Aging is associated with progressive testicular dysfunction, including disruption of the blood-testis barrier (BTB), loss of junctional proteins, impaired spermatogenesis, and reduced fertility. This study examined the therapeutic effects of Mucuna pruriens (M. pruriens), a leguminous plant with potent antioxidant and anti-inflammatory properties, on age-related degeneration of testicular junctional molecules in male Wistar albino rats. Adult (4-5months) and aged (20-22months) rats were divided into M. pruriens-treated and untreated groups, with 6 animals in each group. The treatment groups received a dose of M. pruriens seed extract (gavage) of 200mg/Kg body weight for an experimental period of 45d. Testicular tissues were analyzed via histology, Western blotting, and immunofluorescence to assess BTB protein expression, while epididymal sperm were evaluated for count, motility, viability, and membrane integrity. Results showed that aging causes a significant decrease in BTB proteins, including claudin-1, E-cadherin, N-cadherin, β-catenin, and zonula occludens-1 (ZO-1), along with disrupted seminiferous tubules, thinning of the epithelium, increased interstitial spaces, Sertoli cell vacuolization, and germ cell loss. However, M. pruriens-treated rats showed increased expression of the mentioned BTB proteins. In treated aged rats, the anti-inflammatory cytokine TGF-β emerged as a senescence marker, whereas IL-10 levels mirrored those of IL-6. Pro-inflammatory markers TNFα and IL-1β decreased in the M. pruriens-treated groups. At the same time, MIF, AR and ERα expression increased in the aged rats treated with M. pruriens, indicating recovery of the testicular microenvironment. Functionally, aged rats experienced notable reductions in sperm count, viability, motility, and membrane integrity. Conversely, M. pruriens-treated aged rats displayed a marked restoration of BTB protein levels and proper localization at Sertoli-Sertoli and Sertoli-germ cell junctions. Histological analysis showed improved seminiferous structures, fewer interstitial gaps, a thicker germinal epithelium, and increased spermatozoa. M. pruriens treatment significantly enhanced sperm parameters in aged rat testes. These findings demonstrate that M. pruriens supplementation can reduce age-related testicular degeneration by restoring junctional protein expression, maintaining BTB integrity, and supporting spermatogenesis.

Pharmacological modulation of ageing is viewed as a viable route to extending lifespan and healthspan, yet the efficacy of putative geroprotectors may depend strongly on physiological and environmental context. Lithium chloride (LiCl) has been reported to extend lifespan in several model organisms, but evidence remains inconsistent and the role of reproductive investment-an energetically costly and often lifespan-correlated process-has rarely been examined. We tested the effects of dietary LiCl on survival and reproductive performance in male Drosophila melanogaster, comparing unmated (UM) and frequently-mated (FM) males. Contrary to previous work, both a concentration previously reported as beneficial (25 mM), and a lower concentration (10 mM) reduced survival, with effects driven exclusively by UM males. FM males were comparatively protected, revealing a strong mating-dependent interaction. LiCl had no detectable effect on male late-life mating latency, sterility, or paternity share, but reduced some post-copulatory performance in FM males by increasing female remating, indicating that somatic and reproductive responses to LiCl can be decoupled. These results demonstrate that lithium's effects on survival are strongly dependent on reproductive environment, highlighting the importance of reproductive context when evaluating its impact on lifespan.

Fat plays a key role in maintaining energy balance and supporting various physiological processes. HuAge-related disorders in fat utilization are increasingly prevalent, contributing to impaired energy balance, heightened metabolic disease risk, and increased cardiovascular dysfunction. The mechanism of age-induced disorders of fat utilization remains unclear. This study aims to explore the key factor affecting fat digestion and absorption during aging. Mice of different ages were used to analyze the changes of physiological and metabolic parameters with aging, including metabolic rate, energy expenditure, lean mass and apparent digestibility. Results showed that respiratory energy metabolism declined and fat apparent digestibility decreased significantly by more than 4% with aging. Fat is initially hydrolyzed in the intestine through combined actions of digestive enzymes and bile acids. Thus, the pancreatic lipase activity and total bile acids content were measured. The results revealed no significant changes in these factors. Furthermore, factors affecting fat absorption including intestinal structure and transporters expression were assessed. It was found that the crypt depth and villi height did not change significantly with age. Notably, intestinal proteomics analysis indicated that the expression of fatty acid transporter protein 4 (FATP4) was reduced by more than 50% in aged mice. In conclusion, this study demonstrated that age-related decline in FATP4 expression is linked to impaired intestinal fat absorption. This association may underlie the decreased fat apparent digestibility and impaired fat utilization during aging. These findings reveal the intrinsic mechanisms of age-induced dysregulation of fat utilization and providing a theoretical basis for enhancing fat utilization in older adults.

Circulating tumor DNA (ctDNA), the tumor-originating fraction of cell-free DNA (cfDNA), is widely used as a biomarker for cancer detection and therapeutic monitoring; however, its direct biological impact on normal cells remains insufficiently understood. Since ctDNA contains tumor-derived molecular features, we hypothesized that it could serve as a signal that induces stress responses in healthy stromal cells. In this study, ctDNA and cfDNA were isolated from the conditioned media of B16-F10 melanoma and L929 fibroblast cultures, respectively, and applied to mouse embryonic fibroblasts (MEFs) at concentrations of 100 and 500ng/mL for 24h. Senescence was evaluated by SA-β-Gal staining alongside quantitative PCR analysis of senescence and SASP-associated genes, including p16, p21, p53, IL-6, and IL-1β. ctDNA treatment induced a pronounced, dose-dependent increase in senescence marker expression and SASP cytokine production, accompanied by elevated SA-β-Gal staining, whereas cfDNA treatment elicited no significant change compared to controls. These results indicate that ctDNA may act as a biologically active stimulus capable of eliciting senescence-like responses in normal fibroblasts, supporting the possibility that tumor-derived extracellular nucleic acids contribute to alterations in stromal behavior within the tumor microenvironment.

A newly identified specific category of non-coding RNA (ncRNA), circRNAs, is drawing interest for their role in controlling several biological processes including muscle regeneration, aging, and adaptation to physical activity. Unlike linear RNAs, circRNAs are very stable and can have long-lasting regulatory impact since they create a covalently closed loop structure. Emerging evidence indicates that circRNAs play a pivotal role in skeletal muscle biology by regulating myogenesis, satellite cell activation, protein synthesis, and cellular senescence-processes significantly influenced by aging. These molecules are crucial for muscle function and regeneration, acting as microRNA sponges, interacting with RNA-binding proteins, and modulating gene expression and translation. Exercise-especially resistance and endurance training-has been shown to change circRNA expression in skeletal muscle, therefore possibly reducing age-related muscle loss and improving regenerative capacity. Though encouraging, much of the circRNA in muscle biology research is still in its early stages, with few functional studies and varying outcomes across various species and exercise models. Moreover, the exact ways circRNAs affect muscular adaptation to exercise and stop aging-related degeneration are still not completely known. This review addresses the existing knowledge gaps regarding the potential therapeutic applications of circRNAs in combating muscle degeneration and sarcopenia, as well as their role in muscle health and aging.

Aging is marked by progressive dysfunction in cellular maintenance pathways, including mitochondrial impairment, reduced autophagic capacity, and accumulation of senescent cells, which contribute to chronic low-grade inflammation. The transmembrane protein CD47 best known for delivering a "don't eat me" signal through SIRPα is increasingly recognized as an important modulator of several aging-related processes. Its upregulation in aged or inflamed tissues can inhibit the clearance of damaged or senescent cells, reinforce inflammatory signaling through pathways such as NF-κB, and influence metabolic and autophagy-related regulation in a context-dependent manner. This review synthesizes current evidence identifying CD47 as an integrative node that intersects with multiple hallmarks of aging. We examine its roles across cardiovascular, neurodegenerative, and metabolic pathologies, and evaluate the emerging therapeutic landscape targeting the CD47-SIRPα axis. Although CD47 blockade has shown promise in enhancing immune clearance and improving tissue homeostasis, clinical translation remains challenged by on-target toxicities such as anemia and by age-dependent variability in immune responsiveness. Targeting CD47 therefore represents a mechanistically grounded but inherently complex strategy for mitigating age-related functional decline.

As a target organ in direct contact with external air, lung tissue is more susceptible to aging, and lung aging is closely related to the development of chronic lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis. Evolutionarily speaking, the Wnt signaling pathway is highly conserved and plays an important role in embryonic development, tissue homeostasis, as well as cell proliferation, differentiation, apoptosis, and migration of a variety of cells. Alterations in Wnt signaling pathway activity can accelerate the pathological process of chronic lung diseases. In recent years, a large number of studies have focused on the regulatory role of the Wnt signaling pathway in the lung aging process and aging-related chronic lung diseases. Therefore, this paper systematically reviews the relationship between the Wnt signaling pathway and lung aging and its role in aging-related chronic lung diseases.

Aging involves a progressive decline in physiological function, leading to organ damage and age-related chronic diseases. Natural products derived from traditional herbs represent a valuable resource for identifying anti-aging compounds and potential lead candidates. In this study, a screen of an herbal library using Caenorhabditis elegans (C. elegans) identified the 75% ethanol extract of Callicarpa nudiflora Hook (LWLY01) as a potent lifespan-extending agent. Further fractionation revealed that its ethyl acetate extract (LWLY03) exhibited significant anti-aging activity, albeit with complex composition. Through systematic isolation and identification, verbascoside was determined to be a key active constituent. Verbascoside extended the lifespan of C. elegans and improved healthspan parameters, including motility and resistance to osmotic and thermal stress. Mutant lifespan assays demonstrated that verbascoside acts through activation of the SKN-1 signaling pathway, thereby strengthening resistance to aging-associated oxidative stress. Additionally, verbascoside was found to regulate multiple aging-related processes, such as stress response, oxidative damage, and cellular homeostasis. These findings highlight verbascoside as a promising natural compound for mitigating aging phenotypes and preventing age-related diseases.

Amyloid-β (Aβ) plaques are one of the primary biomarkers of Alzheimer's Disease (AD). Other publications have reported various mechanisms regarding the clearance of Aβ, and recent studies have also investigated the relationship between daily rhythms of Aβ and AD. The intent of this study was to determine if the circadian rhythm of Aβ differed between a region that was more vulnerable to AD-related pathology (the olfactory bulbs; OB) compared to a region that is less vulnerable (the cerebellum; CER). We chose to utilize an APPxPS1 knock-in (KI) mouse strain as this strain expresses amyloid precursor protein (APP) and Aβ under control of its normal promoter as opposed to AD transgenic models that overexpress APP and, as a consequence, Aβ. Mice (N = 128, equally divided between male and female, wild type and KI) were acclimated to a 12:12 light cycle for two weeks, and tissue was collected over a 24-h period in constant darkness. Using a unique immunoassay designed to measure human or rodent Aβ side-by-side, we confirmed a robust circadian Aβ rhythm in the mouse brain and that the OB contains more overall Aβ accumulation than the CER. The circadian Aβ rhythm was not present in the OB of the KI as compared to the WT mice. In contrast, the Aβ rhythm in the CER did not differ between genotypes. These results suggest that the loss of Aβ rhythm in disease-affected brain regions may be associated with the development of AD pathology and could have important implications for therapy.

An accumulation of senescent cells within tissues is a hallmark of the aging process. Cellular senescence is associated with an increased level of cytosolic dsDNA which primarily originates from a leakage of mitochondrial DNA (mtDNA) and a loss of genomic DNA integrity. Cytosolic dsDNA is an important alarming factor for cytosolic dsDNA sensors which trigger the remodeling of the immune system through diverse signaling pathways. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) (cGAS-STING) signaling is a major defence mechanism induced by an accumulation of cytosolic dsDNA in senescent cells. The cGAS-STING pathway stimulates immune responses via the interferon regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB)-driven pathways. The activation of cGAS-STING signaling in senescent cells generates pleiotropic immune responses in a context-dependent manner. For instance, cGAS-STING signaling induces proinflammatory responses by enhancing the secretion of cytokines, chemokines, and colony-stimulating factors. The secretion of many chemokines and colony-stimulating factors can remodel hematopoiesis and enhance thymic involution with aging. Moreover, cGAS-STING signaling promotes proinflammatory responses by stimulating the NLRP3 inflammasomes. On the other hand, cGAS-STING signaling aids in the resolution of inflammation by recruiting immunosuppressive cells into tissues and suppressing the pathogenic activity of T helper 17 cells. In addition, an increased cGAS-STING signaling in senescent cells stimulates the expression of inhibitory immune checkpoint ligands, such as PD-L1, and thus prevents their elimination by immune cells. Recent studies have clearly revealed that cGAS-STING signaling not only induces cellular senescence but it can also promote the aging process.