interventions focused on these areas as an essential component of strategies for improving cognitive health in older adults.

Incorporating biological markers, particularly epigenetic clocks, provides a robust framework for assessing individual differences in response to aging and cognitive impairment. Emerging evidence of significant associations between these biomarkers and cognitive outcomes confirms the value of utilising such measures in clinical settings to identify individuals at risk of cognitive decline. The interplay between neurobiological indicators and psychosocial factors, such as the Brain Age Gap (BAG), further illustrates how lifestyle changes can influence both biological aging and cognitive resilience. This reinforces the urgent need for public health initiatives that promote physical health through active living, as well as emotional and social well-being, as integrated paths towards cognitive preservation.

Furthermore, creating environments that promote musical engagement and bilingualism is a promising way to enhance cognitive resilience, as demonstrated by the existing literature. Such practices have been shown to promote neural plasticity and enhance cognitive flexibility, thereby highlighting their significance in maintaining cognitive function. Therefore, multidisciplinary research efforts should focus on implementing and evaluating programmes that leverage these psychosocial factors alongside biological assessments to develop personalised interventions.

In conclusion, advancing research methodologies that address the multifaceted influences on cognitive aging is paramount to informing effective interventions. By acknowledging the complex interplay between biological markers, psychosocial factors and environmental influences, we can create comprehensive frameworks that enhance cognitive health and promote fulfilling lives for aging populations. Ultimately, this integrative approach must drive policy frameworks to ensure a holistic support system for older adults that effectively addresses their diverse needs.