Caroline Barbalho Lamas

Mitochondrial dysfunction is a key contributor to cognitive impairment, directly affecting neuronal viability, synaptic function, and energy metabolism. In the central nervous system, where energy demand is particularly high, disturbances in mitochondrial dynamics, including impaired oxidative phosphorylation (OxPhos), increased reactive oxygen species (ROS) production, and reduced ATP availability, can compromise synaptic transmission and accelerate cognitive decline. These alterations are commonly observed in neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s (PD), in which mitochondrial dysfunction is closely associated with oxidative stress and neuroinflammatory processes. This review aims to investigate the role of mitochondrial dysfunction in cognitive impairment and the effects of physical exercise as a non-pharmacological strategy to mitigate these alterations. Current evidence indicates that exercise promotes mitochondrial biogenesis through activation of the AMPK/PGC-1α pathway, enhances oxidative metabolism, and improves mitochondrial efficiency. Furthermore, exercise reduces oxidative stress and inflammation while stimulating the release of neurotrophic factors, such as brain-derived neurotrophic factor which support neurogenesis, synaptic plasticity, and neuronal survival. Overall, these findings reinforce the importance of mitochondrial integrity in maintaining cognitive function and highlight physical exercise as a promising strategy to counteract mitochondrial dysfunction and delay the progression of neurodegenerative diseases.

In the face of population aging, sarcopenia has emerged as a significant muscle disorder characterized by the progressive loss of muscle mass, strength, and function. Chronic inflammation, oxidative stress, and mitochondrial dysfunction contribute to sarcopenia and help explain its association with comorbidities such as type 2 diabetes, obesity, and neurodegenerative diseases. Despite extensive research, there remains a need to integrate current knowledge on interventions that target these interconnected mechanisms. This review synthesizes recent evidence on the effects of resistance exercise, nutritional supplementation (high-protein intake, leucine, vitamin D, omega-3 fatty acids), and probiotic use on muscle function and inflammatory status in older adults with sarcopenia. Literature was critically analyzed to evaluate the efficacy of multicomponent strategies. The reviewed studies consistently report that combining resistance training with anti-inflammatory nutrition and targeted supplementation improves muscle strength, reduces pro-inflammatory cytokines, and supports mitochondrial function. These findings suggest that an integrated, multicomponent approach represents a promising strategy for attenuating the progression of sarcopenia and reducing its associated comorbidities.

The aging process is closely linked to cognitive decline, and numerous studies have demonstrated a decrease in both the quality and quantity of sleep in the general population. Melissa officinalis (lemon balm) is a plant rich in bioactive compounds, including flavonoids, phenolic acids, and essential oils, which are responsible for its neuroprotective and antidepressant properties. Its positive effects on the sleep quality are probably, at least in part, attributable to the presence of rosmarinic acid, which modulates γ-aminobutyric acid transaminase activity. This review aimed to investigate the effects of M. officinalis on cognition and sleep quality in human clinical trials. For cognition, studies have shown that the plant improved cognitive performance and mood. In elderly individuals with mild cognitive impairment or early Alzheimer’s disease, extracts standardized in rosmarinic acid stabilized cognitive functions and reduced neuropsychiatric symptoms such as agitation. Regarding sleep, a combination of lemon balm and valerian significantly improved sleep quality in postmenopausal women. Isolated lemon balm extracts also reduced sleep disorders in cardiac patients. When compared to citalopram, lemon balm enhanced the quality of life, including sleep quality. It is concluded that lemon balm has the potential to improve cognition and sleep quality; however, robust evidence is needed, as more rigorous trials are required.

Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain’s immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system. Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework. This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical implications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science. The key findings highlight that plants like Cleistocalyx nervosum var. paniala, Curcuma longa, Cannabis sativa, and Dioscorea nipponica reduce pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), inhibit enzymes (COX-2 and iNOS), and activate antioxidant pathways, particularly Nrf2. NF-κB emerged as the primary pro-inflammatory pathway inhibited across studies. While the anti-inflammatory potential of these plants is significant, the variability in dosages and phytochemical compositions limits clinical translation. Here, we highlight that medicinal plants are effective modulators of neuroinflammation, underscoring their therapeutic potential. Future research should focus on animal models, standardized protocols, and safety assessments, integrating advanced methodologies, such as genetic studies and nanotechnology, to enhance their applicability in neurodegenerative disease management.

Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by dysregulation of molecular pathways and activation of the brain's immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacer-bated by peripheral leukocyte infiltration into the central nervous system. Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative condi-tions in a green healthcare framework. This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical im-plications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science. Key findings highlight that plants like Cleistocalyx nervosum var. paniala, Curcuma longa, Cannabis sativa, and Dioscorea nipponica reduce pro-inflammatory cytokines (TNFα, IL-6, IL-1β), inhibit enzymes (COX-2, iNOS), and activate antioxidant pathways, particularly Nrf2. NF-κB emerged as the primary pro-inflammatory pathway inhibited across studies. While the anti-inflammatory potential of these plants is significant, variability in dosages and phytochemical compositions limits clinical translation. Here, we highlight that medicinal plants are effective modulators of neuroinflammation, underscoring their therapeutic potential. Future research should focus on animal models, standardized protocols, and safety assessments, integrating advanced methodologies such as genetic studies and nanotechnology to enhance their applica-bility in neurodegenerative disease management.

Alzheimer’s disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, and neuroinflammation. Despite advancements in early detection, diagnosis, and treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, and the limited efficacy of current therapies. Consequently, there is a pressing need for novel therapeutic agents to target the multifaceted aspects of AD pathology, enhance current treatments, and minimize adverse effects. AdipoRon, an adiponectin receptor agonist, has garnered interest for its potential neuroprotective effects, including reducing neuroinflammation, improving mitochondrial function, and mitigating tau hyperphosphorylation. This review aimed to evaluate the effects of AdipoRon-based adiponectin replacement therapy against AD, using a comprehensive approach grounded in the PICO framework—Population, Intervention, Comparison, and Outcomes. A total of six studies were reviewed, including in vitro and in vivo investigations examining AdipoRon’s impact on various AD models. These studies involved different cell lines and transgenic mouse models, assessing various outcomes such as cognitive function, neuroinflammation, tau phosphorylation, synaptic deficiencies, and relevant molecular pathways. By synthesizing data from these studies, our review thoroughly explains AdipoRon’s neuroprotective effects, mechanisms of action, and potential as a therapeutic agent for AD. This analysis aims to highlight the current state of knowledge, identify gaps in the research, and suggest directions for future studies and clinical applications.

Background/Objectives: Alzheimer’s disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, and neuroinflammation. Despite advancements in early detection, diagnosis, and treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, and the limited ef-ficacy of current therapies. Consequently, there is a pressing need for novel therapeutic agents to target the multifaceted aspects of AD pathology, enhance current treatments, and minimize ad-verse effects. AdipoRon, an adiponectin receptor agonist, has garnered interest for its potential neuroprotective effects, including reducing neuroinflammation, improving mitochondrial func-tion, and mitigating tau hyperphosphorylation. Methods: This review aimed to evaluate the ef-fects of AdipoRon-based adiponectin replacement therapy against AD using a comprehensive approach grounded in the PICO framework—Population, Intervention, Comparison, and Out-comes. Results: A total of six studies were reviewed, including in vitro and in vivo investigations, examining AdipoRon's impact on various AD models. These studies involved different cell lines and transgenic mouse models, assessing various outcomes such as cognitive function, neuroin-flammation, tau phosphorylation, synaptic deficiencies, and relevant molecular pathways. Con-clusions: By synthesizing data from these studies, our review provides a thorough understanding of AdipoRon's neuroprotective effects, its mechanisms of action, and its potential as a therapeutic agent for AD. This analysis aims to highlight the current state of knowledge, identify gaps in the research, and suggest directions for future studies and clinical applications.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating the muscle mass reduction seen in sarcopenia and the decline in neuronal function characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient outcomes. This study emphasizes the complex interplay between vascular dysfunction, muscle degeneration, and cognitive decline, highlighting the necessity for multidisciplinary treatment approaches. Advances in this domain promise improved diagnostic accuracy, more effective therapeutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin’s effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin’s potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2256 documents, leading to the selection of 15 clinical trials for synthesis. Here, we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating muscle mass reduction seen in sarcopenia and the decline of neuronal functions characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review ana-lyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sar-copenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, in-flammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient out-comes. This study emphasizes the complex interplay between vascular dysfunction, muscle de-generation, and cognitive decline, highlighting the necessity for multidisciplinary treatment ap-proaches. Advances in this domain promise improved diagnostic accuracy, more effective thera-peutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.