Search Results (239)

Background and Objectives: Peri-implantitis is a biologically driven complication that jeopardizes dental implant longevity. While chemical decontamination is frequently employed as an adjunct to mechanical debridement, its impact on implant surface integrity and cellular compatibility remains insufficiently defined. This study aimed to evaluate the effects of several chemical agents used in peri-implantitis treatment on the surface morphology and potential biocompatibility of titanium dental implants. Materials and Methods: Twenty-five Ti6Al4V implants were exposed to one of the following agents: saline solution, 3% hydrogen peroxide, 40% citric acid, 17% EDTA, and a mixture (1:1) of citric (2%) and phosphoric (1N) acids. This in vitro study employed a 7-day immersion protocol to accentuate surface effects under controlled laboratory conditions, acknowledging that clinical exposures are substantially shorter. Surface topography was evaluated by Atomic Force Microscopy, while cellular response and corrosion products were assessed using Scanning Electron Microscopy. Surface roughness parameters were statistically analyzed. Results: Hydrogen peroxide induced selective corrosion of the β phase and formed a compact passivation layer that supported mesenchymal stem cell adhesion. Citric acid etched grain boundaries, producing localized roughness that also permitted cell proliferation. EDTA caused advanced grain dissolution and debris accumulation, increasing surface roughness but impairing cellular adhesion. The citric–phosphoric acid mixture led to the highest roughness values and visible corrosion debris. In all cases, macrostructural integrity of the implants was preserved. Conclusions: Chemical agents used in peri-implantitis treatment induce distinct surface alterations on titanium implants. Controlled use of hydrogen peroxide and citric acid may enhance surface biocompatibility, while aggressive protocols such as EDTA and acid combinations require caution due to their adverse effects on surface morphology and cellular response. These findings may inform the development of optimized decontamination protocols for clinical management of peri-implantitis. Full article

The process of aging is fundamentally driven by genomic instability and the accumulation of DNA damage, which progressively impair cellular and tissue function. In order to counteract these challenges, cells rely on the DNA damage response (DDR), a multilayered signaling and repair network that preserves genomic integrity and sustains homeostasis. Within this framework, nucleases and helicases have pivotal and complementary roles by remodeling aberrant DNA structures, generating accessible repair intermediates, and determining whether a cell achieves faithful repair, undergoes apoptosis, or enters senescence. Defects in these enzymes are exemplified in human progeroid syndromes, where inherited mutations lead to premature aging phenotypes. This phenomenon is also replicated in genetically engineered mouse models that exhibit tissue degeneration, stem cell exhaustion, and metabolic dysfunction. Beyond their canonical repair functions, helicases and nucleases also interface with the epigenome, as DNA damage-induced chromatin remodeling alters enzyme accessibility, disrupts transcriptional regulation, and drives progressive epigenetic drift and chronic inflammatory signaling. Moreover, their dysfunction accelerates the exhaustion of adult stem cell populations, such as hematopoietic, neural, and mesenchymal stem cells. As a result, tissue regeneration is undermined, establishing a self-perpetuating cycle of senescence, impaired repair, and organismal aging. Current research is focused on developing therapeutic strategies that target the DDR–aging axis on several fronts: by directly modulating repair pathways, by regulating the downstream consequences of senescence, or by preventing DNA damage from accumulating upstream. Taken together, evidence from human disease, animal models, molecular studies, and pharmacological interventions demonstrates that nucleases and helicases are not only essential for genome maintenance but also decisive in shaping aging trajectories. This provides valuable knowledge into how molecular repair pathways influence organismal longevity and age-related diseases. Full article

Skeletal muscle is increasingly recognized as a dynamic endocrine organ whose secretome—particularly myokines—serves as a central hub for the coordination of systemic metabolic health, inflammation, and tissue adaptation. This review integrates molecular, cellular, and physiological evidence to elucidate how myokine signaling translates mechanical and metabolic stimuli from exercise into biochemical pathways that regulate glucose homeostasis, lipid oxidation, mitochondrial function, and immune modulation. We detail the duality and context-dependence of cytokine and myokine actions, emphasizing the roles of key mediators such as IL-6, irisin, SPARC, FGF21, and BAIBA in orchestrating cross-talk between muscle, adipose tissue, pancreas, liver, bone, and brain. Distinctions between resistance and endurance training are explored, highlighting how each modality shapes the myokine milieu and downstream metabolic outcomes through differential activation of AMPK, mTOR, and PGC-1α axes. The review further addresses the hormetic role of reactive oxygen species, the importance of satellite cell dynamics, and the interplay between anabolic and catabolic signaling in muscle quality control and longevity. We discuss the clinical implications of these findings for metabolic syndrome, sarcopenia, and age-related disease, and propose that the remarkable plasticity of skeletal muscle and its secretome offers a powerful, multifaceted target for lifestyle interventions and future therapeutic strategies. An original infographic is presented to visually synthesize the complex network of myokine-mediated muscle–organ interactions underpinning exercise-induced metabolic health. Full article

The fruits of Piper longum L. (long pepper), a spice and medicinal plant of the family Piperaceae, are widely used in South and Southeast Asian cuisine and traditional medicine, valued for their pungent flavor and aroma. The metabolomic profiling of P. longum using UPLC-qTOF-MS/MS provided a comprehensive chemical characterization of this traditional medicinal plant, revealing that lignans and amide alkaloids are the major classes of secondary metabolites. To further investigate its pharmacological potential, the bioactive ethyl acetate fraction was subjected to a SIRT1-targeted chemical investigation. This led to the isolation and structural elucidation of three previously undescribed compounds, a cadinene-type sesquiterpene (1) and two oxo-neolignan (2 and 5), along with four known compounds 3, 4, 6, and 7. Compounds (1–7) were evaluated for their ability to modulate p53-dependent transcriptional activity via SIRT1 activation using a luciferase reporter cell-based assay. SIRT1, a NAD⁺-dependent deacetylase, is a crucial regulator of longevity, metabolism, and cellular stress resistance, making it a key target for the treatment of age-related diseases. Compounds 2–7 exhibited significant SIRT1 activation, with compound 6 displaying particularly high efficacy, comparable to resveratrol, the most well-known natural SIRT1 activator. This study demonstrates that the discovery of novel chemical scaffolds through bioactivity-guided screening highlights the value of combining advanced metabolomics with pharmacological evaluation. The results support the traditional medicinal use of long pepper and its potential for development into functional foods or pharmaceuticals for healthy aging. Full article

Metformin, an oral antihyperglycemic drug, represents the cornerstone of pharmacological treatment for type 2 diabetes mellitus (T2DM). Its primary glucose-lowering effects are well established, predominantly mediated through the activation of AMP-activated protein kinase (AMPK). This activation leads to a reduction in hepatic glucose production (primarily by inhibiting gluconeogenesis and glycogenolysis) and an increase in peripheral glucose uptake and utilization. Beyond its direct impact on glucose metabolism, metformin also improves insulin sensitivity and has beneficial effects on lipid profiles. Increasingly, research shows that metformin has pleiotropic effects. In addition to its recognized antihyperglycemic action, metformin is emerging as a regulator of cellular processes implicated in aging. Indeed, emerging evidence suggests a potential role of metformin in modulating pathways associated with longevity and ameliorating the symptoms of age-related diseases, including neurodegenerative disorders (such as Alzheimer’s and Parkinson’s diseases), cardiovascular diseases, age-related macular degeneration, and osteoporosis. The proposed mechanisms for these broader effects involve AMPK activation, modulation of the mTOR pathway, reduction of oxidative stress, and promotion of autophagy. After exploring the established role of metformin in T2D, this review provides a comprehensive investigation of its promising applications in the context of age-related diseases, offering valuable insights into its multifaceted therapeutic potential beyond glycemic control. Full article

Sirtuins (SIRT1–SIRT7) are NAD⁺-dependent deacetylases that link cellular energy status to chromatin maintenance, mitochondrial function and inflammatory signaling. While modulation of SIRT1, SIRT3 and SIRT6 extends lifespan in model organisms, evidence in extreme-age humans is scarce. We quantified protein and mRNA levels, and protein-to-mRNA ratios for SIRT1, SIRT3 and SIRT6 in buccal epithelial cells obtained from healthy young adults, middle/late-aged individuals and nonagenarians/centenarians residing in a longevity-enriched region of south-eastern Azerbaijan. The cohort comprised 23 participants, stratified by sex and cardiovascular disease (CVD) status (5 per sex/CVD subgroup). This design allows us to: (1) define a baseline “sirtuin profile” of healthy longevity, (2) evaluate the impact of CVD as a prevalent age-related pathology, and (3) explore potential sex-specific modulation. These findings establish an initial human framework linking sirtuin translational control to healthy ageing and cardiovascular health. Full article

Polyamines, particularly spermidine, have emerged as key dietary factors with roles in cellular health, autophagy, and longevity. However, strategies for scalable production of polyamine-rich food ingredients remain limited. Here, we report the development of a high-spermidine-producing Saccharomyces cerevisiae strain, 3L63, obtained via ultraviolet mutagenesis of the K7 strain. This strain exhibited a 5.9-fold increase in the total polyamine content, with spermidine being the most abundant. A scalable fermentation system of up to 10⁴ L was established, yielding a dried yeast product that met food safety criteria. Whole-genome sequencing identified mutations in central metabolic pathways, including ARG3, and functional enrichment analysis suggested broad metabolic rewiring, supporting an enhanced biosynthetic capacity, including polyamines. Free amino acid profiling revealed higher arginine levels in 3L63 than in K7, which is consistent with its role as a polyamine precursor. The 3L63 yeast-derived product was enriched in essential amino acids and polyamines. Functionally, this strain promoted the proliferation of normal and senescent human dermal fibroblasts, and its autophagy-inducing activity exceeded that of equivalent concentrations of pure spermidine, suggesting synergistic effects of yeast-derived bioactive compounds. This study demonstrates a non-genetically modified, high-spermidine yeast strain as a promising functional food ingredient with potential applications in healthy aging. Full article

Background/Objectives: Telomeres and the enzyme telomerase play essential roles in cellular aging and cardiovascular health. Physical activity is thought to influence telomere dynamics via upregulation of the hTERT gene, which encodes the catalytic subunit of telomerase. However, data on this relationship in middle-aged endurance athletes remain limited. This study aimed to investigate the association between long-term endurance training, cardiac structural adaptations, and hTERT gene expression in middle-aged elite athletes. Methods: A total of 38 middle-aged elite runners and 37 age-matched sedentary controls were enrolled. Echocardiographic assessments, VO₂peak measurements, and hTERT gene expression analysis using RT-PCR were conducted. Left ventricular mass (LVM), wall thicknesses, and cardiac volumes were compared, and correlations with hTERT expression were analyzed. Results: Athletes demonstrated significantly higher VO₂peak and echocardiographic parameters including LVEDD, LV mass, and wall thicknesses (p < 0.05). hTERT gene expression was 2.06-fold higher in athletes compared to controls. Significant positive correlations were observed between hTERT expression and VO₂peak, LVM, LV wall thicknesses, and right ventricular parameters. Conclusions: These findings suggest that regular aerobic exercise may contribute to both improved cardiovascular performance and cellular longevity by enhancing telomerase-related mechanisms. Full article

Background: Cutaneous aging is a multifactorial process, increasingly understood through the lens of cellular senescence, a state of stable cell cycle arrest accompanied by a pro-inflammatory secretory phenotype that disrupts tissue homeostasis. Recent research has highlighted the accumulation of senescent dermal fibroblasts as a key contributor to age-related skin changes, including loss of elasticity, collagen degradation, and impaired regeneration. Objective: This review explores the emerging hypothesis that energy-based devices (EBDs), particularly lasers, may act as senotherapeutic tools by targeting cellular senescence pathways in aging skin. We examine the molecular and histological effects of laser therapy in relation to known biomarkers of senescence and evaluate their potential role in regenerative dermatology. Methods: We conducted a review of published studies on fractional lasers, red-light therapies, and other EBDs, focusing on their impact on fibroblast activity, extracellular matrix remodeling, and senescence-associated markers such as p16^INK4a, p21^Cip1, telomerase, and SASP-related cytokines. Comparative analysis with pharmacologic senotherapeutics was also performed. Results: Preclinical and clinical data suggest that specific EBDs can modulate dermal aging at the molecular level by enhancing mitochondrial activity, increasing type III collagen synthesis, reducing senescence-related gene expression, and promoting fibroblast turnover. In contrast to systemic senolytics, lasers provide localized and titratable interventions with a favorable safety profile. Conclusions: Energy-based devices, particularly fractional lasers and red-light systems, hold promise as non-invasive senotherapeutic interventions in dermatology. By modulating senescence-associated pathways, EBDs may offer not only cosmetic improvement but also biological rejuvenation. Further mechanistic studies and biomarker-based trials are warranted to validate this paradigm and refine treatment protocols for longevity-oriented skin therapies. Full article

Ovarian aging is characterized by a gradual decline in both reproductive and endocrine functions, ultimately culminating in the cessation of ovarian activity around the age of 50, when most women experience natural menopause. The decline begins early, as follicular attrition is initiated in utero and continues throughout childhood and reproductive life. Most follicles undergo atresia without progressing through substantial stages of growth. With increasing age, a pronounced reduction occurs in the population of resting follicles within the ovarian reserve, accompanied by a decline in the size of growing follicular cohorts. Around the age of 38, the rate of follicular depletion accelerates, sometimes resulting in diminished ovarian reserve (DOR). The subsequent menopausal transition involves complex, irregular hormonal dynamics, manifesting as increasingly erratic menstrual patterns, primarily driven by fluctuations in circulating estrogens and a rising incidence of anovulatory cycles. In parallel with the progressive depletion of the follicular pool, the serum concentrations of anti-Müllerian hormone (AMH) decline gradually, while reductions in inhibin B levels become more apparent during the late reproductive years. The concomitant decline in both inhibin B and estrogen levels leads to a compensatory rise in circulating follicle-stimulating hormone (FSH) concentrations. Together, these endocrine changes, alongside the eventual exhaustion of the follicular reserve, converge in the onset of menopause, which is defined by the absence of menstruation for twelve consecutive months. The mechanisms contributing to ovarian aging are complex and multifactorial, involving both the oocyte and the somatic cells within the follicular microenvironment. Oxidative stress is thought to play a central role in the age-related decline in oocyte quality, primarily through its harmful effects on mitochondrial DNA integrity and broader aspects of cellular function. Although granulosa cells appear to be relatively more resilient, they are not exempt from age-associated damage, which may impair their hormonal activity and, given their close functional relationship with the oocyte, negatively influence oocyte competence. In addition, histological changes in the ovarian stroma, such as fibrosis and heightened inflammatory responses, are believed to further contribute to the progressive deterioration of ovarian function. A deeper understanding of the biological processes driving ovarian aging has facilitated the development of experimental interventions aimed at extending ovarian functionality. Among these are the autologous transfer of mitochondria and stem cell-based therapies, including the use of exosome-producing cells. Additional approaches involve targeting longevity pathways, such as those modulated by caloric restriction, or employing pharmacological agents with geroprotective properties. While these strategies are supported by compelling experimental data, robust clinical evidence in humans remains limited. Full article

Dermal fibroblasts, the primary stromal cells of the dermis, exhibit remarkable plasticity in response to various stimuli, playing crucial roles in tissue homeostasis, wound healing, and ECM production. This study examines the molecular mechanisms underlying fibroblast plasticity, including key signaling pathways, epigenetic regulation, and microRNA-mediated control. The impact of aging on ECM synthesis and remodeling is discussed, and the diminished production of vital components such as collagen, elastin, and glycosaminoglycans are highlighted, alongside enhanced ECM degradation through upregulated matrix metalloproteinase activity and accumulation of advanced glycation end products. The process of cellular senescence in dermal fibroblasts is explored, with its role in skin aging and its effects on tissue homeostasis and repair capacity being highlighted. The senescence-associated secretory phenotype (SASP) is examined for its contribution to chronic inflammation and ECM disruption. This review also presents therapeutic perspectives, focusing on senolytics and geroprotectors as promising strategies to combat the negative effects of fibroblast senescence. Current challenges in translating preclinical findings to human therapies are addressed, along with future directions for research in this field. This comprehensive review explores the complex interplay between dermal fibroblast plasticity, cellular senescence, and extracellular matrix (ECM) remodeling in the context of skin aging. In conclusion, understanding the complex interplay between dermal fibroblast plasticity, cellular senescence, and extracellular matrix (ECM) remodeling is essential for developing effective anti-aging interventions, which highlights the need for further research into senolytic and geroprotective therapies to enhance skin health and longevity. This approach has shown promising results in preclinical studies, demonstrating improved skin elasticity and reduced signs of aging. Full article

The paradigm-shift idea of murburn concept is no hypothesis but developed directly from fundamental facts of cellular/ecological existence. Murburn involves spontaneous and stochastic interactions (mediated by murzymes) amongst the molecules and unbound ions of cells. It leads to effective charge separation (ECS) and formation/recruitment of diffusible reactive species (DRS, like radicals whose reactions enable ATP-synthesis and thermogenesis) and emission of radiations (UV/Vis to ELF). These processes also lead to a chemo-electromagnetic matrix (CEM), ascertaining that living cell/organism react/function as a coherent unit. Murburn concept propounds the true utility of oxygen: generating DRS (with catalytic and electrical properties) on the way to becoming water, the life solvent, and ultimately also leading to phase-based macroscopic homeostatic outcomes. Such a layout enables cells to become simple chemical engines (SCEs) with powering, coherence, homeostasis, electro-mechanical and sensing–response (PCHEMS; life’s short-term “intelligence”) abilities. In the current review, we discuss the coacervate nature of cells and dwell upon the ways and contexts in which various radiations (either incident or endogenously generated) could interact in the new scheme of cellular function. Presenting comparative evidence/arguments and listing of systems with murburn models, we argue that the new perceptions explain life processes better and urge the community to urgently adopt murburn bioenergetics and adapt to its views. Further, we touch upon some distinct scientific and sociological contexts with respect to the outreach of murburn concept. It is envisaged that greater awareness of murburn could enhance the longevity and quality of life and afford better approaches to therapies. Full article

This comment focuses on the contribution of experimental brain ischemia to the overwhelming incidence of Alzheimer’s disease in women as presented by Lohkamp et al. in Life 2025, 15, 333. The authors showed that in Alzheimer’s disease and ischemic stroke there are sex-dependent adaptations in the form of cross-links and vice versa. It was emphasized that the high longevity of women in itself does not explain the mechanisms underlying the biological differences between the sexes causing a female predominance in the development of Alzheimer’s disease. Differences were demonstrated between males and females: female APP/PS1 mice had greater amyloid deposition, hyperactivity, lower body weight, and reduced cerebral blood flow, as well as less neuroinflammation, which the authors suggest may have potential neuroprotection. It should be noted that some of the information presented in the article by Lohkamp et al. raises more questions than answers. Therefore, future studies should consider, for example, studies using single-cell technologies that can provide insight into the timing and sequence of cellular dysfunctions across sexes and analyze the continuity of changes over time, starting from short-term observations of a few days and ending with long-term observations of a year or more, to assess the continuity and differentiation of changes. Full article

Aging is a complex biological process marked by a progressive decline in cellular function, leading to age-related diseases such as neurodegenerative disorders, cancer, and cardiovascular diseases. Despite significant advancements in aging research, finding effective interventions to decelerate aging remains a challenge. This review explores microgravity as a novel therapeutic approach to combat aging and promote healthy longevity. The hallmarks of aging, including genomic instability, telomere shortening, and cellular senescence, form the basis for understanding the molecular mechanisms behind aging. Interestingly, microgravity has been shown to accelerate aging-like processes in model organisms and human tissues, making it an ideal environment for studying aging mechanisms in an accelerated manner. Spaceflight studies, such as NASA’s Twins Study and experiments aboard the International Space Station (ISS), reveal striking parallels between the physiological changes induced by microgravity and those observed in aging populations, including muscle atrophy, bone density loss, cardiovascular deconditioning, and immune system decline in a microgravity environment. However, upon microgravity recovery, cellular behavior, gene expression, and tissue regeneration were seen, providing vital insights into aging mechanisms and prospective therapeutic approaches. This review examines the potential of microgravity-based technologies to pioneer novel strategies for decelerating aging and enhancing healthspan under natural gravity, paving the way for breakthroughs in longevity therapies. Full article

Plant polyphenols have emerged as potent bioactive molecules that can modulate key cellular pathways associated with aging and chronic disorders. The Mediterranean diet and the traditional Japanese style of life are rich in polyphenol-containing foods and beverages, and epidemiological evidence links these dietary patterns to increased longevity and reduced morbidity. This narrative review examines the chemical description of plant polyphenols, their mechanisms of action, including anti-inflammatory, antioxidant, and hormetic effects, and how supplementation or a diet rich in these compounds may provide further life extension. We discuss the major classes of polyphenols present in the Mediterranean dietary pattern (e.g., resveratrol and hydroxytyrosol) and in the Japanese diet (e.g., epigallocatechin gallate and soy isoflavones), comparing their biological behaviors and cooperative effects on metabolic, cardiovascular, and neurodegenerative conditions. We also examine a few preclinical and clinical studies that explain the beneficial impact of these chemicals on aging-associated biomarkers. Furthermore, both dietary habits are characterized by low consumption of processed foods and sugary carbonated drinks and reduced utilization of deep-frying with linoleic acid-rich oils, a practice that reduces the formation of harmful lipid peroxidation products, notably 4-hydroxynonenal, known to be implicated in accelerating the aging process. The Mediterranean dietary pattern is also characterized by a low/moderate daily consumption of wine, mainly red wine. This work debates emerging evidence addressing issues of bioavailability, dosage optimization, and formulation technologies for polyphenol supplementation, also comparing differences and similarities with the vegan and vegetarian diets. We also explore how these chemicals could modulate epigenetic modifications that affect gene expression patterns pertinent to health and aging. In conclusion, we aim to show a consolidated framework for the comprehension of how plant polyphenols could be utilized in nutritional strategies for potentiating life expectancy while stimulating further research on nutraceutical development. Full article