Virtual Nature, Metaverse, and NAD⁺: A Narrative Review for Health Planning and Healthy Ageing

ABSTRACT

Background and Aims

Digital experiences—including virtual reality (VR), the metaverse, and exergaming—shape stress, mental health, and physical activity. While nature‐related and urban digital experiences influence health behaviors through different pathways, their impact on nicotinamide adenine dinucleotide (NAD⁺), a key mediator of cellular ageing, remains unclear. This review aims to synthesize evidence and construct a conceptual framework linking these domains.

Methods

We conducted a scoping narrative review synthesizing systematic reviews, meta‐analyses, randomized trials, and observational studies. Approximately 50 key publications were identified through database searches and purposively selected to represent major evidence domains and mechanisms linking VR, stress, physical activity, and NAD⁺ metabolism.

Results

VR nature and digital nature reduce stress, anxiety, and physiological stress markers such as cortisol. In contrast, metaverse environments may enhance positive affect and social connectedness but are also associated with sedentary behavior and potential social fatigue. Immersive VR exercise (exergaming) generates moderate‐to‐vigorous physical activity comparable to traditional exercise and may enhance NAD⁺ metabolism via NAMPT activation. However, no human study has yet simultaneously assessed VR interventions and blood NAD⁺ levels.

Conclusion

We propose a conceptual model linking digital experiences to NAD⁺ metabolism via stress, physical activity, and sleep. This framework highlights a key scientific gap and provides a foundation for future research and health planning.

1. Introduction

A substantial body of research has established that exposure to real natural environments contributes to stress reduction, physiological restoration, and emotional stability. Beyond real nature, randomized controlled trials (RCTs) and systematic reviews have demonstrated that VR nature and digital nature—digital or immersive representations of natural environments—can reproduce similar restorative effects [1, 2]. Additional RCT and controlled evidence supports the same overall conclusion [3, 4]. Systematic reviews have likewise reported restorative benefits associated with VR nature and digital nature exposures [5, 6]. Additional studies reinforce the consistency of these findings across the growing evidence base [7, 8]. Related studies continue to extend this evidence across different contexts and populations [9, 10]. Taken together, the literature indicates that VR nature and digital nature can reproduce similar restorative effects [11, 12]. This overall pattern is also supported by additional work [13]. Short sessions of VR forest exposure have been shown to reduce anxiety, depressive symptoms, emotional load, and cortisol levels, suggesting that VR nature may serve as a practical substitute for real nature when access is limited [5, 9, 12].

Conversely, urban and indoor digital experiences such as the metaverse can enhance immersion, self‐expression, and social interaction—factors associated with improved well‐being [14, 15]. At the same time, these experiences may also lead to increased sedentary behavior. They may also be associated with heightened stress reactivity in certain social contexts [16]. Sleep disturbances and stress‐related problems have also been reported in relation to excessive digital engagement and intensive e‐gaming [16, 49, 50]. Addiction tendencies have likewise been discussed [19].

From a health planning perspective, these technologies are therefore both a potential health resource and a potential health risk. In parallel, research in health and ageing science has increasingly focused on nicotinamide adenine dinucleotide (NAD⁺) as a key molecule involved in energy metabolism, mitochondrial function, DNA repair, sirtuin activation, and the regulation of cellular ageing [20, 21, 22]. NAD⁺ levels are strongly influenced by lifestyle factors such as psychological stress, physical activity, and sleep quality. Since digital experiences directly modulate these very factors, they likely have downstream effects on NAD⁺ metabolism. However, this link has not been systematically explored.

Based on these considerations, this review synthesizes evidence on: (1) the effects of VR nature on stress, emotion, and recovery; (2) the psychological and physical impacts of urban VR and the metaverse; (3) behavioral changes induced by VR‐based exercise (exergaming); and (4) the integration of NAD⁺ metabolism, ageing biology, and lifestyle factors. Ultimately, the aim is not only to describe technological developments but also to propose an integrated conceptual model of digital‐era health behaviors and cellular ageing, providing a foundation for future research, policy design, and health technology assessments.

To facilitate understanding of the proposed framework, an integrative conceptual model is presented in Figure 1.

Figure 1.

Conceptual model linking VR nature, metaverse, and exergaming to NAD⁺ metabolism and healthy ageing.

2. Methods

This study was designed as a narrative review using a scoping approach. The overall aim of the literature review was to map and integrate evidence on virtual reality (VR), metaverse platforms, exergaming, nature exposure, stress, physical activity, nicotinamide adenine dinucleotide (NAD⁺) metabolism, and ageing, rather than to produce pooled quantitative effect estimates.

We searched PubMed and Web of Science for English‐language studies using combinations of terms related to VR, metaverse platforms, exergaming, nature exposure, psychological stress, physical activity, NAD⁺ metabolism, and ageing. We prioritized systematic reviews, meta‐analyses, randomized controlled trials, observational studies, and relevant conceptual or policy papers. Database searches were supplemented by targeted web searches and citation snowballing to identify additional relevant work. From this body of literature, approximately 50 key publications were purposively selected to illustrate major trends, mechanisms, and research gaps.

2.1. The Search Strategy Included Combinations of the Following Boolean Terms

(“virtual reality” OR “VR” OR “metaverse” OR “exergaming”)

AND (“nature exposure” OR “digital nature”)

AND (“stress” OR “cortisol” OR “mental health”)

AND (“physical activity” OR “exercise”)

AND (“NAD + “ OR “nicotinamide adenine dinucleotide” OR “aging”).

2.2. Searches Were Conducted in PubMed and Web of Science

The detailed list of included studies is provided in Supporting Information S1: Table S1.

Given the heterogeneity of study designs, populations, and outcome measures, findings were synthesized narratively rather than quantitatively pooled in a meta‐analysis. Evidence from the selected publications was organized thematically across the main domains of interest (VR nature and digital nature, metaverse and VR‐based mental health interventions, immersive VR exercise and exergaming, and NAD⁺ metabolism and ageing). These themes were then used to structure the results and to inform the development of an integrative conceptual model linking digital experiences, stress regulation, physical activity, and NAD⁺‐related ageing pathways.

As this work is a literature‐based narrative review, no human participants were recruited and no primary data were collected. Instead, the “participants” informing this review are the populations studied in the included articles, such as students, community‐dwelling adults, older adults, and clinical populations. Insights from these diverse study samples guided the scope of the discussion and the formulation of key questions for future research and policy, effectively serving as an implicit discussion guide for interpreting the reviewed evidence.

The scope of this review and the main thematic domains were pre‐specified as follows: (1) VR nature and digital nature, (2) metaverse and VR‐based mental health interventions, (3) immersive VR exercise/exergaming, and (4) NAD⁺ metabolism and ageing. The synthesis of mechanistic linkages across these domains was exploratory and was used to develop the conceptual framework. No subgroup analyses, meta‐analysis, or inferential statistical testing were performed. Therefore, no a priori significance threshold or specification of 1‐ or 2‐sided testing was applicable. Reference management and manuscript preparation were performed using Zotero.

As this manuscript is a narrative review and conceptual framework rather than a clinical trial report, CONSORT items are not directly applicable; however, the review was revised to improve transparency and reproducibility of reporting.

Because this study is a narrative review with a scoping approach, no new statistical analyses or pooled quantitative estimates were performed. Clinical and statistical findings from included studies were reported descriptively, with attention to transparent interpretation of effect direction, study design, and methodological limitations.

Because this study is a narrative review, no new statistical hypothesis testing was performed. Findings from included studies were interpreted descriptively, with emphasis on the direction, magnitude, and consistency of reported effects rather than reliance on p values alone.

Ethics and consent Ethical approval was not required for this study because it is a literature‐based narrative review using previously published sources only and involving no human participants or primary data collection. Accordingly, informed consent was not applicable.

All references were checked for retraction and correction status using PubMed and reference management tools (Zotero). No retracted articles were identified among the cited studies, and any relevant corrections were reviewed and did not affect the interpretation of the cited evidence.

3. Results and Discussion

3.1. VR Nature and Digital Nature

Young adults frequently experience substantial academic and interpersonal stress, creating demand for brief, accessible stress‐reduction interventions within schools, universities, and workplaces. A growing body of evidence indicates that short VR‐based nature sessions can reduce stress‐related outcomes in this population. In a longitudinal RCT among university students, Browning et al. demonstrated that daily 5–10‐min exposure to VR nature reduced symptoms of anxiety and worry compared with control conditions [1]. Similarly, Owens et al. reported that even a single brief session of VR nature improved positive affect and reduced negative mood, supporting the feasibility of VR nature as a rapid, low‐burden intervention [5]. Chan et al. showed that immersive VR forest environments simultaneously improved subjective stress ratings and physiological indicators such as heart rate, suggesting coherent psychophysiological recovery [9]. Meta‐analytic and systematic review evidence from Hubbard et al. and Brambilla et al. further indicates that VR nature interventions consistently: (1) reduce anxiety and depressive symptoms, (2) increase nature connectedness, and (3) promote psychological restoration in non‐clinical samples [2, 4, 13]. Taken together, these findings support the emerging concept of “virtual nature prescriptions” as a potentially scalable mental‐health support tool for young adults, particularly in settings with limited access to real nature.

Digital nature, defined as natural scenes delivered via conventional displays or lightweight VR, represents a lower‐cost and less technically demanding alternative to fully immersive VR. Evidence suggests that such stimuli can improve psychological well‐being and perceived social connectedness, with particular relevance for socially isolated groups. van Houwelingen‐Snippe et al. reported that viewing online nature videos reduced loneliness and increased social connectedness among adults, implying that nature content can serve as a low‐threshold social resource in digital environments [8]. Skibins et al. similarly found that digital nature exposure was associated with improved subjective well‐being and overall quality of life [23]. Among older adults, studies of immersive VR forests and digital nature programmes have reported improvements in cognitive functioning, emotional stability, and social well‐being [24, 25]. These results highlight digital nature as a promising tool for older individuals with mobility limitations or restricted access to green spaces, and suggest potential integration into long‐term care, community‐based elder services, and tele‐rehabilitation. Given that the definition of “digital nature” has not been fully standardized across studies, the term “Digical Nature” may serve as a complementary label to describe the integration of digital and physical dimensions of nature‐related experiences in health contexts, as a terminological clarification and a potential direction for future conceptual clarification.

Studies directly comparing nature‐based and urban/indoor environments provide additional insight into the relative benefits of VR nature. Fan and Baharum synthesized evidence comparing digital nature and actual nature and reported broadly comparable stress‐reduction effects across modalities [3]. Nevertheless, VR nature alone produced substantial reductions in perceived stress, indicating meaningful restorative potential even without physical exposure to green spaces. Reese et al. showed that VR environments containing human‐made structures (e.g., built features within natural scenes) retained substantial restorative value, suggesting that nature‐themed VR may be useful even in highly urbanized or office‐based contexts [12]. Further, Mucha et al. reported that virtual walks in green spaces affected pain perception compared with urban spaces [26], and Wen et al. synthesized evidence on immersive virtual natural settings and patient‐related outcomes [28]. In clinical settings, Chin et al. found that VR nature experiences may be beneficial for patients with cancer, reinforcing VR‐based nature interventions as a feasible adjunct to supportive care [32].

Beyond subjective outcomes, VR nature appears to induce measurable changes in physiological stress markers. Experimental work by Suseno et al. has shown that simulated natural environments presented in VR can modulate heart rate, cortisol levels, and electrodermal activity, indicating that VR stimuli can function both as stressors and as recovery cues depending on design and context [29]. Complementary evidence from real‐world natural environments demonstrates that nature walks reduce salivary cortisol and improve heart‐rate variability (HRV), as reported by Aras et al. [30]. Although direct evidence on VR nature and NAD⁺ metabolism is lacking, these physiological pathways—particularly reductions in cortisol and improvements in autonomic balance—are plausible upstream determinants of inflammation and cellular metabolic processes relevant to healthy ageing.

From an HTA perspective, VR nature and digital nature exhibit several favorable characteristics for integration into health systems and workplace health programmes. Regarding effectiveness, multiple RCTs indicate that VR nature can reduce stress and improve mood in student and young‐adult populations [1, 5]. Additional controlled trials report similar benefits using nature‐based VR relaxation protocols [6, 7]. Systematic reviews and meta‐analyses likewise conclude that VR nature and related digital nature exposures are associated with improvements in stress‐ and mood‐related outcomes [2, 13]. Reviews focusing on stress responses report consistent restorative trends following virtual nature interventions [10]. Additional experimental studies also report reductions in stress‐related outcomes following immersive digital nature exposure [31]. Evidence extends to older adults, supporting relevance for healthy ageing contexts [24, 25]. Clinical and rehabilitation studies further support feasibility and potential benefits of VR nature interventions in patient populations [28, 32]. In terms of safety, these interventions are non‐invasive, and adverse effects are generally limited to transient cybersickness in a minority of users.

A comparative summary of health impacts across different digital and virtual experiences is provided in Table 1.

Table 1.

Comparative health impact profile of digital and virtual experiences (with supporting references).

Category	Nature VR/Digital nature	Urban/General VR	Metaverse	Immersive VR exercise (Exergaming)
Primary purpose/characteristics	Restoration through natural stimuli [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 23, 24, 25, 26, 28, 31, 32]	Immersion and experiential learning [3, 12]	Social interaction and presence [14, 15, 27, 33, 34, 35, 36, 37, 38, 39]	Enjoyment‐driven exercise and movement [40, 41, 42, 43, 44, 45]
Psychological effects	↓ Anxiety, ↓ depression, ↑ mood [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 23, 24, 25, 26, 28, 31, 32]	↑ Immersion and presence [12]	Ambivalent (benefits and overload) [14, 15, 33, 34, 35, 36]	↓ Stress, ↑ positive affect [40, 44, 45]
Social effects	↑ Connectedness and social well‐being [8, 23, 24, 25]	Moderate social engagement	↑ Social presence and self‐expression [14, 27, 37]	Cooperative and group play possible [40, 41, 42, 43, 44, 45]
Physiological effects	↑ HRV, ↓ cortisol [5, 12, 26, 30]	Generally light physiological load	Predominantly sedentary	Achieves MVPA, ↑ heart rate and metabolic demand [40, 41, 42, 43, 44, 45]
Health risks	Low risk, mainly cybersickness [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 23, 24, 25, 26, 28, 31, 32]	Cybersickness and visual fatigue	Dependency, fatigue, potential overuse [36]	Fatigue with excessive use; generally low risk [40, 41, 42, 43, 44, 45]
Theoretical link to NAD⁺	↓ Stress → potential preservation of NAD⁺ via reduced HPA activation and inflammation [29, 30]	Largely neutral	↑ Stress → potential ↑ NAD⁺ consumption via stress‐related pathways [20, 21, 22, 46]	Exercise → ↑ NAMPT → ↑ NAD⁺ metabolism [47, 48]
HTA/policy value	Low‐cost, scalable intervention in healthcare and eldercare settings [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 23, 24, 25, 26, 28, 31, 32]	Useful for education and training	Potential platform for youth mental‐health interventions [14, 15, 27, 33, 34, 35, 36, 37, 38, 39]	Highly promising for preventive medicine and occupational health promotion [40, 41, 42, 43, 44, 45]

3.2. The Metaverse and Mental Health

Existing literature consistently demonstrates that the metaverse exerts ambivalent effects, providing both psychological benefits and potential risks. On the positive side, a systematic review by Aboul‐Yazeed et al. reports that metaverse environments can enhance immersion, increase enjoyment and self‐efficacy, and strengthen social connectedness [14]. These factors collectively contribute to short‐term psychological recovery, particularly in stress‐inducing contexts. Similarly, Buragohain et al. found that metaverse‐based digital therapies show promising preliminary effects, including reductions in anxiety and depressive symptoms, improvements in self‐care behaviors, and enhanced adherence to therapeutic programmes [15].

However, several studies highlight risks associated with excessive or unstructured use. Reported concerns include over‐immersion, social fatigue, dependency tendencies, and increased exposure to harassment, particularly among women and younger users [15, 36]. Del Hoyo et al. argue that the metaverse may function simultaneously as a supportive environment and as a new source of psychological stress [36]. Cerasa et al. emphasize that most metaverse‐related mental‐health studies remain preliminary, with insufficient evidence quality and major uncertainties regarding long‐term impacts [34, 35]. Overall, the current evidence base portrays the metaverse as a technology with both therapeutic potential and significant risk, underscoring the need for structured governance and careful targeting of interventions.

Several authors have proposed conceptualizing the metaverse as a therapeutic space in which psychological interventions can be safely and flexibly delivered. Riches et al. suggest that metaverse‐based therapeutic environments may support emotional regulation and social‐skills training because they offer enhanced controllability, a heightened sense of safety, and the possibility to maintain appropriate interpersonal distance within immersive environments [37]. Such features may be particularly useful for individuals who find face‐to‐face interactions overwhelming. Beyond specialized mental‐health care, Bonneterre et al. and Carroll et al. document growing interest in VR‐based applications for cognitive stimulation among older adults, general health promotion and primary prevention, and frailty prevention [38, 39]. These interventions illustrate how immersive technologies can be positioned upstream in the prevention continuum, rather than solely as treatment tools.

Tabassum et al. propose integrating AI‐driven emotion estimation and behavioral prediction into extended‐reality (XR) environments [27]. This approach could enable personalized psychological support, autonomous monitoring of mental‐health indicators, and adaptive adjustment of therapeutic protocols. From a health‐planning perspective, such systems may contribute to more scalable and tailored mental‐health services, provided that ethical and data‐governance issues are adequately addressed.

The health risks associated with metaverse use can be broadly categorized into three domains. First, high immersion can amplify both sensory and emotional stimulation. Social comparison and gamification elements may elevate arousal and increase psychological load, contributing to cognitive and physiological overload. Second, many metaverse activities are predominantly sedentary. Prolonged use has been associated with sleep disturbances [49, 50]. It has also been associated with chronic fatigue [16, 17]. Third, online harassment and interpersonal stress represent important psychosocial risks. Del Hoyo et al. report that younger and female users are at heightened risk of experiencing harassment, which is associated with increased emotional distress and may exacerbate pre‐existing mental‐health vulnerabilities [36]. These risk domains highlight the need for preventive guidelines, usage monitoring, and integration of supportive services when metaverse‐based tools are deployed in health and educational systems.

3.3. Immersive VR Exercise (Exergaming)

Physical activity plays a critical role in alleviating psychological stress, promoting physical and mental health, and preventing lifestyle‐related diseases. However, global trends in urbanization and digitalization have contributed to a marked decline in physical activity across all age groups, accompanied by increasing sedentary time, which is now recognized as a major public health concern. In this context, immersive virtual reality (VR) exercise and exergaming have emerged as promising digital health technologies that may help establish and maintain sustainable exercise habits. This section synthesizes evidence from systematic reviews and primary studies on immersive VR exercise, focusing on its contributions to physical activity, stress reduction, and psychological well‐being, and evaluates its potential within the frameworks of health planning and health technology assessment (HTA).

Giakoni‐Ramírez et al. demonstrated that immersive VR games can induce physical workloads comparable to traditional exercise, with many young participants achieving moderate‐to‐vigorous physical activity (MVPA) levels [40]. Activities that would normally involve only low‐intensity movement in non‐immersive formats elicited meaningful increases in heart rate when experienced in immersive VR settings, indicating a shift towards physiologically significant exertion. Similarly, Kim et al. reported that immersive VR exercise using head‐mounted displays (HMDs) was associated with increased physical activity levels, elevated heart rate and energy expenditure, and enhanced exercise adherence via motivational engagement [41]. These characteristics make VR‐based exercise particularly attractive for individuals who struggle to initiate or maintain conventional exercise routines.

Mocco et al. found that popular VR exergames such as Beat Saber elicited heart‐rate responses equivalent to those observed during moderate‐intensity aerobic exercise, comparable ratings of perceived exertion (RPE), and higher levels of hedonic motivation [42]. These findings support the view that VR games can serve as legitimate forms of exercise rather than solely entertainment. Rubio‐Arias et al. further reported that immersive VR exercise can match or surpass treadmill exercise in terms of heart rate, oxygen consumption, and momentary psychological arousal [43]. Barbour et al. noted that immersive environments enhance positive affect during exercise, thereby amplifying stress‐relief effects and promoting long‐term adherence [44]. Harrington et al. similarly found that immersive VR exergames evoke physiological responses equivalent to traditional cardiorespiratory exercise while providing superior enjoyment and motivation [45].

Beyond increasing physical activity, immersive VR exercise has been shown to reduce stress and improve emotional well‐being. Giakoni‐Ramírez et al. observed increases in post‐exercise relaxation and reductions in psychological fatigue, suggesting that the immersive quality of VR may augment exercise‐induced stress reduction [40]. Barbour et al. reported that VR exercise induces positive affect and reduces perceived fatigue and resistance towards exercise [44]. This pleasurable engagement is particularly valuable for individuals experiencing high psychological stress or low intrinsic motivation for traditional exercise, as it lowers the psychological barrier to participation and facilitates sustained engagement in physical activity.

Immersive VR exercise holds particular promise for older adults and individuals with physical limitations. VR allows for adjustable exercise intensity, precise environmental control, and substantially reduced fall risk compared with many real‐world activities. Studies have reported improvements in balance, muscle strength, cognitive functioning, and depressive symptoms among older or mobility‐limited users engaging in VR‐based exercise. Combined with the stress‐reducing properties of VR nature exposure described earlier, immersive VR exercise may contribute to a comprehensive well‐being strategy for older adults, simultaneously enhancing physical activity, emotional stability, and social connection.

From an HTA perspective, immersive VR exercise offers several advantages. In terms of effectiveness, randomized and experimental studies show that immersive VR exercise increases physical activity and physiological engagement compared with control or conventional exercise conditions [40, 41, 42]. Additional research has reported improvements in enjoyment and long‐term adherence when exercise is delivered in immersive VR formats [43, 44, 45]. With respect to cost, declining prices of VR hardware are improving feasibility for implementation in schools, workplaces, and healthcare facilities. In equity terms, VR exercise can compensate for environmental or physical barriers to exercise, including urban constraints, mobility limitations, and social or economic health inequities. Safety profiles are generally favorable, with low fall risk and controllable environments increasing suitability for older adults and other vulnerable populations. Acceptability appears high across age groups, including individuals resistant to traditional forms of exercise. Taken together, these features position immersive VR exercise as a clinically and socially meaningful tool for addressing sedentary lifestyles and stress‐related health disparities. Immersive VR exercise and exergaming can induce moderate‐to‐vigorous physical activity, enhance positive affect, and contribute to stress reduction while remaining applicable to older or mobility‐limited populations and performing well across cost, safety, and equity dimensions.

3.4. NAD⁺ Metabolism and Ageing

Nicotinamide adenine dinucleotide (NAD⁺) is a central metabolic molecule involved in energy production, mitochondrial function, DNA repair, and cellular stress responses. Low NAD⁺ levels have been implicated in “inflammaging”, metabolic dysfunction, cardiovascular disease, and neurodegeneration, positioning NAD⁺ as a key regulator of biological ageing [20, 21, 22]. This section synthesizes NAD⁺ research in relation to exercise, stress, and lifestyle factors, and proposes theoretical pathways linking NAD⁺ metabolism with VR nature, the metaverse, and VR exercise.

NAD⁺ participates in redox reactions, sirtuin activation (e.g., SIRT1, SIRT3), poly‐(ADP‐ribose) polymerase (PARP)‐mediated DNA repair, and mitochondrial quality control. Age‐related NAD⁺ decline disrupts these processes, impairing cellular homeostasis and accelerating ageing [20]. Chu et al. documented impaired NAD⁺ metabolism across chronic conditions such as obesity and diabetes, while Abdellatif et al. showed that NAD⁺ depletion contributes to cardiac remodeling and elevated oxidative stress [21, 22]. Collectively, these findings identify NAD⁺ as a critical metabolic hub in ageing biology.

Martens et al. demonstrated that nicotinamide riboside (NR) supplementation raises NAD⁺ levels in middle‐aged and older adults; however, improvements in physical or functional outcomes were limited [51]. Jensen et al. reported that nicotinamide riboside and pterostilbene supplementation did not clearly improve muscle recovery or regeneration after experimental muscle injury in elderly individuals [52]. These mixed results contrast with the robust effects of exercise training. A growing body of evidence indicates that exercise and NAD⁺‐related interventions, including nicotinamide riboside and mononucleotide, contribute to skeletal muscle adaptation and metabolic regulation [52, 53, 54]. Exercise consistently upregulates nicotinamide phosphoribosyltransferase (NAMPT), the rate‐limiting enzyme for NAD⁺ synthesis, in skeletal muscle. This exercise‐induced NAMPT activation helps maintain intracellular NAD⁺ pools, countering the age‐related decline. Consequently, while supplementation strategies show promise but variability, physical activity remains a proven physiological modulator of NAD⁺ metabolism.

To date, no human study has simultaneously assessed VR or metaverse interventions and blood NAD⁺ levels. This represents a significant gap, as digital experiences strongly modulate the very lifestyle factors—stress, sleep, and physical activity—that govern NAD⁺ flux. Based on the reviewed evidence, we propose three primary theoretical pathways connecting digital experiences to NAD⁺ metabolism:

• 1. Stress Reduction Pathway: VR nature reduces cortisol and inflammation. Since chronic inflammation and DNA damage (via ROS) consume NAD⁺ through PARP and CD38 activation, stress reduction may indirectly “preserve” the NAD⁺ pool [29, 30]. In addition, neuroinflammation represents a key mechanism, as inflammatory processes in the central nervous system are known to increase NAD⁺ consumption via PARP activation, further linking stress responses to metabolic ageing pathways.
• 2. Physical Activity Pathway: Immersive VR exercise (exergaming) elicits MVPA, which activates NAMPT and stimulates NAD⁺ biosynthesis, countering age‐related decline [40, 41, 42, 43, 44, 45, 47].
• 3. Sedentary/Stress Pathway: Conversely, uncontrolled metaverse engagement may accelerate NAD⁺ depletion through chronic stress (cortisol), sleep disruption, and physical inactivity, which are known to impair metabolic homeostasis [16, 17, 18, 19, 49, 50].

To enhance the practical applicability of this conceptual framework, future studies should incorporate standardized measurement protocols. These may include blood‐based NAD⁺ quantification assays, as well as non‐invasive techniques such as 31P‐magnetic resonance spectroscopy (31P‐MRS) to assess cellular energy metabolism. In addition, simultaneous measurement of cortisol levels, inflammatory markers (e.g., IL‐6, CRP), and physical activity metrics (e.g., heart rate, accelerometry) would enable integrated validation of the proposed pathways linking digital experiences to NAD⁺ metabolism.

As shown in Table 2, evidence linking digital experiences with biological ageing markers remains extremely limited, highlighting a critical research gap.

Table 2.

Evidence and research gaps linking digital experiences with biological ageing markers (with references).

Domain	Nature VR/Digital Nature	Metaverse/Urban VR	Immersive VR Exercise (Exergaming)
Key characteristics	Visual and auditory simulation of natural environments.	Immersive, socially interactive digital spaces.	Gamified physical activity using VR headsets.
Impact on stress	Reduction: Lowers cortisol and sympathetic nervous system activity.	Mixed: Enhances social connection but carries risks of sensory overload.	Reduction: Alleviates stress through enjoyment and post‐exercise relaxation.
Impact on physical activity	Low: Typically sedentary or involves light movement.	Low: Primarily sedentary interactions.	High: Elicits moderate‐to‐vigorous physical activity (MVPA).
Proposed NAD⁺ mechanism	NAD⁺ Preservation: Reduced physiological stress may lower NAD⁺ consumption by DNA repair enzymes (PARPs) and immune cells (CD38).	Risk of Depletion: Chronic sedentary behavior may impair NAD⁺ homeostasis; however, social buffering effects remain to be explored.	NAD⁺ Synthesis: Physical activity upregulates NAMPT (rate‐limiting enzyme), directly stimulating NAD⁺ biosynthesis in skeletal muscle.
Implications for healthy ageing	Accessible stress management for individuals with limited mobility or nature access.	Tools for reducing social isolation and providing cognitive stimulation.	Engaging interventions to prevent frailty, sarcopenia, and metabolic decline.

Table 2 summarizes the key mechanisms and research gaps linking digital experiences to biological ageing markers.

4. Conclusion

We propose an integrated conceptual model wherein digital experiences regulate NAD⁺ metabolism via upstream modulation of psychological stress, physical activity, and sleep. While VR nature and exergaming likely support NAD⁺ preservation and synthesis, sedentary digital experiences may pose risks to metabolic health. Validating these pathways with physiological biomarkers represents a crucial next step for research. This framework provides a new foundation for health planning, emphasizing that digital environments are not merely psychological spaces but environmental determinants of biological ageing.

Author Contributions

Tohru Nakajima: conceptualization, investigation, validation, visualization, writing – review and editing, funding acquisition, writing – original draft. Yukio Koibuchi: conceptualization.

Ethics Statement

Ethical approval was not required for this study because it is a narrative review based exclusively on previously published literature.

Conflicts of Interest

The author declares no conflicts of interest.

Transparency Statement

The lead author Tohru Nakajima affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Supporting information

Table S1: List of studies included in the narrative synthesis (n = 50).

Data Availability Statement

No new datasets were generated for this study. All information supporting the findings of this review is contained within the article and its references. Therefore, data sharing is not applicable.