Fuellen et al. (2025) highlighted the essential role of explainable AI methods, particularly principal component analysis (PCA), in evaluating interventions for aging and longevity. However, this paper raises significant concerns regarding PCA's linear and parametric nature, which can misrepresent complex, nonlinear data common in geroscience research. As biological relationships often defy simplistic interpretations, reliance on PCA may obscure vital insights, leading to potential misinterpretations of intervention effects. To enhance accuracy in analyses, this study advocates for the adoption of nonlinear and nonparametric methods, such as Spearman's rank correlation and Kendall's tau. By reconsidering their methodological approaches, researchers can foster more accurate and informed evaluations of aging-related interventions.

This review explores the anti-ageing potential of nine repurposed drugs: aspirin, atorvastatin, enalapril, metformin, canagliflozin, liraglutide, acarbose, N-acetylcysteine and dasatinib (commonly combined with quercetin). Specifically, it focuses on their mechanisms through the mechanistic target of rapamycin, adenosine monophosphate-activated protein kinase, nuclear factor kappa B and senescence-associated secretory phenotype pathways. The repurposed drugs show promise in extending healthspan and lifespan in model organisms by modulating ageing-related processes, e.g. reducing chronic inflammation, enhancing metabolic efficiency and improving cellular stress resistance. However, translating preclinical findings into clinical practice still faces major challenges, including species specificity and sex differences, the lack of reliable ageing biomarkers and the issue of dosage selection. This review synthesises progress and obstacles in transitioning drug development from targeting individual age-related diseases to addressing ageing as a unified biological process. Ultimately, the goal is to support a paradigm shift where ageing is recognised as a modifiable condition, enabling longer healthy human lifespans.

Sepsis is a common and highly fatal condition in intensive care units and is one of the leading causes of death worldwide. As a clinically complex syndrome with intricate pathophysiology, early identification and assessment of sepsis remain challenging. Deeper insights at the molecular level are crucial for understanding the complex pathophysiological mechanisms, discovering new biomarkers, and improving prognosis. Post-translational modifications (PTMs) refer to the attachment of specific chemical groups to amino acid side chains through covalent, enzymatic, or non-enzymatic means, greatly expanding protein diversity and playing critical roles in many cellular signaling pathways. Here, we elucidate the regulatory roles of PTMs in sepsis pathways and key proteins, including immune response, late-stage inflammatory mediators, cellular metabolic reprogramming, and endothelial injury. We also summarize the progress in research on PTM-related sepsis biomarkers, covering diagnosis, prognosis, and organ dysfunction assessment, with a particular focus on the potential of glycosylation as a biomarker. Furthermore, we review current methodologies for studying PTMs. Continued focus on PTMs will pave the way for new possibilities in sepsis research and treatment.

Alzheimer's disease (AD) is the most common neurodegenerative disorder associated with dementia. Cellular senescence, widely acknowledged as a key hallmark of aging, has increasingly been recognized as a significant factor in the pathogenesis of AD, although the precise mechanisms underlying this relationship have yet to be fully understood. In the brains of individuals with AD, neurons, glial cells, and cerebrovascular endothelial cells exhibit premature senescence, characterized by irreversible cell cycle arrest, resistance to apoptosis, and the secretion of a diverse range of bioactive molecules collectively referred to as the senescence-associated secretory phenotype (SASP). These senescent cells profoundly influence the neural microenvironment through the release of SASP factors, thus exacerbating Aβ- and tau-induced neurotoxicity, promoting neuroinflammatory responses, and impairing the integrity of the blood-brain barrier (BBB), ultimately giving rise to a self-sustaining "senescence-neurodegeneration" cycle. Despite progress in therapies targeting Aβ and tau pathology, their clinical effectiveness remains limited, highlighting the urgent need for alternative therapeutic strategies. This review presents a comprehensive analysis of the molecular mechanisms connecting AD with cellular senescence, examines how the senescent microenvironment contributes to neurodegeneration, and evaluates the therapeutic potential of senotherapeutic interventions-including senolytics and senomorphics-as novel approaches for the clinical management of AD.

The global population is aging rapidly, extending into the oldest old. However, increased longevity does not always translate into enhanced health. While genetic and environmental factors influence lifespan, evidence indicates that targeted interventions can substantially enhance the likelihood of reaching 100 years. This study aimed to characterize disease and risk factor patterns among the oldest-old to identify actionable targets for promoting health and functional capacity in this rapidly growing population.

Aging-related retinal diseases lead to irreversible structural damages and vision loss. These conditions are characterized by cellular senescence, oxidative stress, neural degeneration, and neovascularization. Among these, chronic inflammation is a hallmark of aging, establishing a self-perpetuating vicious cycle that accelerates pathological process and physiological decline. cGAS-STING signaling pathway has been identified as a critical mediator of inflammation across multiple retinal disease contexts, functioning to regulate immune response by detecting the dsDNA resulted from tissue injury. Under pathological circumstances, it exhibits a state of persistent activation, which results in chronic inflammatory reactions in the microenvironment. The disrupted homeostasis is closely linked with the onset and progression of numerous aging-related retinal diseases. Given the strong association between cGAS-STING signaling and these conditions, this pathway may represent a promising therapeutic target for refractory retinopathies. Encouragingly, several inhibitors targeting this pathway have already been developed and yielded remarkable therapeutic outcomes. This review delineates the primary functioning factors and modulatory mechanisms of the cGAS-STING cascade. Furthermore, it discusses the specific role of cGAS-STING pathway in pathological process of age-related retinopathy and summarize the key inhibitors of the cGAS-STING pathway, highlighting their therapeutic potentials for age-related retinopathy. These findings will deepen the understanding of the crosstalk between cGAS-STING signaling and retinal aging, thus offering valuable insights for the future translation of laboratory findings into clinical interventions.

The relationship between metabolic and inflammatory adaptations with exercise training is poorly quantified. We employed a novel meta-analytical approach to provide an evidence-based framework to guide exercise prescription for health in older adults.

Alzheimer's disease (AD) is the predominant cause of cognitive dysfunction, with global prevalence increasing annually. AD progression is principally driven by the accumulation of amyloid-β (Aβ) and hyperphosphorylated microtubule-associated protein tau (p-Tau), which trigger a subsequent cascade of neuroinflammatory responses within the central nervous system (CNS). This pathological cascade is regulated by reciprocal CNS-peripheral immune crosstalk. The brain-spleen axis has emerged as a critical conduit that orchestrates splenic immune activity and CNS-peripheral immune crosstalk during AD progression. Notably, through the brain-spleen axis, early-life and preclinical exercise may restore splenic vagal-sympathetic homeostasis, re-establish immune equilibrium, and then mitigate neuroinflammation. This review advances a testable hypothesis that early exercise prevents or attenuates AD pathology through the brain-spleen axis, potentially accelerating the development of innovative therapeutic targets such as non-invasive brain stimulation.

Lecanemab and donanemab are the first anti-amyloid monoclonal antibodies (mAbs) clinically available as disease-modifying therapies for Alzheimer's disease (AD). However, it remains unclear whether their treatment effects differ across demographic, clinical, or genetic subgroups.

Huntington's Disease (HD) is a neurodegenerative, genetic disorder that affects the brain and is caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide in the huntingtin (HTT) gene exceeding 35 units. Further, the mutation occurs, which leads to the generation of mutant huntingtin (mHTT) protein, which is a toxic protein that damages the neurons and their functions, leading to disease progression. Phosphorylation, SUMOylation, O-GlcNAcylation, and ubiquitination are some of the post-translational modifications (PTMs) that affect the toxicity, location, and aggregation of this altered protein. The survival of neurons depends on autophagy, vesicle trafficking, transcriptional control, and mitochondrial function, all of which are disrupted by HTT. This protein tends to form aggregates, which disrupt vital neuronal functions and ultimately result in neuronal death, especially in the cortex and striatum. The three clinical manifestations of HD include mental health problems, cognitive impairment, and motor symptoms (bradykinesia, chorea). In this review, the HTT protein is examined, along with its normal functions, post-translational modifications, and role in HD pathogenesis. The therapeutic intervention under investigation includes PTM-targeted medications, which are those drugs that enhance neuroprotection and proteostasis, and gene silencing strategies such as antisense oligonucleotides and RNA interference. Disease models are being improved with several novel approaches, which include induced pluripotent stem cells (iPSCs) and CRISPR-based editing and preclinical models. By integrating these technologies, the mechanisms of the underlying disease have also been enhanced. The recent treatment approaches have also been explored by using molecular targets and diagnostic tools, including FANCD2 and FANCI-associated nuclease 1 (FAN1), which are genetic regulators of somatic CAG expansion; EPS8 dysregulation, which causes protein aggregation; and mismatch negativity (MMN), which is a brain response detected by EEG, a non-invasive biomarker for early cognitive impairment. These measures aim to slow down disease progression and improve the health and outcomes of patients.

Multivitamin and mineral (MVM) supplements are among the most widely used dietary supplements globally, however, their role in promoting healthspan and longevity remains unclear. This review evaluated comprehensive findings from meta-analyses to clarify their health effects. A rapid review of MEDLINE and EMBASE identified 19 eligible meta-analyses published from 2000 to 2025, encompassing 5535,426 participants, including over 333,943 pregnancies and 904,947 children exposed to maternal MVM supplementation. Randomized controlled trials indicated that MVM use improved global cognition, episodic memory, and immediate recall in older or cognitively intact adults, reduced psychological symptoms in healthy individuals, and lowered systolic blood pressure in at-risk populations. However, no benefits were found for all-cause mortality, COVID-19 outcomes, visual acuity, or multiple cognitive domains, and a higher risk of age-related macular degeneration progression was reported. Observational studies found associations between MVM use and a reduced risk of colorectal cancer, coronary heart disease, cataracts, and fragility hip fractures, but not breast or prostate cancer, stroke, or overall mortality. During pregnancy, MVM supplementation was linked to reduced risks of small-for-gestational-age births and pediatric cancers, but not to preterm birth, stillbirth, or low birth weight. Overall, the findings revealed a lack of consistency in the definition of MVM supplementation, and substantial variability in MVM effectiveness depending on population, age, and health status. These results highlighted the importance of shifting from generalized supplementation approaches to more targeted, personalized nutritional strategies to support healthspan and longevity.

Multiple sclerosis has been closely related to the dysfunction of Glial cells, focusing on astrocytes, oligodendrocytes, and microglia. The prevalence of Multiple sclerosis has increased in India but diagnosis and treatment also remain a factor that severely impacts a patient's social duties and family's well-being. Severe disability and cognitive impairment predict job loss, declining standards of living. These cells serve an essential role in maintaining normal homeostasis and facilitating neuronal activity, while also contributing significantly to neuroinflammation. The glial cell dysfunction occurs via multiple pathways, such as demyelination, reactive astrocytosis, and microglial activation, all of which have a role in the pathogenesis and progression of multiple sclerosis. The existing therapeutic methods, including disease-modifying therapies and symptomatic management, address novel tactics aimed at glial cells, namely in the areas of remyelination and immunomodulation. A robust literature survey underlines the significance of comprehending the complex interplay between glial cells and the immune system in multiple sclerosis, indicating that this insight may facilitate more targeted and individualized therapeutic strategies. The current review is focused on understanding the role of glial cells in multiple sclerosis pathology, the current treatments available, and possible potential therapeutics for Multiple sclerosis management.

Alzheimer's disease (AD), the most common cause of dementia, is characterized by amyloid-β deposition, tau hyperphosphorylation, neuroinflammation, and progressive neuronal loss, with no curative therapy currently available. Dental pulp stem cells (DPSCs) derived from third molars represent an ethically accessible, minimally invasive, neural crest-derived mesenchymal stem cell source with self-renewal and multi-lineage differentiation potential. Preclinical evidence suggests that DPSCs exert neuroprotective effects by reducing oxidative stress and apoptosis, enhancing neurogenesis through synaptic repair and neuronal differentiation, and modulating neuroinflammation via microglial regulation. Their secretion of neurotrophic factors, including BDNF, GDNF, NGF, NT-3, CNTF, and HGF, further supports neuronal survival and functional recovery in Alzheimer's disease models. Advances in 3D neurosphere and brain organoid models demonstrate the integration of DPSCs into neural circuitry, highlighting their translational potential. Nevertheless, challenges such as cell survival, migration, and functional integration within the diseased brain remain. Importantly, the use of extracted third molars avoids major ethical concerns associated with embryonic stem cells, making DPSCs a clinically relevant candidate for regenerative approaches. Future directions emphasize the development of exosome-based therapies, bioengineered scaffolds, gene-modified DPSC strategies, and personalized autologous interventions. Collectively, current evidence positions third molar-derived DPSCs as a promising avenue for disease-modifying and regenerative therapies in Alzheimer's disease.

Photoaging is a process of accelerated skin aging induced by ultraviolet radiation (UVR) and other exogenous factors, characterized by deepened wrinkles, collagen degradation, and inflammatory responses. With increasing public interest in maintaining healthy skin and delaying aging, natural proteins and their bioactive peptides have emerged as promising candidates in anti-photoaging research due to their potent antioxidant, anti-inflammatory, and extracellular matrix (ECM) metabolism-regulating activities. Therefore, this review focuses on natural anti-photoaging peptides (APPs) and summarizes the latest research advances in their application in skin photoaging, covering their sources, preparation methods, clinical studies, and anti-photoaging mechanisms. It places particular emphasis on the roles of different types of bioactive peptides in skin protection, functional regulation, and aging intervention, while also conducting an in-depth discussion on the current challenges faced in their practical applications and their prospects. The results showed that APPs can significantly alleviate skin damage caused by ultraviolet radiation through multi-target mechanisms of action, and some peptides have completed clinical validation. In the future, APPs are expected to demonstrate broad application potential in dietary nutritional interventions and anti-aging strategies.

Aging is the primary risk factor for cardiovascular disease, cancer, neurodegeneration, and other chronic disorders. Therefore, targeting the hallmarks of aging has emerged as a promising strategy to extend healthspan. Liver X receptors (LXRs) are ligand-dependent nuclear receptors that are activated by specific oxysterols and cholesterol derivatives. They are traditionally known as key regulators of cholesterol homeostasis. However, recent evidence reveals that LXRs also influence autophagy, mitochondrial function, epigenetics, senescence, stem cell dynamics, and intercellular communication. This positions LXRs at the crossroads of multiple hallmarks of aging. This review synthesizes current knowledge on endogenous and synthetic LXR ligands, their transcriptional mechanisms, and their effects on the aforementioned hallmarks and age-related pathophysiology. The clinical development of pan-LXR agonists for atherosclerosis has been hindered by side effects, notably hepatic steatosis. Emerging strategies, including LXRβ-selective ligands, selective LXR modulators (SLiMs), and biased agonists such as dendrogenin A, offer ways to separate the protective vascular, metabolic, and neuroprotective effects from adverse outcomes. Additionally, we explore how LXR signaling intersects with the hallmarks of aging and how it can be leveraged to intervene in atherosclerosis, diabetes, cancer, osteoporosis, age-related macular degeneration, and neurodegenerative diseases. Positioning LXRs within the geroscience framework suggests that LXRs may serve as pharmacological hubs to delay aging and its comorbidities. Future work should prioritize isoform- and tissue-selective approaches, metabolite-inspired ligand design, and integration with the hallmarks of aging to unlock the full therapeutic potential of LXRs.

Emotion assessment in dementia care is vital for patient well-being and effective care planning. Traditional methods are often subjective and time-consuming. This study examines the use of AI-based facial expression analysis for emotion recognition in dementia patients. A scoping review was conducted using the SPIDER strategy. Five databases-PubMed, Scopus, PsycInfo, ProQuest, and IEEE Xplore -were consulted, with additional records identified through snowballing. Data on participant characteristics, intervention details, non-AI comparisons, and clinical outcomes were categorized. Two authors independently screened records and extracted data on AI driven tools. The review analyzed 11 studies, primarily using deep neural networks. While most studies relied on pre-existing datasets, some collected original data. The studies focused on assessing a variety of emotions, with an emphasis on detecting basic emotions and, in some cases, more complex emotional states. AI applications included early detection, diagnosis, intervention impact assessment, and reliability testing. Comparisons were made with traditional assessment tools. This scoping review highlights the potential of AI tools to improve dementia care. However, standardized data collection and processing protocols are needed to advance AI in emotion recognition for dementia patients. Integrating multiple data sources and addressing dataset limitations are crucial for improving model accuracy and representativeness. Ethical considerations, including privacy and data security, must be prioritized when developing and implementing AI tools in this population. Interdisciplinary collaboration is essential to fully harness their potential.

This review delves into the intricate relationship between serotonin signaling, mitophagy and mitochondrial dysfunction in Alzheimer's disease (AD), with a focus on the mechanistic pathways that link these processes and their potential therapeutic implications. A neurodegenerative condition called Alzheimer's disease is marked by cognitive deterioration. It is increasingly recognized as being influenced by impaired mitochondrial function and mitophagy, the selective degradation of damaged mitochondria. Serotonin, a neurotransmitter traditionally known for its role in mood regulation, has emerged as a critical modulator of mitochondrial dynamics and quality control through its interaction with key pathways such as the PINK1-Parkin and cAMP/PKA signaling pathways. In AD, alterations in serotonin levels and receptor function are associated with disruptions in mitophagy, leading to the accumulation of dysfunctional mitochondria, increased oxidative stress, and subsequent neuronal damage. This review synthesizes current evidence that links serotonin dysregulation to mitochondrial pathology in AD, exploring how impaired serotonin signaling exacerbates mitochondrial dysfunction and contributes to amyloid-beta (Aβ), phosphorylation of Tau (p-Tau) accumulations, and increased neuroinflammation. Additionally, we assessed the therapeutic potential of serotonin-targeting agents, particularly selective serotonin reuptake inhibitors (SSRIs), in restoring mitophagy, enhancing mitochondrial integrity, and attenuating neurodegeneration. By highlighting existing knowledge gaps and key controversies, this review underscores the promise of serotonin-mitochondria pathways as novel therapeutic targets and advocates for focused investigation into receptor-specific, mitophagy-centered interventions for AD.

The prevalence of diabetes among the elderly population has been rising rapidly. Elderly individuals with diabetes frequently exhibit atypical symptoms, and face an increased risk of severe complications, comorbidities and geriatric syndromes, including hypoglycemia, sarcopenia, cognitive impairment, depression, and falls. These issues not only diminish quality of life, but also contribute to elevated disease burden. Conventional diabetes management strategies for this population often fall short due to their invasive nature, limited capacity for real-time monitoring, and poor patient adherence. The emergence of artificial intelligence (AI) in medicine offers a transformative solution to these challenges. Fueled by large-scale datasets, advanced machine learning algorithms, and state-of-the-art computational techniques, AI enables non-invasive, real-time monitoring systems and delivers personalized diagnostic and treatment solutions for this population. This review comprehensively explores the role of AI in managing diabetes and its comorbid conditions among older adults, highlighting its applications in screening, diagnostic, monitoring, and therapeutic strategies. It also addresses the practical challenges and ethical considerations of integrating AI into clinical practice.

Among the marine bioresources, sea urchins are emerging as a promising provider of bioactive compounds with broad therapeutic potentials, including for ageing and age-related diseases. This review highlights the therapeutic promise of sea urchin bioactive compounds, covering evidence from both laboratory and clinical studies. Compounds found in sea urchin such as carotenoids, polyhydroxynaphthoquinones (PHNQs), and flavonoids demonstrate antioxidant and anti-inflammatory properties with notable cell viability improvements, targeting conditions like metabolic syndrome, cardiovascular disease, neurodegenerative disorders, as well as ophthalmic, dermatological, and post-menopausal conditions. Sea urchins hold great nutritional value, rich in proteins, minerals, and trace elements, which further supports their potential health benefits in humans. However, challenges remain, including the risk of adverse effects at high doses, limited bioavailability, species-specific bioactivities, and the limited understanding of their molecular mechanisms of action. Future research should focus on elucidating these mechanisms, as well as conducting rigorous preclinical and clinical investigations to validate their therapeutic efficacy. With continued research, we shall develop strategies for the best use of sea urchins including for health benefits.

Type 2 diabetes is associated with increased Alzheimer's disease risk and brain beta amyloid (Aβ) burden, suggesting an underlying mechanistic relationship between Alzheimer's disease and type 2 diabetes. Animal studies show exercise reduces levels of brain Aβ and tau, and while human studies are somewhat limited, some studies have reported physical activity is associated with lower brain Aβ and tau levels. Exercise has well established links to reductions in insulin resistance; thus, as physical activity can impact both insulin resistance and Alzheimer's disease pathology and/or biomarkers, it is reasonable to hypothesise that a mediating relationship may exist. The objective of this review was to identify what evidence exists that examines the association between insulin, physical activity, Aβ and tau in research conducted on animal models and in human cohorts. We specifically aimed to identify whether insulin resistance has a mediating role in the relationship between physical activity and Aβ and tau.

The adoption of digital therapeutics among older adults presents both opportunities and challenges in modern healthcare. While these technologies enhance disease management, autonomy, and quality of life, engagement remains hindered by cognitive, emotional, systemic, and sociocultural barriers. This narrative review synthesizes findings from 76 peer-reviewed studies identified through Scopus and Web of Science (2010-2024) to examine key factors influencing geriatric engagement with digital therapeutics. FINDINGS: indicate that technological illiteracy, privacy concerns, usability challenges, and mistrust in digital platforms significantly limit adoption. Additionally, cultural attitudes, generational skepticism, and infrastructural limitations exacerbate digital disparities. Conversely, personalized health benefits, caregiver and peer support, and intuitive design features serve as key motivators for adoption and sustained engagement. To enhance digital inclusion, this review highlights the need for user-centered design principles, tailored digital literacy programs, and systemic policy interventions, such as broadband expansion and privacy safeguards. Future research should explore longitudinal engagement patterns, culturally adaptive digital interventions, and the integration of behavioral and technological frameworks to optimize geriatric digital health solutions. Addressing these factors will be essential to ensuring equitable, inclusive, and effective digital therapeutics for aging populations worldwide.