Search Results (478)

Osteoporosis can increase the risk of fracture in elderly patients, and insufficient control affects quality of life. Rikkunshi-To (RKT) has been prescribed for elderly patients to improve gastrointestinal function. We postulated that RKT has preventive potential for the development of osteoporosis. Thus, we developed a simple method to evaluate osteoporosis using a continuous series of X-ray images of femurs in mice, and investigated the effects of RKT on the development of osteoporosis in these mice. Male senescence-accelerated mouse strain P6 (SAMP6) mice, a model of senile osteoporosis in humans, were fed diets with or without RKT (1%). We collected X-ray images of the whole body of each mouse weekly and measured the ratio of cortical thickness of the femur (C/F index). The C/F index in SAMP6 mice fed the normal diet was increased between 50 and 80 days old, but it was significantly decreased after 120 days old. On the other hand, the C/F index in SAMP6 mice fed the RKT diet was increased between 50 and 80 days old; however, it remained unchanged throughout the experimental period. We also confirmed that the C/F index in SAMP6 mice fed the RKT diet suddenly decreased on the replacement of the RKT diet with a normal diet, suggesting that we can collect data related to a series of continuous changes in bone mass, and that RKT is useful for the prevention of osteoporosis. Full article

Numerous epidemiological studies indicate that populations exposed to environmental toxicants such as heavy metals have a higher likelihood of developing Alzheimer’s disease (AD) compared to those unexposed, indicating a potential association between heavy metals exposure and AD. The aim of this review is to summarize contemporary mechanistic research exploring the associations of four important metals, arsenic (As), manganese (Mn), lead (Pb), and cadmium (Cd), with AD and possible pathways, processes, and molecular mechanisms on the basis of data from the most recent mechanistic studies. Primary research publications published during the last decade were identified via a search of the PubMed Database. A thorough literature search and final screening yielded 45 original research articles for this review. Of the 45 research articles, 6 pertain to As, 9 to Mn, 21 to Pb, and 9 to Cd exposures and AD pathobiology. Environmental exposure to these heavy metals induces a wide range of pathological processes that intersect with well-known mechanisms leading to AD, such as oxidative stress, mitochondrial dysfunction, protein aggregation, neuroinflammation, autophagy dysfunction, and tau hyperphosphorylation. While exposure to single metals shares some affected pathways, certain effects are unique to specific metals. For instance, Pb disrupts the blood–brain barrier (BBB) and mitochondrial functions and alters AD-related genes epigenetically. Cd triggers neuronal senescence via p53/p21/Rb. As disrupts nitric oxide (NO) signaling, cortical, and synaptic function. Mn causes glutamate excitotoxicity and dopamine neuron damage. Our review provides a deeper understanding of biological mechanisms showing how metals contribute to AD. Information regarding the potential metal-induced toxicity relevant to AD may help us develop effective therapeutic AD intervention, treatment, and prevention. Full article

Though not specifically designed for cancer therapy, several FDA-approved drugs such as metformin, aspirin, and simvastatin have an effect in lowering the incidence of cancer. However, there is a great discrepancy between in vitro concentrations needed to eliminate cancer cells and the plasma concentration normally tolerated within the body. At present, there is no universal explanation for this discrepancy and several mechanisms have been proposed including targeting cancer stem cells (CSCs) or cellular senescence. CSCs are cells with the ability of self-renewal and differentiation known to be resistant to chemotherapy. Senescence is a response to damage and stress, characterized by permanent cell-cycle arrest and apoptotic resistance. Although, for both situations, there are few examples where low concentrations of the FDA-approved drugs were the most effective, there is no satisfactory data to support that either CSCs or cellular senescence are the target of these drugs. In this review, we concisely summarize the most used FDA-approved drugs for non-cancer conditions as well as their potential mechanisms of action in lowering cancer incidence. In addition, we propose that prolonged low-dose administration (PLDA) of specific FDA-approved drugs can be useful for effectively preventing metastasis formation in selected patients. Full article

Several studies have suggested that adiponectin is an anti-aging molecule based on its potential involvement of adipose tissue in skin aging. In this study, we investigated the anti-photoaging efficacy of an adiponectin expression-stimulating peptide derivative, pentasodium tetracarboxymethyl hexanoyl dipeptide-12 (PTHD-12), in in vitro and ex vivo human skin explant models. A double-blind, randomized, comparator placebo-controlled study was performed to confirm clinical efficacy. After irradiation with 50 mJ/cm² of UVB, a UV-induced decrease in adiponectin expression and an increase in inflammatory cytokines in cultured human dermal fibroblasts were prevented by the PTHD-12 treatment test peptide. Mitigation of cellular senescence and senescence-associated secretory phenotype (SASP) expressions induced by UVB (50 mJ/cm²) exposure were also mitigated by the post-treatment of PTHD-12, which was also observed in an ex vivo human skin explant model. The restoration of filaggrin, loricrin, and claudin-1 protein expression in a cultured human skin explant was observed. A clinical study further confirmed that the restoration of UVB-induced skin damage, represented by increased skin redness and trans-epidermal water loss, was accelerated by the use of test peptide PTHD-12-containing products. These results suggest that targeting adiponectin may be a plausible strategy for the development of anti-aging ingredients. Full article

Background/Objectives: Immunosenescence implies innate and adaptive immunity dysfunction, which naturally occurs with aging. It is a complex multifactorial process which can be triggered by either genetic changes, immune changes or both. Numerous research studies have shown that the process of senescence goes alongside chronic immune activation. The purpose of this study is to analyze the changes in the expression of genes associated with adaptive and innate immune responses in order to identify reliable biomarkers for immune aging. Methods: For that aim, 55 clinically healthy individuals of active age (21–65 years) were distributed based on immunophenotyping in two groups, with and without signs of premature senescence. A gene expression analysis was subsequently made on those two groups, and the differentially expressed genes were presented and interpreted. Results: Altogether, forty-eight (48) genes exhibited differential expression between the two groups, most of which showed up-regulation (45) (fold change more than 2), and only three were down-regulated (fold change less than −2). The highest positive fold change showed IL-1β (10.76), BCL6 (13.25) and CCL4 (15.91), while the highest negative fold changes were documented for IL23R (−3.10), IL5 (−2.66) and PTGS2 (COX-2) (−2.15). Conclusions: Our results reveal that immunosenescence is positively associated with chronic inflammation, which is typical for the aging process. On the other hand, we identified markers of possible protective effects against oxidative stress and tumorigenesis. These findings can aid the early diagnosis of chronic degenerative diseases in subclinical phase, as well as the development of strategies to prevent the processes of premature immune aging. Full article

Aucubin (AU) is one of the main components of the traditional Chinese medicine Eucommia ulmoides Oliv (EU). This study investigated the effects of AU on aging-related skeletal muscle atrophy in vitro and in vivo. The results of network pharmacology revealed the potential therapeutic effects of AU on muscle atrophy. In vitro, AU effectively attenuated D-gal-induced cellular damage, reduced the number of senescence-associated β-galactosidase (SA-β-Gal)-positive cells, down-regulated the expression levels of muscle atrophy-related proteins Atrogin-1 and MuRF1, and improved myotube differentiation, thereby mitigating myotube atrophy. Notably, AU was found to attenuate oxidative stress and apoptosis in skeletal muscle cells by reducing ROS production, regulating Cleaved caspase3 and BAX/Bcl-2 expression in apoptotic pathways, and enhancing Sirt1 and PGC-1α signaling pathways. In vivo studies demonstrated that AU treatment extended the average lifespan of Caenorhabditis elegans (C. elegans), increased locomotor activity, improved body wall muscle mitochondrial content, and alleviated oxidative damage in C. elegans. These findings suggested that AU can ameliorate aging-related muscle atrophy and show significant potential in preventing and treating muscle atrophy. Full article

Background: The efficacy of banaba leaf extract was tested against carboxymethyllysine (CML)-induced toxicity in embryos and adult zebrafish. Additionally, the individual and combined effects of banaba (BNB) and policosanol (PCO) were analyzed to alleviate dyslipidemia, hyperglycemia, and associated effects in streptozotocin (STZ)-induced hyperlipidemic diabetic zebrafish. Methodology: The high cholesterol diet (HCD, final 4%, w/w)-fed zebrafish were injected with STZ to develop diabetes and were subsequently fed with either HCD or HCD+BNB (final 0.1% w/w) or HCD+PCO (final 0.1% w/w) or HCD+BNB+PCO (each final 0.1%, w/w) each for 14 days. The zebrafish tail fin was amputated to assess tissue regeneration, while the organs and blood were collected for histological and biochemical analysis. Results: Severely compromised embryo survivability and developmental defects were noticed in the CML-injected group that significantly improved following BNB exposure. Similarly, CML-induced acute paralysis and mortality of adult zebrafish were effectively mitigated by the treatment with BNB. In the hyperlipidemic diabetic zebrafish, both BNB and PCO supplementation displayed the hypoglycemic effect; however, a remarkable reduction (p < 0.05) in blood glucose levels was observed in the BNB+PCO group, around 14% and 16% less than the BNB group and PCO group, respectively. Likewise, higher tail fin regeneration was noticed in response to BNB+PCO supplementation. Both BNB and PCO have a substantial counter-effect against HCD+STZ-induced dyslipidemia. However, the combined supplementation (BNB+PCO) displayed a significantly better effect than that of BNB and PCO alone to alleviate total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C). The most impressive impact of BNB+PCO was noticed in the elevation of high-density lipoprotein cholesterol (HDL-C), which was ~1.5 times higher than the HDL-C level in response to BNB and PCO. Also, BNB+PCO effectively reduced the malondialdehyde (MDA) and elevated the plasma sulfhydryl content, paraoxonase (PON), and ferric ion reduction (FRA) activity. Histological analyses revealed a significant effect of BNB+PCO in preventing inflammatory infiltration, fatty liver changes, and interleukin-6 production. Similarly, a notably better effect of BNB+PCO compared to their individual effect was noticed in preventing kidney damage and mitigation of ROS generation, apoptosis, and cellular senescence. Conclusions: The finding establishes the substantial effect of BNB and PCO in countering hyperglycemia, dyslipidemia, and associated disorders, which synergistically improved following the combined supplementation with BNB+PCO. Full article

The mammary gland undergoes significant changes throughout a woman’s life; from embryonic development to transformations after breastfeeding and during aging. These processes, while essential for normal breast physiology, can increase breast cancer risk when disrupted. This review explores three critical stages: embryonic development; postlactational involution; and age-related lobular involution (ARLI). We highlight key signaling pathways—Wnt, FGF, SHH, Notch, EGFR, and BMP—that guide embryonic development and discuss how their dysregulation can contribute to abnormal growth. For postlactational involution, we examine the two-phase process of cell death and tissue remodeling, showing how disruptions during this period, particularly postpartum, may foster a tumor-promoting environment. We also delve into ARLI and the role of cellular senescence in the aging mammary gland, focusing on the senescence-associated secretory phenotype (SASP) and its impact on inflammation and tissue remodeling. Understanding these processes provides new opportunities for breast cancer prevention and treatment strategies Full article

As a polyphenolic plant flavone, luteolin (Lut) is widely found in many medicinal plants, flowers, and vegetables. Although Lut has been shown to have the effect of preventing and treating skin photoaging, its role in preventing photoaging specifically induced by ultraviolet A (UVA) radiation remains underreported. In vivo, BALB/c mice were used as models for skin photoaging models and treated with Lut. Additionally, NIH-3T3 fibroblasts were utilized in vitro to further investigate whether Lut exerts its anti-photoaging effects by enhancing fibroblast vitality and function. Several biochemical assays (CCK-8, catalase, superoxide dismutase, malondialdehyde, dichloro-dihydro-fluorescein diacetate, quantitative real-time-PCR, gene expression patterns) and histochemical (histological staining, immunofluorescent staining, SA-β-Gal experiments, western blotting analysis) were conducted. The findings demonstrate that the Lut pretreatment could enhance the vitality and function of fibroblasts in both in vitro and in vivo experiments and inhibit UVA-induced collagen degradation, thereby improving the skin’s resistance to photoaging. We confirmed that the Lut pretreatment inhibited the expression of UVA-induced senescent factors P21, P16, and pro-inflammatory senescence-associated secretory phenotype (SASP) factors. Additionally, Lut exhibited potent antioxidant effects during UVA exposure. Bioinformatics and network pharmacology analyses revealed that Lut’s anti-photoaging effects may be mediated through the regulation of oxidative stress-related pathways and anti-aging genes. Upon utilizing inhibitors and agonists of oxidative stress, we further confirmed that Lut prevents UVA-induced fibroblast senescence by suppressing oxidative stress, and ultimately protects the skin from photoaging damage. These findings indicate that lutein mitigates photoaging caused by UVA-induced fibroblast senescence through the modulation of oxidative stress pathways. Full article

Centella asiatica, a traditional medicinal plant, possesses potent antioxidant activity and may therefore prevent cellular aging and exert antiapoptotic effects. However, these effects remain to be fully elucidated. This study aimed to investigate the protective effects of C. asiatica extract against cellular senescence and apoptosis caused by hydrogen peroxide (H₂O₂)-induced oxidative stress in human epidermal keratinocytes (HaCaT cells). To evaluate the effects of H₂O₂ and C. asiatica on HaCaT cells, we measured cell viability as a marker of cell death; reactive oxygen species (ROS), radical scavenging, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities as markers of oxidative stress; senescence-associated β-galactosidase (SA-β-gal) activity as a marker of cellular senescence; and caspase-3/9 activities and apoptotic cells as markers of apoptosis. H₂O₂ induced cell death (decreased cell viability), oxidative stress (increased ROS activity, decreased radical scavenging, SOD, GPx, and catalase activities), cellular senescence (increased SA-β-gal activity), and apoptosis (increased early/late apoptotic cells and increased caspase-3/9 activities). C. asiatica significantly decreased all markers of H₂O₂-induced cell death, oxidative stress, cellular senescence, and apoptosis, suggesting its ability to prevent cellular senescence and apoptosis through its antioxidant activity. This mechanism of action may contribute to the prevention and improvement of skin aging. Full article

Bone marrow mesenchymal stromal cells (BM-MSCs) are multipotent cells present in bone marrow; they play a crucial role in the process of bone formation. Cellular senescence is defined as a stable state of cell cycle arrest that impairs the functioning of cells. Research has shown that aging triggers a state of senescence in BM-MSCs, leading to a reduced capacity for osteogenic differentiation and the accumulation of senescent cells, which can accelerate the onset of various diseases. Therefore, it is essential to explore mechanisms and strategies for the rejuvenation of senescent BM-MSCs. Senile osteoporosis (SOP) is a metabolic bone disease characterized by reduced bone formation. The senescence of BM-MSCs is considered one of the most important factors in the occurrence and development of SOP. Therefore, the rejuvenation of BM-MSCs for the treatment of SOP represents a promising strategy. This work provides a summary of the functional alterations observed in senescent BM-MSCs and a systematic review of the mechanisms that facilitate the rejuvenation of senescent BM-MSCs. Additionally, we analyze the progress in and the limitations associated with the application of rejuvenated senescent BM-MSCs to treat SOP, with the aim of providing new insights for the prevention and treatment of SOP. Full article

Background: Ionizing radiation (IR) is a well-known inducer of cellular senescence and the senescence-associated secretory phenotype (SASP). SASP factors play dual roles in cancer, either promoting or inhibiting its development. This study investigates IR-induced SASP factors specifically secreted by renal cortical epithelial (RCE) cells and their role in promoting renal cell carcinoma (RCC) progression. Methods: Proteomic data from the SASP Atlas were analyzed to identify IR-induced factors unique to RCE cells, with subsequent evaluations performed at both the gene and protein levels. Thirty-seven proteins were identified as exclusively upregulated and secreted by senescent RCE cells. Gene expression analysis of these RCE-specific SASP factors was conducted using the Gene Expression database of Normal and Tumor tissues (GENT2) and The Cancer Genome Atlas (TCGA). To assess their prognostic relevance in RCC, the corresponding proteins were further analyzed using the Human Protein Atlas (HPA), emphasizing the relationship between SASP factor expression and RCC progression. Results: ALDH18A1 and ASPH emerged as key RCE-specific SASP factors with significant upregulation at both the gene and protein levels (Log2 ratio > 1.15, p < 0.05). These proteins are implicated in pro-cancer activities and are strongly associated with poor prognostic outcomes in RCC. Their critical roles in RCC progression underscore their potential as promising therapeutic targets for the prevention and treatment of the disease. Conclusions: This study provides novel insights into the role of IR-induced SASP in renal carcinogenesis, marking the first identification of ALDH18A1 and ASPH as specific secreted proteins associated with tumor progression in RCC. This study suggests that ALDH18A1 and ASPH hold promise as early biomarkers for RCC and as therapeutic targets for disease prevention and treatment. Full article

Periodontitis, a chronic multifactorial inflammatory condition of the periodontium, is originated by a dysbiotic oral microbiota and is negatively correlated with several systemic diseases. The low-chronic burden of gingival inflammation not only exacerbates periodontitis but also predisposes individuals to a spectrum of age-related conditions, including cardiovascular diseases, neurodegenerative disorders, and metabolic dysfunction, especially related to ageing. In this regard, over the local periodontal treatment, lifestyle modifications and adjunctive therapies may offer synergistic benefits in ameliorating both oral and systemic health in ageing populations. Elucidating the intricate connections between periodontitis and senescence is important for understanding oral health’s systemic implications for ageing and age-related diseases. Effective management strategies targeting the oral microbiota and senescent pathways may offer novel avenues for promoting healthy ageing and preventing age-related morbidities. This review will analyze the current literature about the intricate interplay between periodontitis, oral dysbiosis, and the processes of senescence, shedding light on their collective impact on the modulation and accelerated ageing and age-related diseases. Lastly, therapeutic strategies targeting periodontitis and oral dysbiosis to mitigate senescence and its associated morbidities will be discussed. Full article

The color and aroma of nectarines experience adverse effects from cutting, resulting in the fast senescence of fruit tissue. Therefore, 1-methylcyclopropene (1-MCP) was used to treat postharvest nectarines before cutting, and its effect on the surface browning and aroma alteration were investigated. The results indicated that 1-MCP restrained the soluble quinone (SQC) accumulation in fresh-cut nectarines by regulating the peroxidase (POD) and polyphenol oxidase (PPO) activities and the metabolism of phenolic compounds. Compared with the control, 1-MCP pre-cutting treatment maintained the ultrastructural integrity of the cell wall in fresh-cut nectarines, which also showed reduced malondialdehyde (MDA) content and reactive oxygen species (ROS) and enhanced the 1,1-Diphenyl-2-Picrylhydrazyl (DPPH) radical scavenging activities. Electronic nose and GC-MS analysis revealed that the aroma profiles presented significant differences in the control and 1-MCP treatment during the storage at 0 °C for 10 days. The browning value of the 1-MCP pre-cutting treatment was 29.95% lower than the control, which prevented the loss of aroma on day 10. The fresh-cut nectarines could still maintain the characteristic flavor, while the flesh maintains its firmness. The 1-MCP pre-cutting treatment improves the sensory and aroma characteristics of fresh-cut fruits, which is beneficial to the preservation of fresh-cut fruits, improves transportation efficiency, and then improves the overall quality and market attractiveness of the fruit. Full article

One class of cosmetic compounds that have raised interest of many experts is peptides. The search for ingredients with good biocompatibility and bioactivity has led to the use of peptides in cosmetic products. Peptides are novel active ingredients that improve collagen synthesis, enhance skin cell proliferation, or decrease inflammation. Based on their mechanism of action, they can be classified into signal peptides, carrier peptides, neurotransmitter inhibitor peptides, and enzyme inhibitor peptides. This review focuses on the main types of peptides and their application in the cosmetic field, underlining their main limitations. One of the most significant drawbacks of cosmetic peptides is their poor permeability through membranes, which limits their delivery and effectiveness. As a result, this review follows the methods used for improving permeability through the stratum corneum. Increasing peptide bioavailability and stability for enhanced delivery to the desired site of action and visible effects have become central points for the latest research due to their promising features. For this purpose, several methods have been identified and described. Physical techniques include thermal ablation (radiofrequency and laser), electrical methods (electroporation, iontophoresis), mechanical approach (microneedles), and ultrasounds. As an alternative, innovative formulations have been developed in nano-systems such as liposomes, niosomes, ethosomes, nanoemulsions, and other nanomaterials to reduce skin irritation and improve product effectiveness. The purpose of this review is to provide the latest information regarding these noteworthy molecules and the reasoning behind their use in cosmetic formulations. Full article