Promoting Healthy Aging: Insights on Brain and Physiological Health - A Special Issue

This special issue aims to provide insights into healthy aging, encompassing various factors influencing it—from molecular and physiological levels to behavioral and lifestyle aspects. Research consistently demonstrates the crucial role of regular physical activity in promoting healthy aging, including brain and physiological health, and preventing age-related disorders like Alzheimer's Disease (AD). The COVID-19 pandemic underscored this, with lockdowns leading to decreased physical activity, increased sedentary lifestyles, and subsequent deterioration of brain and physiological health in the elderly. Maintaining healthy aging necessitates adhering to the World Health Organization's recommendations for weekly physical activity. Studies support resistance training (at least three sessions per week) in middle and late life to mitigate age-related neurological and cognitive consequences, largely through insulin-like growth factor-1 (IGF-1). Furthermore, research using Drosophila melanogaster showed that the probiotic Limosilactobacillus reuteri extends lifespan by reducing IGF-1 signaling. The aging process significantly impacts various physiological systems, including the cardiovascular and respiratory systems. Cardiac aging involves structural and functional modifications, with cellular mechanisms of dysfunction influenced by genetics, epigenetics, and exercise. Long-term physical activity positively regulates the cardiovascular system, reducing basal heart rate and potentially supporting brain and physiological health. Lung function declines with age, primarily due to loss of elasticity, increasing susceptibility to respiratory infections. Improving respiratory health through exercise and smoking cessation helps reduce the risk of lung infections in the elderly. Nutrition is vital, especially for the elderly. Citicoline, a natural metabolite, breaks down into choline and cytidine, with choline being crucial for learning, memory, and neuronal membranes. Citicoline intake improves brain choline uptake, potentially reversing early age-related cognitive decline. Chronic stress is another significant factor accelerating aging and AD. Studies point to chronic stress as a major risk factor for AD, influencing its onset and development. Amyloid beta (Aβ) and tau pathology are involved in AD pathogenesis, although the exact mechanisms remain unclear. Research using Caenorhabditis elegans shows that ATF7 overexpression suppresses aging biomarkers and extends lifespan by reducing cellular senescence and inflammation. The cGAS-STING pathway's role in age-related diseases is also being investigated as a potential therapeutic target. Genetic factors, such as APOE gene mutations, are associated with AD onset, influencing Aβ and tau pathology, inflammation, and vascular integrity. Overlapping molecular pathways exist between AD and age-related retinal diseases. Impaired microglial autophagy contributes to AD pathogenesis by influencing inflammation, Aβ and tau propagation, and synaptic dysfunction. Early intervention is crucial for neurodegenerative diseases like Parkinson's Disease (PD), targeting the prodromal period with lifestyle modifications to reduce risk factors and alter disease progression. Identifying individuals in the prodromal phase allows for early interventions that may alter the disease trajectory. A multimodal approach to risk stratification and combined strategies are proposed for effective interventions.

The special issue draws upon a comprehensive review of existing literature related to healthy aging, focusing on multiple facets including physical activity, nutrition, stress management, and the molecular mechanisms of aging and neurodegenerative diseases. The authors cite numerous studies examining the effects of resistance training, probiotics, citicoline supplementation, and the impact of chronic stress on the aging process and Alzheimer's disease. Moreover, the literature review incorporates research on cardiovascular and respiratory changes during aging, as well as the genetic and molecular underpinnings of neurodegenerative diseases. Specific studies referenced explore the roles of IGF-1 signaling, the cGAS-STING pathway, APOE gene mutations, and microglial autophagy in age-related pathologies. The review also examines the prodromal phase of Parkinson's disease and the potential for early interventions through lifestyle modifications.

This special issue does not present original research findings from a single study but rather synthesizes existing research from various studies to provide a comprehensive overview of healthy aging and neuroprotection. The methodology employed involves a thorough review of the scientific literature related to the topic. The authors have compiled findings from multiple studies across various disciplines, including geriatrics, neuroscience, exercise physiology, nutrition, and molecular biology. The selection criteria for included studies are not explicitly detailed in the provided text; however, it is evident that a wide range of research methodologies were used in the original papers that were reviewed in this special issue (e.g., systematic reviews, meta-analyses, experimental studies using model organisms, human clinical trials). The process of synthesizing this information to create a cohesive narrative is the primary methodological approach of this special issue. There was no original data collection or statistical analysis performed for this special issue; rather, existing published data and conclusions from numerous prior studies were reviewed and integrated.

Key findings presented in this special issue emphasize the importance of lifestyle interventions in promoting healthy aging and preventing age-related neurodegenerative diseases. Regular physical activity, particularly resistance training, plays a vital neuroprotective role by influencing factors such as IGF-1. Probiotics, like Limosilactobacillus reuteri, demonstrate anti-aging effects. Citicoline intake improves choline uptake in the brain and may alleviate age-related cognitive decline. Chronic stress significantly contributes to the development of AD. Molecular mechanisms underlying AD are explored, including the roles of ATF7, the cGAS-STING pathway, APOE gene mutations, and microglial autophagy. Genetic factors associated with AD onset are highlighted. Early identification and intervention in the prodromal phase of neurodegenerative diseases, like PD, are crucial to manage disease progression. The issue also reviews the effects of aging on cardiac and pulmonary systems, highlighting the importance of addressing these factors to maintain overall health. The findings underscore the need for personalized preventative strategies in aging, potentially using biomarkers to identify and address individual risk factors.

The findings presented in this special issue strongly support the notion that a healthy lifestyle significantly impacts aging and the risk of developing neurodegenerative diseases. The integration of various research areas, including molecular mechanisms, genetic predispositions, and lifestyle factors, provides a holistic understanding of the aging process. The emphasis on early intervention, especially for neurodegenerative diseases, highlights the need for proactive healthcare strategies. The interconnectedness of cardiovascular, respiratory, and neurological health is also evident, suggesting a need for integrated approaches to promote healthy aging. Future research should focus on developing personalized interventions based on individual risk profiles, utilizing biomarkers to identify at-risk populations and tailor interventions for optimal outcomes. The importance of addressing modifiable risk factors, such as diet, exercise, and stress management, underscores the potential for preventative medicine to significantly impact healthy aging.

This special issue provides a valuable overview of current knowledge on promoting healthy aging and neuroprotection. It underscores the multifaceted nature of the aging process, emphasizing the interplay between genetic predisposition, lifestyle factors, and molecular mechanisms. The importance of early intervention for neurodegenerative diseases is highlighted, along with the need for future research to develop personalized preventative strategies, ideally leveraging biomarkers to optimize interventions and improve outcomes. The findings support the development of integrated healthcare approaches that address the interconnectedness of various physiological systems in promoting healthy aging.

As a review article synthesizing existing literature, this special issue does not present original research and is limited by the available studies. The methodologies employed in the original studies reviewed are varied, and the heterogeneity of these studies may limit the generalizability of some conclusions. The focus is predominantly on Alzheimer's and Parkinson's diseases, and other age-related conditions may warrant further investigation. Finally, the absence of specific details regarding the selection criteria for the studies included in the review prevents a thorough evaluation of potential biases.