Search Results (619)

Engineered mesenchymal stem cells (MSCs) have emerged as promising therapeutic platforms for healthspan-relevant applications. As agents of tissue repair and modulators of biological aging, MSCs have been widely studied for their capacity to enhance regeneration, restore immune homeostasis, and reduce chronic inflammation associated with age-related decline. This review examines emerging bioengineering strategies designed to overcome key age-related limitations in MSC homing, survival, and paracrine signaling, which have historically constrained their in vivo efficacy. We discuss major engineering approaches, including genetic modification, surface engineering, metabolic reprogramming, and preconditioning, with particular attention to their contributions to longevity-focused applications. Preclinical studies have demonstrated that engineered MSCs and their extracellular vesicles (EVs) yield measurable improvements in therapeutic performance. Reported benefits include prolonged persistence in inflamed tissues, partial reversal of senescence-associated phenotypes, and modulation of pro-aging inflammatory pathways. While MSC-derived EVs may offer potential safety advantages and could reduce certain risks associated with live-cell administration, this remains to be confirmed in well-controlled clinical studies, and significant challenges persist in terms of manufacturing scalability, cargo consistency, and process standardization. The current literature, which is predominantly preclinical, supports the potential of engineered MSC platforms to improve healthspan-relevant outcomes; direct evidence of healthspan extension in humans is not yet available. However, successful clinical translation will require a standardized manufacturing process to ensure therapeutic safety, reproducibility, and efficacy in age-related conditions. Full article

Krill oil (KO) is a marine-derived nutritional ingredient distinguished by its unique structural composition and increasing relevance in human nutrition, particularly in the context of healthy aging and preservation of intrinsic capacity. Approximately 30–65% of its fatty acids are esterified to phospholipids, a molecular configuration associated with enhanced bioavailability and efficient tissue incorporation of omega-3 polyunsaturated fatty acids, even at relatively low doses. Antarctic krill (Euphausia superba) originates from minimally impacted marine ecosystems, contributing to a favorable safety profile characterized by inherently low levels of environmental contaminants, including heavy metals and persistent organic pollutants. Beyond its structural and safety attributes, KO provides a complex nutrient matrix comprising approximately 25% total n-3 polyunsaturated fatty acids (PUFAs), including ~14% eicosapentaenoic acid (EPA) and ~6.5% docosahexaenoic acid (DHA), together with choline and astaxanthin. This compositional synergy may modulate inflammatory pathways, redox balance, membrane dynamics, and cellular signaling, thereby influencing physiological systems implicated in aging biology. This narrative review critically examines how these distinctive characteristics translate into clinically relevant outcomes supporting the multifunctional applications of KO in human nutrition. The analysis is structured within the framework of intrinsic capacity, encompassing locomotion, vitality, sensory, cognition and psychological dimensions, as a conceptual model for healthy aging. Considerations on bioavailability, tolerability, and sustainability are also discussed in the context of nutritional strategies promoting healthy longevity. Full article

Within the silk manuscript Yizhuan, Confucius underscores the priority of moral righteousness over divination, advocating the cultivation of virtue, benevolence, and righteousness as the proper way to seek auspiciousness and blessing. However, this stance serves merely as a value orientation for the study, application, and interpretation of the Zhouyi. In other words, moral virtue is neither a necessary nor a sufficient condition for divination. In fact, the emergence of the Zhouyi lies in the misalignment and separation between virtue and fortune. The “alignment of virtue and fortune [德福一致]” formed the foundation of the early Western Zhou view of the Mandate of Heaven and served to legitimize the Zhou replacement of the Shang Dynasty. Under this understanding of the Mandate of Heaven, judgments of auspiciousness and inauspiciousness could be made based on the presence or absence of virtue, thereby reducing the relative importance of divination. Confucius’ early attitude toward the Zhouyi reflected this perspective. Nevertheless, the alignment of virtue and fortune could not adequately explain the evident inconsistency between moral conduct and human fate in reality. Consequently, by the late Spring and Autumn period, this framework gradually developed into the notion of “timely mandate” (shiming 時命), which denied a necessary correspondence between virtue and fortune. In response to this shift, the late-life Confucius and his disciples emphasized finding moral and spiritual grounding through virtue, while adopting a calm and accepting attitude toward external circumstances such as success and failure, wealth and poverty, and longevity and premature death. The shift corresponded to the transformation in the conception of the Mandate of Heaven. It was also in this context that Confucius came to value the Zhouyi in his later years. Full article

Caloric restriction (CR), defined as a 30–60% decrease in ad libitum food intake without malnutrition, has emerged as one of the most robust non-pharmacological interventions for promoting metabolic health and longevity in various species, including yeast, worms, flies, rodents, and perhaps non-human primates. In addition, CR has been shown to reduce the incidence of age-related disorders (for example, diabetes, cancer, and cardiovascular disorders) in mammals. Among the key organs influenced by CR, the pancreas—particularly the insulin-producing β-cells—plays a central role in maintaining glucose homeostasis and metabolic balance. A growing body of evidence suggests that CR exerts its beneficial effects, at least in part, through the modulation of nutrient-sensing pathways and epigenetic regulators. Sirtuins, a family of NAD⁺-dependent deacetylases and ADP-ribosyltransferases, have gained attention as pivotal molecular mediators of CR. By responding to changes in cellular energy status, sirtuins regulate diverse processes including gene expression, oxidative stress response, mitochondrial function, and autophagy. In the pancreas, sirtuins such as SIRT1, SIRT3, and SIRT6 have been implicated in preserving β-cell function, enhancing insulin secretion, and protecting against metabolic stress and inflammation. This review critically examines current evidence regarding the role of individual sirtuins in mediating the pancreatic response to caloric restriction, with particular emphasis on β-cell physiology, insulin secretion, mitochondrial function, autophagy, oxidative stress, and inflammatory signaling. We further discuss how these molecular mechanisms contribute to systemic metabolic homeostasis and may influence healthy longevity. Importantly, we integrate experimental findings with emerging clinical evidence demonstrating the recovery of β-cell function following dietary energy restriction and identify current controversies, limitations, and key knowledge gaps that should guide future translational research. Collectively, available evidence suggests that sirtuins represent central molecular links between caloric restriction and β-cell adaptation, highlighting their potential as therapeutic targets for preserving pancreatic function and preventing metabolic disease. Full article

Aging-related decline involves changes in oxidative stress, inflammation, mitochondrial function, telomere maintenance, metabolic regulation, and extracellular matrix homeostasis. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and searched PubMed, Scopus, Embase, and Web of Science for English-language studies published from 1993 to 2025. Twelve primary studies met the eligibility criteria: four randomized clinical studies, four animal studies, one in vitro mechanistic study, and three delivery-system/formulation studies. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2), the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool, and a review-specific domain-based checklist informed by the National Toxicology Program/Office of Health Assessment and Translation framework. Representative compounds, including resveratrol, astragaloside IV, Ganoderma lucidum polysaccharide, epigallocatechin-3-gallate (EGCG) and betulinic acid, were associated with mitochondrial regulation, antioxidant defense, cytoskeletal stability, gut–brain signaling, extracellular-matrix protection, and longevity-related signaling. Nanoliposomes and poly(lactic-co-glycolic acid) (PLGA) nanoparticles improved selected stability, penetration, and pharmacokinetic outcomes. However, the evidence base was heterogeneous and predominantly preclinical; human evidence was limited to four relatively small studies, and certainty ranged from moderate to very low. The findings support mechanistic and translational potential but do not establish definitive anti-aging efficacy in humans. Full article

Chronic low-grade aging-associated inflammation, or inflammaging, is a central pillar of age-related decline in quality of life. Inflammaging is partially mediated by impaired intestinal, immune, and microbiome function, and it has been hypothesized that probiotics could be used to promote healthy aging. SBD121, a defined synbiotic containing food-derived microbial strains and prebiotic fibers, has previously been shown to improve grip strength in male rats, an important indicator of healthspan, and is under evaluation in a clinical trial of 143 newly diagnosed rheumatoid arthritis patients (NCT06005220). However, the mechanisms underlying its potential benefits have not been determined. Here, we examined the function of SBD121 in microbial, cellular, and animal models relevant to inflammaging. SBD121 inhibited the growth of potential microbial pathogens, produced immunomodulatory metabolites in vitro, and improved human intestinal cell barrier function under both basal and challenge conditions, while reducing inflammatory chemokine secretion following inflammatory challenge. SBD121 also reduced the secretion of multiple chemokines in lipopolysaccharide-stimulated human intestinal and immune cells. Finally, SBD121 improved survival and locomotor activity in a C. elegans longevity model, providing evidence of benefits to lifespan and healthspan. Together, these data demonstrate that SBD121 exhibits beneficial microbial, epithelial, immune, and longevity effects and support continued investigation of SBD121 as a candidate intervention for healthy aging. Full article

Wearable robots that can support balance and prevent falls hold great promise to increase the longevity and quality of life of the older population. However, a lack of understanding of human–robot dynamic interactions and users’ reactions to robot interventions can limit the functionality and usability of these robots. A wearable lower-limb robot was developed to study different strategies to proactively prevent falls during obstacle navigation and to investigate human–robot interactions and users’ reactions to different intervention parameters. A novel non-anthropomorphic architecture was designed for robot legs to allow the direct modulation of foot-placement position in the sagittal plane, using only a single active degree of freedom per leg. Three participants completed a series of walking trials wearing the robot, with different levels of robot intervention. The developed robot was able to successfully modify users’ stride length (e.g., 6–12% and 7.5–20% change in step length for 12 Nm robot hip flexion and extension torques, respectively) in the desired direction, indicating the possibility for assisted balance during obstacle navigation through foot-placement modulation. The measurements show that users’ reactions to the robot intervention is subject-specific and time-varying but, in all cases, plays a considerable role in the final movement trajectory. Controllers of the balance assistance robots must take into account the user’s personalized response to different intervention parameters, to improve functionality, efficiency and user comfort. Full article

Population ageing has intensified interest in biological mechanisms that influence healthspan and susceptibility to age-related diseases. Among these mechanisms, the gut microbiota has emerged as an important modulator of immune, metabolic, and neurophysiological processes involved in ageing. This narrative review critically synthesises current evidence regarding age-related alterations in gut microbiota composition and function, their relationship with inflammaging and the hallmarks of ageing, and the potential role of microbiota-targeted interventions in promoting healthy ageing. A comprehensive narrative literature search was conducted using PubMed, Scopus, and Web of Science, focusing primarily on human observational studies, longitudinal cohorts, mechanistic investigations, and interventional trials published in peer-reviewed journals between 2010 and 2025. Priority was given to studies examining older adults, frailty, longevity, and microbiota-mediated mechanisms relevant to ageing biology. Current evidence suggests that ageing is frequently associated with reduced microbial diversity, depletion of beneficial short-chain fatty acid-producing taxa, altered intestinal barrier integrity, and increased abundance of pro-inflammatory microorganisms. These alterations are linked to inflammaging and may contribute to neurodegenerative, cardiovascular, metabolic, musculoskeletal, and joint diseases, including osteoporosis, sarcopenia, rheumatoid arthritis, and osteoarthritis. However, causality remains incompletely established in humans, and substantial inter-individual variability exists. Studies of centenarians suggest that preservation of specific microbial metabolic functions may be associated with healthier ageing trajectories. Dietary interventions, particularly Mediterranean-style diets rich in fibre and polyphenols, alongside exercise, prebiotics, probiotics, and emerging microbiota-targeted therapies, show potential to modulate these pathways. Despite significant advances, major challenges remain regarding causality, reproducibility, standardisation of microbiome analyses, and personalised therapeutic implementation. Future longitudinal multi-omics studies and precision microbiome interventions will be essential to clarify the translational role of the gut microbiota in healthy ageing and age-related disease prevention. Full article

Oocyte aging is a conserved biological process that limits reproductive success across animal taxa. While most research has focused on mammalian systems, particularly humans, comparative studies reveal both shared molecular mechanisms and lineage-specific adaptations that shape oocyte longevity. Here, we synthesise current knowledge on chromosomal instability, mitochondrial dysfunction, proteostasis collapse and epigenetic alterations, integrating insights from insects, nematodes and vertebrates. We argue that these phenomena should not be viewed as independent hallmarks of reproductive aging but rather as interconnected manifestations of a progressive decline in cellular quality control networks. By comparing taxa, we identify both conserved vulnerabilities, including cohesin loss, mitochondrial deterioration and genome instability, and lineage-specific adaptations that mitigate their effects. We further propose the hypothesis that biomolecular condensates, including the Balbiani body, nuage and recently described endolysosomal assemblies, may function as higher-order organizational hubs coordinating mitochondrial quality control, proteostasis and genome defence. This perspective provides a unifying framework for understanding oocyte aging as a systems-level process and highlights new directions for future studies of reproductive longevity. Full article

Camellia japonica L. (Theaceae) seed oil is an essential component for skin protection, attributed to its antioxidant properties and anti-aging effects. In this study, Camellia japonica seed oil underwent fermentation with Sporidiobolus pararoseus (Fell & Tallman, CGMCC No. 39106, commercial name: Longevity yeast of 1021-year-Camellia japonica). The post-fermented oil, designated Longevity Yeast Oil (LYO), was used in the present research. Gas chromatography–mass spectrometry analysis demonstrated that methyl esterification of LYO afforded twelve fatty acid methyl esters. We used an aging model in human epidermal keratinocytes and human skin fibroblasts exposed to ultraviolet B (UVB) to explore the anti-skin aging effects and mechanisms of LYO. The results of the CCK-8 assay demonstrated that LYO exhibited no cytotoxicity but instead displayed potential proliferative activity, indicating its excellent safety profile. Quantitative real-time polymerase chain reaction analyses confirmed that LYO downregulated the expression of autophagy marker p62 and upregulated LC3B, thereby activating the autophagic pathway. Further investigation revealed that LYO protected against UVB-induced apoptosis, promoted the synthesis of collagen and elastin, and upregulated the expression of loricrin, filaggrin, and ceramides, effectively reversing UVB-induced skin cellular aging. Notably, we further revealed that LYO alleviated UVB-induced cutaneous photoaging via activating cellular autophagy pathway. In conclusion, LYO demonstrated biocompatibility and conferred protection to skin cells against photoaging, thereby establishing a theoretical basis for the development of innovative autophagy-targeted anti-aging therapies. Full article

Aging is a major risk factor for numerous chronic diseases and a leading contributor to global mortality. Slowing the rate of aging would have revolutionary implications for health and longevity. A fundamental barrier to achieving this goal, however, is the difficulty of accurately measuring the effects of rejuvenating interventions. The development of precise gerontometric methods, therefore, is a priority for both science and preventive medicine. In this opinion article, the authors suggest the principles and discuss the implementation of precision gerontometry using recent advances in metabolomics. Although metabolomic approaches have limited accuracy in determining biological age, the described approach, which averages multiple metabolites from a large metabolomic signature of aging, circumvents this limitation. It allows for measurement of biological age change with an accuracy of approximately one month. Such precision gerontometry enables accelerated testing of candidate anti-aging interventions, helping to eliminate ineffective ones, speed the development of effective ones, and ultimately extend the duration of healthy human life, with profound social and humanitarian benefits. Full article

Youth experiencing homelessness and housing instability (YEH) face disproportionate health risks and structural barriers to health equity, which were intensified during the COVID-19 pandemic. We conducted a community-based participatory research study with 21 adolescents (ages 13–17) and transitional-aged youth (ages 18–26) experiencing homelessness or housing instability in San Diego, California, USA. Between February and July 2023, we conducted six “arts-based engagement sessions” (5 in English, 1 in Spanish) that blended expressive arts and focus group approaches to examine how YEH accessed, evaluated, and applied health information, and how trust and material and structural resource constraints shaped engagement with COVID-19 information and prevention guidance. We analyzed data via applied thematic analysis. Participants described how COVID-19 restrictions and economic disruption amplified pre-existing housing precarity, worsening material conditions and mental health. Participants selectively trusted COVID-19 information based on who provided it, how credible it felt, and whether it aligned with their lived experiences. Community-based providers and, for some, churches and cultural or ancestral knowledge were key information sources. Trust in government and public health messaging was conditional and shaped by perceptions of credibility, coherence, and political motivation. Participants described information overload and rapidly changing guidance as overwhelming and often incompatible with their material realities, leading to disengagement, reliance on intuition, or deprioritization of prevention behaviors. Effective communication during future health emergencies must center trusted relational messengers, align guidance with lived realities, and address the structural conditions that shape whether health information can be meaningfully acted upon. Full article

Background/Objectives: Stem cells with the ability to differentiate into other cell types and self-renewal afford a powerful apparatus for the healthcare system to replace and rejuvenate damaged tissues and organs in the treatment of various diseases. For the last few decades, stem cell therapy (SCT) has evolved from being an experimental approach to a recognized clinical treatment. SCT and regenerative medicine have garnered tremendous attention and become prominent tools, especially in treating chronic and acute disease and addressing organ failures, and in their repair and replacement, which are directly associated with human health, life, and longevity. Methods: In this review, after providing a brief history and need for the SCT, the employed delivery techniques utilizing various biomaterials, as well as recent developments in nanotechnological methods, are presented. It is focused on the current literature for the recent progress of stem cell therapy and tissue engineering for the application fields in neurological, ophthalmological, cardiovascular, orthopedic, and oncology, followed by the challenges associated with their applications. Results: In addition to safety concerns, challenges such as uncontrollable differentiations, genetic and epigenetic instability, limited cell survival and integration, immunological rejections, scaling and manufacturing drawbacks, as well as unpredictable behaviors and clinical limitations were reviewed. Conclusions: Future aspects with respect to regenerative medicine and tissue engineering, gene editing and personalized therapies, immunomodulation and anti-inflammatory applications, as well as neuroregeneration and treatment of neurodegenerative disorders are reflected. Full article

Alkaline water is increasingly marketed for musculoskeletal and recovery benefits, yet its relevance to healthy aging, sarcopenia prevention, and functional capacity in older adults remains largely unexplored. This systematic evidence map and translational appraisal examined whether the available comparative human evidence on alkaline water is applicable to aging populations and longevity research. Following PRISMA guidance, PubMed and Scopus were searched from January 2005 to September 2025. Eligible studies were controlled or comparative observational human studies reporting muscle strength, physical performance, or recovery outcomes. Risk of bias was assessed using RoB 2, ROBINS-I, and JBI criteria; evidence certainty was judged narratively using GRADE-informed principles. Ten studies met the inclusion criteria. Most enrolled young athletic populations; only two had partial relevance to aging cohorts. Crucially, no study included participants aged 65 years or older or assessed primary sarcopenia-relevant endpoints such as appendicular lean mass, gait speed, or chair-rise performance; this total absence of data in the target demographic represents the central limitation of the current literature. Risk of bias ranged from some concerns to serious. The most consistent signals were short-term improvements in lactate clearance and perceived exertion in young male athletes. Evidence for strength, functional performance, and safety in older adults was absent or indirect. Current evidence, rated low to very low certainty for aging-relevant outcomes, does not support alkaline water as an evidence-based strategy for healthy aging or muscle preservation in older adults. Age-appropriate trials using EWGSOP2-aligned outcomes are urgently needed. Full article

Background: The relationship between physical exercise and human longevity constitutes one of the most consequential intersections in contemporary preventive medicine. Although international guidelines recommend 150 min of moderate-intensity exercise weekly, growing evidence suggests that the architecture of optimal exercise is far more complex, encompassing dose, modality, timing across the lifespan, and the paradox risks imposed by extreme endurance. Methods: We included in this narrative review landmark cohort studies, randomized controlled trials, meta-analyses, and expert physiological frameworks published in high-impact cardiovascular, sports medicine, and longevity journals from 1966 to 2024. Results: Cardiorespiratory fitness (CRF), indexed by maximal oxygen uptake (VO₂ max), demonstrates the strongest and most linear dose–response relationship with all-cause mortality identified in preventive medicine, with every 1 metabolic equivalent of task (MET) increment associated with a 12–15% reduction in mortality risk. The optimal dose of vigorous-intensity exercise follows a J-shaped dose–response curve: 3–5 sessions per week generating 1–2.4 h of vigorous activity is associated with the lowest all-cause mortality risk in large prospective cohorts, whereas chronic extreme endurance exercise incurs measurable atrial remodeling, patchy myocardial fibrosis, and a 5.3-fold increase in the risk of atrial fibrillation. The importance of exercise types shifts profoundly across the lifespan, transitioning from aerobic capacity effort in the third decade to resistance training in the seventh decade and neuromuscular stability in the eighth. Based on our interpretation of the available evidence, we propose a structured, personalized four-step exercise pathway integrating CRF assessment, lifespan-adapted prescription, lifestyle co-interventions, and periodic reassessment. Conclusions: Among currently available lifestyle interventions, regular exercise is consistently associated with some of the largest and most reproducible reductions in all-cause and cardiovascular mortality observed in prospective cohort data, while remaining accessible and cost-effective. Full article