Abstract: The increasing prevalence of skin-aging and pigmentation disorders, along with inflammation-related pathologies, has driven the search for novel enzyme inhibitors with targeted action against key enzymes such as elastase, collagenase, and tyrosinase. In this context, extracts from Pelargonium graveolens (P. graveolens) flowers were subjected to in vitro and in silico assays to evaluate their inhibitory effects on theses enzymes, as well as the BSA protein denaturation. Additional assessments of emulsification and photoprotective properties were conducted. The hydroethanolic sonication extract demonstrated potent therapeutic potential, with low IC50 values for BSA denaturation (0.31 ± 0.26 mg/mL), tyrosinase (0.06 ± 0.04 mg/mL), elastase (1.29 ± 0.58 mg/mL), and collagenase (0.28 ± 0.14 mg/mL). All extracts effectively reduced surface and interfacial tension, highlighting their potential as natural co-emulsifier. HPLC-PDA-MS/MS analysis identified key bioactive compounds, including shikimic acid, gallic acid diglucoside, and salvianolic acid M. In fact, Binding site prediction revealed that shikimic acid and dihydroxybenzoic acid from P. graveolens extract are likely the key compounds responsible for the inhibitory effects on elastase, collagenase, and tyrosinase. Additionally, trigallic acid appears to play a major role in the inhibition of BSA denaturation. Stability tests of novel formulations-based 2% P. graveolens supporting their potential for commercial applications.

Abstract: While life expectancy has risen, healthspan—the period of life spent in good functional health—has not kept pace. Age-related and chronic diseases are often seen as inevitable decline, but more accurately reflect the cumulative cost of chronic stress adaptation under conditions of bioenergetic and substrate depletion. This review presents a systems-level framework that links aging and chronic disease to prolonged energy and nutrient trade-offs across physiological systems. We introduce the concept of Exposure-Related Malnutrition (ERM)—a subclinical state in which metabolic resources are silently diverted from maintenance and repair toward stress response. Drawing on classical stress models and evidence from immunometabolism, endocrinology, and systems biology, we describe how persistent stress drives resource reallocation across neuroendocrine, immune, muscular, and mitochondrial systems. We outline a shared adaptive trajectory—Respond → Adapt → Resolve—with outcomes shaped by both exposure intensity and metabolic availability. Progressive ERM manifests as anabolic resistance, low-grade inflammation, impaired healing, and lean mass loss—despite adequate intake. Clinical recognition of ERM using tools like pattern-based biomarkers, bioelectrical impedance, and adrenal reserve testing may allow early intervention. By identifying ERM as a reversible precursor to maladaptation, this framework reframes resilience as a metabolically costly process and highlights opportunities to preserve healthspan through upstream strategies.

Abstract: Aging and aging-related neurodegenerative disorders, such as Alzheimer’s disease, are characterized by chronic inflammation that progressively damages nervous tissue within the central nervous system (CNS). In addition to cytokines, lectin-like carbohydrate-recognition molecules play a critical role in modifying cellular communication during inflammation. Among these, galectins-particularly the anti-inflammatory galectin-1 and the pro-inflammatory galectin-3-stand out due to their immunological functions and specificity for N-acetyllactosamine structures. Almost every cell type within the CNS can express and recognize galectins, influencing various essential cellular functions. N-acetyllactosamines, the ligand structures recognized by galectins, are found beneath sialylated termini in protein-linked oligosaccharides. During aging, protein-linked oligosaccharide structures become shorter, exposing N-acetyllactosamines on protein surfaces, which enhances their availability as binding sites for galectins. Genomic studies indicate that the number of galectin-1- and galectin-3-expressing microglial cells increases with age or age related disease (Alzheimer’s disease), reflecting an aging-associated rise in galectin concentrations within the CNS. This increase parallels a rise in free N-acetyllactosamine-like ligands, suggesting that galectin-N-acetyllactosamine interactions gain prominence and play a more significant role in aging-related CNS disorders. Understanding these interactions and their molecular implications offers potential avenues for targeted therapeutic strategies in combating aging-related CNS inflammation and neurodegeneration

Abstract: Hypertension is the leading cause for cardiovascular disease with over 60% prevalence in older adults, its control is complex and requires multidisciplinary approaches. The gut microbiome has shown relevant associations with hypertension development and progression, with some specific bacteria showing potential to explain and improve hypertension. Control of high blood pressure has not been directly associated with the gut microbiome and given its high interindividual variability this relationship is not fully clear. The aim of this study was to characterize the gut microbiome of older adults and to identify bacteria associated with hypertension control. Patients were 60 years and older from Mexico City and the metropolitan area, all were receiving antihypertensive treatment, and donated a feces sample during a routine medical visit. DNA was extracted from 240 samples using a commercial kit, the V3/V4 region of the 16S gene was sequenced and metataxonomic analyses were performed using QIIME and R. Bacterial abundance identified a core microbiome for hypertensive older adults with a decreased diversity with increasing age, but that did not differ for hypertension control. A differential analysis indicated that Escherichia-Shigella increased with age, and that Ruminococcus UCG-002, DTU 089 and several bacteria from the Lachnospiraceae family were distinctively abundant according to hypertension control, with statistical significance for diastolic blood pressure. Our results confirm and expand previous reports on the core gut microbiome of older adults suggesting a abundance changes in fiber fermenting bacteria of the Lachnospiraceae family in uncontrolled hypertension.

Abstract: Background/Objectives: Instrumental Activities of Daily Living (IADL) are key indicators of autonomy and functional ability in older adults with neurocognitive disorders (NCDs). Their performance is influenced by cognitive, motor, and psychosocial factors. However, specific predictors of IADL performance across the NCD spectrum is less well-characterized. This study aimed to identify cognitive, motor, and caregiver-related determinants of IADL in individuals with minor and major NCDs. Methods: A cross-sectional study was conducted in 117 participants referred from a university dementia clinic. Standardized tools for IADL (Lawton IADL Scale), cognition [Addenbrooke’s Cognitive Examination III (ACE-III)], Functional Cognitive Assessment Scale (FUCAS)], motor functions, balance, and mobility [Tinetti Test, Timed Up and Go (TUG)], emotional status [Geriatric Depression Scale (GDS)], neuropsychiatric symptoms [Neuropsychiatric Inventory (NPI)], and caregiver burden [Zarit Burden Interview (ZBI)] were administered. Multiple regression analyses were performed to identify predictors of IADL score. Results: In the total sample (n=117), IADL performance was significantly predicted by ACE-III, FUCAS, and Tinetti-balance, explaining 75.1% of IADL variance. In minor NCD group (n=41), IADL performance was predicted by FUCAS, Tinetti-balance, and ZBI (adjusted R² =0.697). In major NCD group (n=76), ACE-III, FUCAS, Tinetti-balance, and disease duration were significant predictors (adjusted R²=0.673). For all models, worse profile on the previous variables predicted impaired IADL. Conclusions: Global cognitive decline, executive dysfunction in everyday problem-solving situations, balance impairment, and caregivers’ burden are critical determinants of IADL in NCDs. Comprehensive assessments and multidisciplinary interventions, including caregiver support, are essential for health promotion by preserving autonomy and functional independence in older adults.

Abstract: Background: Injectable biostimulators, particularly Poly-L-Lactic Acid (PLLA), have significantly advanced aesthetic medicine by promoting collagen production for skin rejuvenation and volume restoration. This study investigates the efficacy and safety of hyperdiluted PLLA injections in the temples and neck, advocating for customized concentrations to enhance results and minimize risks Objective: To evaluate the clinical efficacy and safety profile of hyperdiluted PLLA injections in the neck and temple region. Materials and methods: All patients were treated with injections of hyperdiluted PLLA (Rennova Elleva®) in the neck and temple region. All patients underwent six-monthly clinical evaluations and kept self-reporting diaries to record any adverse effects during the first 30 days. Patient satisfaction was assessed using the Subject Global Aesthetic Improvement Scale (S-GAIS) on days 90 and 150 post-injection. Results: The study included 16 female patients with a mean age of 50.19 (11.3) years and a mean of BMI: 22.80 (2.2) kg/m². Eight patients (50%) reported mild to moderate injection site reactions, such as redness, pain, hardening, swelling, lumps, bruises, and skin discoloration, with most symptoms resolving within a few days. Clinically, no major adverse events were noted. On post-injection day 90, the average GAIS was 3.1 ± 0.86, indicating an overall “improved” aesthetic appearance, which improved to 2.5 ± 0.97 by day 150 (p=0.12). Conclusion: Hyperdiluted PLLA injections are a safe and effective treatment for facial rejuvenation in the temple and neck areas, offering sustained patient satisfaction and minimal adverse effects. The tailored injection technique, which accounts for unique anatomical characteristics, maximizes results and minimizes complications, highlighting the importance of customized treatment strategies in aesthetic medicine.

Abstract: Background/Objectives: Chronic hyperglycemia, characteristic of type 2 diabetes mellitus (DM2), promotes the development of complications through oxidative stress. Therefore, it is necessary to strengthen the antioxidant defenses of diabetic patients, even more so if they are elderly. Sechium edule contains high amounts of flavonoids, cucurbitacins, and phenolic acids, which is why it is attributed hypoglycemic and antioxidant properties, so our aim was to determine the antioxidant and hypoglycemic effect of Schium edule in older diabetic patients. Methods: A quasi-experimental study was carried out in a convenience sample of 33 older diabetic adults: (i) placebo group (PG; n = 14); (ii) experimental group (EG; n = 19). Glycosylated hemoglobin (HbA1c), lipoperoxides (LPO), protein carbonylation (PC), Total Oxidant Status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), superoxide dismutase, glutathione peroxidase, and catalase enzyme activity were measured at baseline and three months post-intervention. Results: In the EG, a statistically significant decrease in HbA1c was observed (EG baseline 8.9 2.2 post 7.8 2.0), as well as in the oxidative damage markers LPO, PC, TOS and OSI (LPO baseline 0.243 0.067, post 0.222 0.050; PC baseline 29.4 10, post 19.2 6; TOS baseline 6.0 2.6, post 3.1 1.8; OSI baseline 5.7 3.1 post 2.0 1.1); coupled with a significative increase in TAS (baseline 0.94 0.29 post 1.22 0.28), modifications not observed in the PG. Conclusions: Our results suggest that Sechium edule has a hypoglycemic and antioxidant effect in older adults with DM2.

Abstract: Background: Suicidal behavior presents a significant dilemma in the context of Alzheimer's disease. Numerous ethical discussions have emerged regarding euthanasia for patients suffering from neurodegenerative conditions, and research indicates an elevated incidence of suicide in the early stages of dementia. However, there remains a gap in knowledge concerning the historical prevalence of suicidal ideations or attempts among individuals diagnosed with Alzheimer's disease. This study aims to investigate the historical patterns of suicidal behavior and the associated factors across the lifespan in patients with Alzheimer's disease. Methods: This study is an excerpt from case-control research, where the sample was calculated at 150 participants, 75 for the case group and 75 for the control group. Here, the descriptive statistics of the first third of the sample, 50 participants, were made. Results: 12,5% of cases participants had suicidal ideation throughout life and 24% of the control group (OR for suicidal ideation = 0.432 [0.095-1.966]). 4% of cases participants attempted suicide throughout life and 8% of the control group (OR for suicide attempts = 0.479 [0.41-5.652]). Persons with Alzheimer's disease were associated with a worse quality of life and tended to have less suicidality. Conclusions: It appears that suicidal behavior is inversely related to the risk of developing suicide. The odds ratio data demonstrate the need for a larger sample size to determine whether there is a difference in the history of suicide throughout the lives of people with Alzheimer's disease and the general population.

Abstract: In humans, aging is an inevitable consequence of diminished growth processes after being full-grown. The high order of biological material in cells and tissues is continuously disturbed by numerous physical and chemical destructive impacts. Host-derived oxidant-based cytotoxic agents (reactive species, transition free metal ions, free heme) contribute considerably to this damage. These agents are under control by immediately acting antagonizing principles, which are important to ensure cell and tissue homeostasis. During aging, energy metabolism and supply of tissues with dioxygen and nutrients are increasingly disturbed. In addition, a chronic inflammatory state is developing, a condition known as inflammaging. In this review, the interplay between oxidant-based cytotoxic agents and protective mechanisms is analyzed in dependence on age-based physiological alterations in ATP production. Disturbances in this balance are associated with the development of age-related diseases and comorbidities. The enhanced production of reactive species from dysfunctional mitochondria, alterations in cellular redox homeostasis, and adaptations to hypoxia are highlighted. Examples are given how disturbances between oxidant-based cytotoxic agents and antagonizing principles contribute to the pathogenesis of diseases in persons of advanced age.

Abstract: Aging is the result of various compounding stresses that gradually overcome the homeostatic regulation of the cell, resulting in irreversible damage. This manifests as many acute and chronic conditions, the most common of which are neurodegeneration and dementia. Epidemiological studies have shown significant, strong correlations between viral infection and neurodegenerative diseases. This review overlays the characteristics of viral pathogenesis with the hallmarks of aging to discuss how active and latent viruses contribute to aging. Through our contextualization of myriad basic science papers, we offer explanations for premature aging via viral induction of common stress response pathways. Viruses induce many stresses: dysregulated homeostasis by exogenous viral proteins and overwhelmed protein quality control mechanisms, DNA damage through direct integration and epigenetic manipulation, immune-mediated oxidative stress and immune exhaustion, and general energy theft that is amplified in an aging system. Overall, this highlights the long-term importance of vaccines and antivirals in addition to their acute benefits.

Abstract: This study aims to investigate the Vit D status, physical function parameters and analyze their correlation in older nursing home residents with malnutrition risk and malnutrition. Methods: This study was a cross-sectional study and recruited 152 older residents from multiple nursing homes and divided into well-nourished (n=34), malnutrition risk (n=102) and malnutrition (n=16) groups. The nutrition status was evaluated by mini nutritional assessment short form (MNA-SF), then anthropometric data, biochemical blood test and physical function parameters were evaluated and compared among groups. Compared with well-nourished group, BW (body weight), BMI (body mass index), ASMI (appendicular skeletal muscle index) and calf circumference were significantly lower in the malnutrition risk and malnutrition groups. The malnutrition risk and malnutrition groups also represented the significantly higher SOF (study of osteoporotic fractures) score than that of well-nourished group. Three groups showed the Vit D insufficiency that means blood 25(OH)D level is less than 30ng/dL, although there is no difference among three groups. In addition, The MNA-SF was negatively correlated with BMI, ASMI and calf circumference, whereas positively correlated with SOF score. Regarding the odd ratios, when the score of MNA-SF was low, the odds ratios of low ASMI, low calf circumference, and high SOF score were significantly increased. The institutionalized older adults with malnutrition risk or malnutrition had lower ASMI and calf circumference. However, regardless of nutritional status, occurrence of Vit D insufficiency was observed, and Vit D showed no significant correlation with physical function parameters among the older adults in the nursing home.

Abstract: Hyaluronic acid (HA) content in the skin progressively decreases with age, thus its supplementation - either topical, oral and by subcutaneous injection - represents a first line intervention to ameliorate skin aging signs. The present multicenter randomized placebo-controlled trial (RCT) evaluated the skin antiaging efficacy of an In&Out treatment, i.e. a concomitant topical, through a cosmetic cream, and oral administration of a specifically designed HAs, the Full Spectrum HAs (FS-HA), in a multiethnic population by instrumental measurements and clinical assessments. Efficacy of FS-HAs was evaluated also in groups receiving FS-HA in a single administration route and in presence of the placebo in the counterpart route. The above treatment scheme was applied for fifty-six days to eighty-eight adult subjects, equally divided in four groups. Treatments containing at least one FS-HA molecule showed progressive and significant intragroup ameliorations of all instrumental skin parameters evaluated. The In&Out treatment resulted in a higher improvement with respect to the two other active groups and in significant intergroup differences with respect to its placebo counterpart. FS-HA treatments resulted, as well, in significant improvements of clinical parameters that correlated with the subjects’ appreciation recorded by a Self-Assessment, hence confirming that the In&Out administration of FS-HA represents an interesting approach to counteract skin aging signs.

Abstract: Aging is an extensive biological process characterized by morphological and functional alterations in cellular and extracellular components, resulting in a systematic decline in biological functions ultimately leading to death. Although substantial advancements have been made in manipulating lifespan in model organisms like C. elegans and mice through genetic, dietary, and pharmacological means, the fundamental mechanisms driving aging in humans remain elusive and widely debated. In addition, there is no comprehensive computational platform capable of making predictions on aging in multicellular systems and integrating the multiscale competency of lifeforms. We focus on the processes that build and maintain a complex anatomy toward a specific target morphology, and propose the hypothesis that aging arises even in the absence of accumulated cellular or genetic damage, because a homeodynamic system left without any goal in anatomical morphospace will start degrading. This can occur in biological systems because evolution typically prioritizes development over morphostasis, leaving organisms with limited reinforcement of anatomical goals after development. Using an in silico model of homeostatic morphogenesis with a multiscale competency architecture and information dynamics analysis, we find: (1) Absence of Long-Term Morphostasis: Aging emerges naturally after development due to the lack of an evolved regenerative goal, rather than just specific detrimental properties of developmental programs (e.g., antagonistic pleiotropy or hyperfunction); (2) Acceleration Factors vs. Root Cause: Cellular misdifferentiation, reduced competency, communication failures, and genetic damage all accelerate aging but are not its primary cause; (3) Information Dynamics in Aging: Aging correlates with increased active information storage and transfer entropy, while spatial entropy measures distinguish two dynamics—loss of structure and morphological noise accumulation; (4) Dormant Regenerative Potential: Despite organ loss, spatial information persists in the cybernetic tissue, indicating a memory of lost structures, which can be reactivated for organ restoration through targeted regenerative information; and (5) Optimized Regeneration Strategies: Restoration is most efficient when regenerative information includes differential patterns of affected cells and their neighboring tissue, highlighting strategies for rejuvenation. These findings provide a novel perspective on aging dynamics with significant implications for longevity research and regenerative medicine.

Abstract: Aging increases oxidative stress (OS) in the ovaries, leading to infertility-related dis-orders. Granulosa cells (GCs), which support folliculogenesis in the ovaries, are chron-ically exposed to excessive OS under pathological conditions. Here, we demonstrate the significant role of Rubicon, an autophagy suppressor, as a DNA damage mediator in GCs under OS. Hydrogen peroxide (H2O2) decreased cell viability in the human GC cell line, HGrC1, due to DNA damage, without affecting autophagic activity. However, activation of autophagy increased OS resistance in HGrC1 cells, and vice versa. Among several materials that are considered safer for clinical use, trehalose, a disaccharide, exerted a protective effect as an autophagy activator against H2O2-induced cytotoxici-ty. Trehalose significantly increased autophagic activity, accompanied by a reduction in Rubicon, compared to other carbohydrates. It also reduced the expression of DNA damage-responsive proteins and the production of reactive oxygen species. The reduc-tion in Rubicon expression by siRNA mitigated DNA damage caused by OS, while overexpression of Rubicon enhanced DNA damage and decreased HGrC1 cell viability. Trehalose enhanced OS resistance by activating autophagy and suppressing Rubicon in a bidirectional manner. As Rubicon expression increases in aged human ovaries, tre-halose may improve ovarian function in patients with infertility and other OS-related diseases.

Abstract: Over 400 articles on the pathophysiology of brain aging, neuroaging and neurodegeneration were reviewed, with a particular focus on epigenetic mechanisms and numerous non-coding RNAs, in particular microRNAs, the discovery of whose pivotal role in gene regulation was recognized by the 2024 Nobel Prize in Physiology or Medicine. Aging is not a gradual process that can be easily modeled and described. Instead, multiple temporal processes occur during aging, and they can lead to mosaic changes that are not uniform in pace. The rate of change depends on a combination of external and internal factors and can be boosted in accelerated aging. The rate can decrease in decelerated aging due to individual structural and functional reserves created by cognitive, physical training or pharmacological interventions. Neuroaging can be caused by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle, and environmental factors, which is especially noticeable in space environments where adaptive changes can trigger aging-like processes. Numerous candidate molecular biomarkers specific for neuroaging need to be validated to develop diagnostics and countermeasures.

Abstract: Mitochondria, often referred to as the powerhouses of the cell, are essential for cellular metabolism and energy production. While their function is primarily regulated by both nuclear and mitochondrial DNA, recent research suggests that modifications to mitochondrial RNA (mtRNA) play a crucial role in shaping mitochondrial activity, maintaining cellular energy balance, and influencing the aging process. This review delves into the emerging field of mitochondrial epitranscriptomics, focusing on key RNA modifications such as N6-methyladenosine (m6A), pseudouridylation, and 5-methylcytosine (m5C), and their role in regulating mitochondrial gene expression and function. We explore how these modifications affect oxidative phosphorylation (OXPHOS), the balance of reactive oxygen species (ROS), and cellular senescence. Additionally, we highlight advanced techniques used to study mitochondrial RNA modifications and examine how their dysregulation is linked to aging and age-related diseases. Finally, we discuss the potential of targeting these modifications for therapeutic interventions. A deeper understanding of mitochondrial epitranscriptomic changes could pave the way for novel approaches to treating neurodegenerative diseases, metabolic disorders, and promoting healthy aging.

Abstract: Alzheimer’s disease (AD) is a complex, genetically heterogeneous disorder. The diverse phenotypes associated with AD result from intricate interactions between genetic and environmental factors, influencing multiple biological pathways throughout disease progression. Network-based approaches offer a comprehensive way to assess phenotype-specific states. In this study, we calculated key network metrics to characterize the network transcriptional structure and organization in LOAD, focusing on genes and pathways implicated in AD pathology within the dorsolateral prefrontal cortex (DLPFC). Our findings revealed disease-specific coexpression markers associated with diverse metabolic functions. Additionally, significant differences were observed at both the mesoscopic and local levels between AD and control networks, along with a restructuring of gene coexpression and biological functions into distinct transcriptional modules. These results show the molecular reorganization of the transcriptional program occurring in LOAD, highlighting specific adaptations that may contribute to or result from cellular responses to pathological stressors. Our findings may support the development of a unified model for the causal mechanisms of AD, suggesting that its diverse manifestations arise from multiple pathways working together to produce the disease’s complex clinical patho-phenotype.

Abstract: Physiologic aging and insults from the environment lead to DNA damage. In response, cells in any organ will undergo senescence-induced growth arrest to prevent damaged cells from further propagation. This review focuses on senescence pharmacology. First, we describe senescence induction mechanisms and a unique feature of senescent cells, the SASP (senescence-associated secretory phenotype). Signaling pathways that control and respond to the SASP provide the framework for a better understanding of senescence pharmacology. We describe how several commonly used drugs can induce cellular senescence and how that impacts their efficacy and produces unexpected effects. Thereafter, we discuss the potential and challenges of senolytic drugs that eliminate senescent cells, and we describe targeting of components of the SASP as well as pathways that control expression of genes contributing to the SASP. Lastly, we discuss studies that have exemplified the significant impact of senescence-targeted therapy in various disease states.

Abstract:

A major challenge in aging research is identifying interventions that can improve lifespan and health and minimize toxicity. Clinical studies cannot consider decades-long follow-up periods, and therefore, in-silico evaluations using omics-based surrogate biomarkers are emerging as key tools. However, many current approaches train predictive models on observational data, rather than on intervention data, which can lead to biased conclusions. Yet, the first classifiers for lifespan extension by compounds are now available, learned on intervention data. Here, we review evaluation methodologies and we prioritize training on intervention data whenever available, highlight the importance of safety and toxicity assessments, discuss the role of standardized benchmarks, and present a range of feature processing and predictive modeling approaches. We consider linear and non-linear methods, and automated machine learning workflows. We conclude by emphasizing the need for explainable and reproducible strategies, the integration of safety metrics, and the careful validation of predictors based on interventional benchmarks.

Abstract:

Introduction: Alzheimer's is a neurodegenerative disease characterized by a progressive decline in cognitive and motor functions. This research proposes an innovative multimodal hypothesis. According to the hypothesis, the loss of emotionally engaging interests and goals in at-risk individuals leads to a reduction in conscious goal-oriented activities. Not only are enacted movements affected, but also those imagined during mental travels. Investigating these mechanisms can significantly accelerate research on apraxias and Alzheimer's. Method: A review of multidisciplinary literature on hemispheric connection and disconnection, proprioception, embodied cognition, motor language, and the syntax and semantics of gestural actions, among other topics, is employed to support the proposed hypothesis. From theoretical speculation, entirely new interpretations of motor-cognitive degenerations emerge. Discussion: Healthy connectivity between the dominant and contralateral hemispheres consists of a functional tension where data integration is complementary. The left hemisphere articulates already learned gestures into chains experienced as advantageous for achieving a goal, working towards maximum efficiency in goal-oriented action. In contrast, the right hemisphere provides a repertoire of gestural units with intrinsic meaning, independent of chains, to be used when execution on the left is interrupted or when more creative solutions are required. Conclusion: The lack of interhemispheric dialogue results in the atrophy of neural contacts capturing contralateral inputs, with progressive necrosis leading to the formation of amyloid plaques and advanced cerebral atrophy. The root cause of this lack of dialogue lies in the loss of value-driven motivations, particularly existential ones.