Onset Of Senescence Research Articles

Counteracting diabetes-induced adipose tissue derived-stromal cell senescence

Adipose tissue stromal cells (ADSCs) are prone to functional decline and senescence during metabolic disturbances. In diabetes mellitus (DM), the pathogenic microenvironment induces oxidative stress causing ADSCs to senesce. The senescence associated secretory phenotype (SASP) in turn drives disease progression. The pathogenesis of DM is thus both a cause and consequence of senescence. Therapeutically preventing the onset of senescence in ADSCs may play a significant role in preventing disease progression and directly impact the onset of comorbidities. The purpose of this study was to establish an in vitro model that mimic the DM micro-environment to use as a screening tool to assess the therapeutic efficacy of preventative and restorative agents. Exposing ADSCs (<passage 10) to a combination of high glucose, advanced glycation end products (AGE-BSA) and TNFα in culture for a period of 3 days induced senescence in 70 ± 4 % of cells (β-galactosidase assay). This coincided with increased ROS production, DNA damage (yH2Ax foci) and excessive release of SASP factors (IFNγ, TNFα, IL1β, IL8, IL6). Pretreatment of ADSCs as well as early intervention using either Metformin (50 μg/mL) or ascorbic acid 2 phosphate (AAP 0.6 mM) could prevent the onset of premature senescence. The expression of genes related to cell cycle (p21cip1, p16INK4A), apoptosis (p53), inflammation (TNFα, IL6, PTX3, IL10) and adipogenesis (PPARγ, UCP3) was assessed, with AAP pretreatment significantly reducing PTX3 expression. Although this study only investigated the early stages following senescence induction (3 days), subsequent studies could employ this model for longer duration and gain insight into premature senescence and the functional decline of ADSCs within the diabetic context, whilst limiting the use of animals.

Metabolome profile variation in Azolla filiculoides exposed to Bisphenol A assists in the identification of stress-responsive metabolites

This study attempted to explore the metabolome profile of Azolla filiculoides subjected to two different concentrations of BPA (1 and 30 mg L−1) in congruence with two different durations (3 and 9 days) of treatment. Bisphenol A (BPA) is a ubiquitously occurring environmental pollutant that imparts acute toxicity in aquatic plants. Therefore, studying the variations in the fern metabolome profile and identifying stress-responsive metabolites can help develop criteria for assessing the aquatic ecosystem. In recent times, metabolomics has drawn attention for its ability to detect biochemical processes and help link plant responses with environmental stresses. However, the studies concerning the metabolome profile of A. filiculoides exposed to environmental contaminants are limited. In the present study, the untargeted metabolomics study allowed the detection of a large array of metabolites, with 767 shared metabolites representing 41 crucial pathways. Exposure to 30 mg L−1 BPA seemingly disrupted the primary metabolism of the fern and induced a shift toward defense-related pathways. Additionally, BPA stress triggered the expression of metabolites like 3,4-dihydroxyphenylglycol, perillic acid, and perillaldehyde in BPA_L3 (1 mg L−1 for 3 days) and BPA_L9 (1 mg L−1 for 9 days) samples indicating protective mechanism of the plants. Conversely, the BPA_H3 (30 mg L−1 for 3 days) and BPA_H9 (30 mg L−1 for 9 days) samples expressed a distinct set of markers like luteolin, 3-hydroxyanthranilic acid, cinnamaldehyde, and l-DOPA indicating the onset of senescence and apoptosis related pathways can help in the health assessment of freshwater ecosystems and also appraisal of ecotoxicological risks imposed by BPA.

Hematopoietic Stem Cells from Mice and Individuals with Sickle Cell Disease Display Premature Senescence and Loss of Function That Is Targetable By Senolytic Therapy

Sickle cell disease (SCD) is an inherited anemia caused by mutations in the β-globin gene, resulting in aberrant hemoglobin polymerization driving hemolysis, vasooclusion, and systemic inflammation. Allogeneic hematopoietic stem cell (HSC) transplantation is potentially curative, and novel autologous therapies involving gene-editing of mobilized HSCs are being developed. However, many SCD patients are unable to undergo autologous gene-editing due to failure to mobilize sufficient numbers of HSCs. Further, the damaging effects of SCD on the HSC pool remain uncharacterized. Therefore, we interrogated young and aged cohorts of humanized SCD mice and non-SCD controls for HSC frequency and function. Immunophenotypic HSC frequency was mildly elevated (1.3-fold, p=0.00316) in 2-month-old SCD mice, relative to controls (n=5-6/group). In contrast, HSC numbers were halved in 6 and 12-month-old SCD mice (n=8-10/group, p=0.00358 and p=0.0148, respectively). Competitive transplantation of whole bone marrow (WBM) from 2 and 6-month-old SCD mice displayed a profound loss of peripheral blood repopulation, relative to age-matched control mice. Quantitative limiting dilution transplantation of WBM from 2 and 6-month-old SCD mice revealed a 4 and 6-fold loss of functional HSCs, relative to control mice. Thus, despite elevated numbers of phenotypic HSCs in young SCD mice, the HSC pool is depleted of functional repopulating cells during SCD. To understand the loss of functional HSCs, we performed bulk RNA-sequencing of purified HSCs from 6-month-old SCD mice. We observed downregulation of 37 genes encoding ribosomal and histone proteins, suggesting impaired histone/ribosome biogenesis, a phenotype associated with senescence. Consistently, pathway enrichment analysis also revealed perturbed p53 activity and a high degree of association with published molecular signatures of senescence. To explore this further, HSCs isolated from 6-month-old SCD mice or age-matched controls were interrogated for senescence associated β-galactosidase (SA-β-gal) activity. On average 19.5% of SCD HSCs were SA-β-gal+ versus only 7.06% of HSCs isolated from controls (n=10-11/group, p=0.004). HSCs isolated from SCD mice also displayed elevated ROS, DNA damage, and expression of molecular markers of senescence (e.g. p21, BCLXL). Importantly, 23.14 ± 5.61% of Lin-CD34+CD38- bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) isolated from pediatric individuals with SCD were SA-β-gal+. In contrast, only 4.97 ± 2.97% of HSPCs were SA-β-gal+ in age-matched, non-SCD control individuals (n=8 control and n=5 SCD individuals, p=&amp;lt;0.0001). Further, 47.46 ± 17.49% of Lin-CD34+CD38-CD90+CD45RA- BM cells, which are highly enriched for human HSCs, were SA-β-gal+ in young individuals with SCD, relative to only 4.41 ± 2.37% in the BM of age-matched control individuals (n=4 control and n=5 SCD individuals, p=0.0019). We also detected elevated expression of p16, p21, and BCL2 in BM HSPCs isolated from pediatric individuals with SCD, relative to controls (n=6 control and n=9 SCD individuals). In total, these data reveal that SCD pathophysiology aberrantly invokes senescence programs and damages HSC function in mice and humans. Clearance of senescent HSCs from mouse BM has previously been shown to restore aging-related HSC dysfunction. We therefore tested if clearance of senescent HSCs from the BM could restore function to the SCD HSC pool. 2-month-old SCD and control mice were treated with two weekly cycles of 75 mg/kg/day of the senolytic, ABT-263, via oral gavage. 14 days after treatment, WBM was isolated and tested for HSC function and frequency. Senolytic therapy significantly increased HSC numbers in SCD mice BM, relative to vehicle-treated controls (n=5/group). Importantly, the in vivo hematopoietic repopulating activity of WBM from ABT-263-treated SCD mice was comparable to non-SCD controls, revealing a correction of our previously observed severe transplantation defect (n=12/group). In sum, these data reveal premature onset of senescence as a previously unappreciated phenotype of the HSC pool during SCD. This work provides the first proof-of-principle that treatment of individuals with SCD using senolytics may restore function to the HSC pool, and ongoing preclinical work aims to test if senolytic therapy enhances the yield and function of SCD HSCs mobilized for autologous therapy.

Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype.

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence-associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation-related diseases. Altered BCAA metabolism driving the SASP is mediated by robust activation of the BCAA transporters Solute Carrier Family 6 Members 14 and 15 as well as downregulation of the catabolic enzyme BCAA transaminase 1 during onset of cellular senescence, leading to highly elevated intracellular BCAA levels in senescent cells. This, in turn, activates the mammalian target of rapamycin complex 1 (mTORC1) to establish the full SASP program. Transgenic Drosophila models further indicate that orthologous BCAA regulators are involved in the induction of cellular senescence and age-related phenotypes in flies, suggesting evolutionary conservation of this metabolic pathway during aging. Finally, experimentally blocking BCAA accumulation attenuates the inflammatory response in a mouse senescence model, highlighting the therapeutic potential of modulating BCAA metabolism for the treatment of age-related and inflammatory diseases.

The effect of antibody-mediated PCSK9 inhibitor on bare-metal stent implantation outcome

Abstract Introduction Percutaneous coronary intervention (PCI) is the gold standard for the management of acute coronary syndrome, and has been benefited from advances in pharmacotherapy and device innovation. Nevertheless, in-stent restenosis and stent thrombosis remain serious complications following PCI procedure with stent implantation. Proprotein convertase subtilisin kexin type 9 (PCSK9) is an enzyme known for its role in plasma cholesterol homeostasis. Efficiently reducing plasma cholesterol, PCSK9 inhibition recently became a pivotal treatment strategy for hypercholesterolemia. However, the effect of PCSK9 inhibition on stent implantation outcomes remains uninvestigated. Methods Carotid artery bare-metal stent (BMS) implantation was performed on C57Bl/6 mice, which then a parallel assessment of various inflammatory mediators was performed. To inhibit PCSK9, alirocumab was administered weekly to antiplatelet-treated mice started before stent implantation. Six weeks after the stent implantation procedure, animals were harvested and histomorphometric analysis was performed on stented arteries. In vitro cell migration and cellular senescence were also assessed on alirocumab-treated primary human aortic endothelial (EC) and vascular smooth muscle cells (VSMC). Results Compared to sham intervention, stent implantation was associated with increased expression of several inflammatory mediators, including PCSK9. Interestingly, the increase in PCSK9 level was confirmed in the stented vascular tissue, but not in plasma (Fig 1A). Following alirocumab treatment, PCSK9 inhibition results in an increased intimal hyperplasia in the stented vascular segment of alirocumab-treated animals compared to controls (Fig 1B). In vitro, alirocumab promoted migration and inhibited the onset of senescence in primary human VSMC, while blunted the migration and increased the senescence of EC. Conclusion The results of this study demonstrated that antibody-based PCSK9 inhibition worsen bare-metal stent implantation outcome in mice. This observed effect is mediated, in part, by the differential effect on VSMC and EC senescence, thus promoting in-stent intimal hyperplasia while blunting vascular healing. The herein-reported data warrant additional investigations concerning the use of PCSK9 inhibitors in patients undergoing PCI with stent implantation.

COG-imposed Golgi functional integrity determines the onset of dark-induced senescence.

Plant survival depends on dynamic stress-response pathways in changing environments. To uncover pathway components, we screened an ethyl methanesulfonate-mutagenized transgenic line containing a stress-inducible luciferase construct and isolated a constitutive expression mutant. The mutant is the result of an amino acid substitution in the seventh subunit of the hetero-octameric conserved oligomeric Golgi (COG) complex of Arabidopsis thaliana. Complementation studies verified the Golgi localization of cog7, and stress tests established accelerated dark-induced carbon deprivation/senescence of the mutant compared with wild-type plants. Multiomics and biochemical analyses revealed accelerated induction of protein ubiquitination and autophagy, and a counterintuitive increased protein N-glycosylation in senescencing cog7 relative to wild-type. A revertant screen using the overexpressor (FOX)-hunting system established partial, but notable rescue of cog7 phenotypes by COG5 overexpression, and conversely premature senescence in reduced COG5 expressing lines. These findings identify COG-imposed Golgi functional integrity as a main player in ensuring cellular survival under energy-limiting conditions.

Deep phosphorus fertilizer placement increases maize productivity by improving root-shoot coordination and photosynthetic performance

It’s well known that the development and distribution of roots could be regulated to obtain deep soil resource and enhance the grain yield by increasing the depth of fertilization, but little is known about whether increasing P fertilization depth can optimize the root distribution to delay leaf senescence, enhance photosynthetic performance and root-shoot coordination or not. We conducted a field experiment that tested the following four placement depths of P fertilization: 5 cm (P5), 10 cm (P10), 15 cm (P15), and 20 cm (P20). The experiment was designed to explore the regulatory effects of the P fertilization depth on the root growth and distribution, the photosynthetic performance, the root-shoot coordination, the yield formation, the N and P fertilizer utilization of maize plants. We found that deep P placement did indeed alter the root parameters. In the 20–60 cm soil layer, both the root dry weight and length of P15 treatment were on average 23.2% higher than those of P5 treatment. The specific root length and specific root surface area of P15 treatment were 4.5% and 5.6% higher than those of P5 treatment. In addition, the P15 treatment achieved a significantly improved photosynthetic performance over the P5 treatment: The leaf area index at the R6 stage was 10.2% higher, the leaf senescence index from the R2 to the R6 stages was 31.4% lower, the photosynthetic rate at the R3 stage was 25.9% higher. The P placement depth also optimized the root-shoot coordination: The ratios of root weight to shoot weight, root surface area to leaf area, and root length to leaf area of P15 treatment were 6.7%, 13.8%, and 12.7% higher than those of P5 treatment, respectively. Finally, the root P and N uptake efficiency, the photosynthetic P-use efficiency, and the physiological P-use efficiency of P15 treatment were all significantly higher than those of P5 treatments. And together these responses had the effect of increasing the mature biomass by 12.5%, and the grain yield by 22.0%. In conclusion, increasing the P fertilization placement depth to 15 cm regulates the growth and development of the root system, which in turn improves the capability of plant to uptake and utilize N and P in the soil, delays the onset of leaf senescence, enhances its photosynthetic performance and biomass accumulation rate, and thus ultimately increases the yield.

Cellular Senescence Program is Sensitive to Physical Differences in Polymeric Tissue Scaffolds.

A typical cellular senescence program involves exposing cells to DNA-damaging agents such as ionization radiation or chemotherapeutic drugs, which cause multipronged changes, including increased cell size and volume, the onset of enhanced oxidative stress, and inflammation. In the present study, we examined if the senescence onset decision is sensitive to the design, porosity, and architecture of the substrate. To address this, we generated a library of polymeric scaffolds widely used in tissue engineering of varied stiffness, architecture, and porosity. Using irradiated A549 lung cancer cells, we examined the differences between cellular responses in these 3D scaffold systems and observed that senescence onset is equally diminished. When compared to the two-dimensional (2D) culture formats, there were profound changes in cell size and senescence induction in three-dimensional (3D) scaffolds. We further establish that these observed differences in the senescence state can be attributed to the altered cell spreading and cellular interactions on these substrates. This study elucidates the role of scaffold architecture in the cellular senescence program.

TERRA R-loops connect and protect sister telomeres in mitosis

Resolution of cohesion between sister telomeres in human cells depends on TRF1-mediated recruitment of the polyADP-ribosyltransferase tankyrase to telomeres. In human aged cells, due to insufficient recruitment of TRF1/tankyrase to shortened telomeres, sisters remain cohered in mitosis. This persistent cohesion plays a protective role, but the mechanism by which sisters remain cohered is not well understood. Here we show that telomere repeat-containing RNA (TERRA) holds sister telomeres together through RNA-DNA hybrid (R-loop) structures. We show that a tankyrase-interacting partner, the RNA-binding protein C19orf43, is required for repression of TERRA R-loops. Persistent telomere cohesion in C19orf43-depleted cells is counteracted by RNaseH1, confirming that RNA-DNA hybrids hold sisters together. Consistent with a protective role for persistent telomere cohesion, depletion of C19orf43 in aged cells reduces DNA damage and delays replicative senescence. We propose that the inherent inability of shortened telomeres to recruit R-loop-repressing machinery permits a controlled onset of senescence.

Senescence-regulatory factors as novel circulating biomarkers and therapeutic targets in regenerative medicine for osteoarthritis

Recent discoveries reveal that the chronic presence of senescent cells in osteoarticular tissues provides a focal point of disease development for osteoarthritis (OA). Nevertheless, senescence-regulatory factors associated with OA still need to be identified. Furthermore, few diagnostic- and prognostic-validated biochemical markers (biomarkers) are currently used in clinics to evaluate OA patients. In the future, alongside imaging and clinical examination, detecting senescence-regulatory biomarkers in patient fluids could become a prospective method for disease: diagnosis, monitoring, progression and prognosis following treatment. This review summarizes a group of circulating OA biomarkers recently linked to senescence onset. Remarkably, these factors identified in proteomics, metabolomic and microRNA studies could also have deleterious or protective roles in osteoarticular tissue homeostasis. In addition, we discuss their potentially innovative modulation in combination with senotherapeutic approaches, for long-lasting OA treatment.

Ginsenoside F1-Mediated Telomere Preservation Delays Cellular Senescence.

Telomeres play pivotal roles in processes closely related to somatic senescence and aging, making them a compelling target for interventions aimed at combating aging and age-related pathologies. Ginsenoside, a natural compound, has emerged as a potential remedy for promoting healthy aging, yet how it protects telomeres remains incompletely understood. Here, we show that treatment of F1 can effectively restore the level of TRF2, thereby preserving telomere integrity. This restoration leads to inhibition of the DNA damage response and improvements in mitochondrial function and, ultimately, delays in cellular senescence. Conversely, depletion of TRF2 causes mitochondrial dysfunction, accompanied by increased oxidative stress, autophagy inhibition, insufficient energy metabolism, and the onset of cellular senescence. These observations underscore the critical role of TRF2 in maintaining telomere integrity and direct association with the initiation of cellular senescence. We conduct a further analysis, suggesting F1 could bind in proximity to the TRF2 heterodimer interface, potentially enhancing dimerization stability. These findings suggest that F1 may be a promising natural remedy for anti-aging, and restoring TRF2 could potentially prevent telomere-dependent diseases commonly associated with the aging process.

The multistep path to replicative senescence onset: zooming on triggering and inhibitory events at telomeric DNA.

Replicative senescence is an essential cellular process playing important physiological functions, but it is better known for its implications in aging, cancer, and other pathologies. One of the main triggers of replicative senescence is telomere shortening and/or its dysfunction and, therefore, a deep understanding of the molecular determinants is crucial. However, replicative senescence is a heterogeneous and hard to study process, especially in mammalian cells, and some important questions still need an answer. These questions concern i) the exact molecular causes triggering replicative senescence, ii) the role of DNA repair mechanisms and iii) the importance of R-loops at telomeres in regulating senescence onset, and iv) the mechanisms underlying the bypass of replicative senescence. In this review, we will report and discuss recent findings about these mechanisms both in mammalian cells and in the model organism Saccharomyces cerevisiae.

Age and sex-specific foraging movements and energetics in an endangered monomorphic seabird

Senescence is the irreversible decline in physiological functioning and survival with age. While this phenomenon has been studied in a range of different taxa, including seabirds, it has seldom been assessed for both sexes of monomorphic species, and in conservation contexts. Here, we studied the effect of age and sex on the foraging trip characteristics and energetics of the monomorphic Cape gannet (Morus capensis). Between 2017 and 2020, we used GPS recorders and miniaturised three-dimensional accelerometers to obtain data on the foraging trip characteristics and energy expenditure of 39 Cape gannets rearing chicks on Malgas Island, South Africa. This sample included 11 females and 28 males between the ages of 4 and 23 years. No difference in foraging trip characteristics was apparent between sexes or individuals of different ages. The energy expenditure of aging females (> 17 years) was higher than that of aging males. Aging females spent both more energy flying and less energy resting than males, despite similar foraging trip durations and distances. Males spent more energy diving and taking off from the water than females. The age-related sexual differences in energy expenditure presented in our study might reflect niche and/or risk partitioning strategies to ensure adequate provisioning to the chick, or a possible earlier onset of senescence in females relative to males. The higher energy expenditure of aging females, which presumably requires a concomitantly higher energy intake, likely reduces their resilience to environmental change.

Antibody-mediated PCSK9 neutralization worsens outcome after bare-metal stent implantation in mice

AimsDespite advances in pharmacotherapy and device innovation, in-stent restenosis (ISR) and stent thrombosis (ST) remain serious complications following percutaneous coronary intervention (PCI) procedure with stent implantation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme involved in plasma cholesterol homeostasis and recently emerged as a therapeutic target for hypercholesterolemia. Antibody-based PCSK9 inhibition is increasingly used in different subsets of patients, including those undergoing PCI. However, whether PCSK9 inhibition affects outcome after stent implantation remains unknown. Methods and results12 to 14 weeks old C57Bl/6 mice underwent carotid artery bare-metal stent implantation. Compared to sham intervention, stent implantation was associated with increased expression of several inflammatory mediators, including PCSK9. The increase in PCSK9 protein expression was confirmed in the stented vascular tissue, but not in plasma. To inhibit PCSK9, alirocumab was administered weekly to mice before stent implantation. After 6 weeks, histological examination revealed increased intimal hyperplasia in the stented segment of alirocumab-treated animals compared to controls. In vitro, alirocumab promoted migration and inhibited the onset of senescence in primary human vascular smooth muscle cells (VSMC). Conversely, it blunted the migration and increased the senescence of endothelial cells (EC). ConclusionAntibody-based PCSK9 inhibition promotes in-stent intimal hyperplasia and blunts vascular healing by increasing VSMC migration, while reducing that of EC. This effect is likely mediated, at least in part, by a differential effect on VSMC and EC senescence. The herein-reported data warrant additional investigations concerning the use of PCSK9 inhibitors in patients undergoing PCI with stent implantation.

Upstream migrant sea lamprey (Petromyzon marinus) show signs of increasing oxidative stress but maintain aerobic capacity with age

Following the parasitic juvenile phase of their life cycle, sea lamprey (Petromyzon marinus) mature into a reproductive but rapidly aging and deteriorating adult, and typically die shortly after spawning in May or June. However, pre-spawning upstream migrant sea lamprey can be maintained for several months beyond their natural lifespan when held in cold water (∼4-8 °C) under laboratory conditions. We exploited this feature to investigate the interactions between senescence, oxidative stress, and metabolic function in this phylogenetically ancient fish. We investigated how life history traits and mitochondria condition, as indicated by markers of oxidative stress (catalase activity, lipid peroxidation) and aerobic capacity (citrate synthase activity), changed in adult sea lamprey from June to December after capture during their upstream spawning migration. Body mass but not liver mass declined with age, resulting in an increase in hepatosomatic index. Both effects were most pronounced in males, which also tended to have larger livers than females. Lamprey experienced greater oxidative stress with age, as reflected by increasing activity of the antioxidant enzyme catalase and increasing levels of lipid peroxidation in liver mitochondrial isolates over time. Surprisingly, the activity of citrate synthase also increased with age in both sexes. These observations implicate mitochondrial dysfunction and oxidative stress in the senescence of sea lamprey. Due to their unique evolutionary position and the technical advantage of easily delaying the onset of senescence in lampreys using cold water, these animals could represent an evolutionary unique and tractable model to investigate senescence in vertebrates.

Effect of high night temperature on leaf senescence, physiological activity, and growth in soybean

Physiological processes that cause a negative growth response to high night temperatures (HNTs) were investigated in soybean. An HNT (28​°C) was established in a phytotron during the first (HL) and second (LH) halves of the reproductive stage and the entire (HH) reproductive stage, along with a continuously low (LL) night temperature (22​°C). Plant biomass was lower in HH than that in LL, whereas the harvest index was relatively stable. N accumulation in the plants tended to decline with HNT. The leaf area and leaf N concentration tended to be lower in HL and HH than in LL, suggesting an earlier onset of leaf senescence under HNT in the early reproductive stage. The light-saturated leaf photosynthetic rate was lower in HH than in LL during the late reproductive stage, associated with a low stomatal conductance and leaf photosynthetic rate per intercellular CO2 concentration. A slower rise in the leaf photosynthetic rate in the morning occurred likely because of the HNT, coinciding with the low leaf water potential at predawn and low leaf photosynthetic rate to intercellular CO2 concentration ratio. A moderately increasing gradient of night temperature from 21.7 to 23.9​°C was created in a mini-field in another experiment using a temperature gradient chamber, and in this experiment, crop growth and N dynamics were similar to those obtained in the phytotron study. These results suggest that the biomass growth of soybean is affected by HNT, particularly during the early reproductive stage.

BRCA1 heterozygosity promotes DNA damage-induced senescence in a sex-specific manner following repeated mild traumatic brain injury.

Emerging evidence suggests cellular senescence, as a consequence of excess DNA damage and deficient repair, to be a driver of brain dysfunction following repeated mild traumatic brain injury (rmTBI). This study aimed to further investigate the role of deficient DNA repair, specifically BRCA1-related repair, on DNA damage-induced senescence. BRCA1, a repair protein involved in maintaining genomic integrity with multiple roles in the central nervous system, was previously reported to be significantly downregulated in post-mortem brains with a history of rmTBI. Here we examined the effects of impaired BRCA1-related repair on DNA damage-induced senescence and outcomes 1-week post-rmTBI using mice with a heterozygous knockout for BRCA1 in a sex-segregated manner. Altered BRCA1 repair with rmTBI resulted in altered anxiety-related behaviours in males and females using elevated zero maze and contextual fear conditioning. Evaluating molecular markers associated with DNA damage signalling and senescence-related pathways revealed sex-specific differences attributed to BRCA1, where females exhibited elevated DNA damage, impaired DNA damage signalling, and dampened senescence onset compared to males. Overall, the results from this study highlight sex-specific consequences of aberrant DNA repair on outcomes post-injury, and further support a need to develop sex-specific treatments following rmTBI.

Lessons in aging from Myc knockout mouse models.

Despite MYC being among the most intensively studied oncogenes, its role in normal development has not been determined as Myc-/- mice do not survival beyond mid-gestation. Myc ± mice live longer than their wild-type counterparts and are slower to accumulate many age-related phenotypes. However, Myc haplo-insufficiency likely conceals other important phenotypes as many high-affinity Myc targets genes continue to be regulated normally. By delaying Myc inactivation until after birth it has recently been possible to study the consequences of its near-complete total body loss and thus to infer its normal function. Against expectation, these "MycKO" mice lived significantly longer than control wild-type mice but manifested a marked premature aging phenotype. This seemingly paradoxical behavior was potentially explained by a >3-fold lower lifetime incidence of cancer, normally the most common cause of death in mice and often Myc-driven. Myc loss accelerated the accumulation of numerous "Aging Hallmarks", including the loss of mitochondrial and ribosomal structural and functional integrity, the generation of reactive oxygen species, the acquisition of genotoxic damage, the detrimental rewiring of metabolism and the onset of senescence. In both mice and humans, normal aging in many tissues was accompaniued by the downregulation of Myc and the loss of Myc target gene regulation. Unlike most mouse models of premature aging, which are based on monogenic disorders of DNA damage recognition and repair, the MycKO mouse model directly impacts most Aging Hallmarks and may therefore more faithfully replicate the normal aging process of both mice and humans. It further establishes that the strong association between aging and cancer can be genetically separated and is maintained by a single gene.

Modified atmosphere packaging delays postharvest leaf senescence of Chinese flowering cabbage via suppressing chloroplast dismantling and alleviating mitochondrial oxidative damage

Onset of leaf senescence comes with biomolecule degradation and cellular organelle degeneration. Here, we examined the efficacy of modified atmosphere packaging (MAP) on reactive oxygen species (ROS) metabolism and ultrastructural changes of chloroplasts and mitochondria in Chinese flowering cabbage leaves during storage at 20 ± 1 ℃. MAP delayed chloroplast dismantling along with lower chlorophyll reduction and Fv/Fm ratio. Furthermore, the integrity of mitochondrial ultrastructure was maintained by MAP treatment during leaf senescence. MAP treatment also lowered accumulation of ROS and maintained higher levels of key components and enzyme activity of ascorbate–glutathione cycle, as well as expression of BrAPX5, BrGR, BrDHAR1 and BrMDHAR2. Additionally, MAP-treated cabbage leaves showed higher activity of peroxidase, superoxide dismutase, catalase and encoding gene expressions. Collectively, above findings suggest that MAP treatment could suppress chloroplast dismantling and maintain ROS homeostasis to mitigate mitochondrial oxidative damage and sustain mitochondrial structure, thereby postponing senescence of Chinese flowering cabbage.

Developing an operational algorithm for near-real-time monitoring of crop progress at field scales by fusing harmonized Landsat and Sentinel-2 time series with geostationary satellite observations

Crop phenology has been widely detected from multiple historical satellite observations. Conversely, Near-Real-Time (NRT) monitoring of crop progress from timely available remote sensing data is barely investigated because of the lack of high-frequency cloud-free satellite observations and future potential crop development. To address the challenge, this study proposes a novel algorithm for operational NRT monitoring of crop progress at the field scale. This algorithm first fuses the high spatial resolution (30 m) Harmonized Landsat and Sentinel-2 (HLS) data and the high temporal frequent (10 min) Advanced Baseline Imager (ABI) observations to generate cloud-free time series of HLS-ABI EVI2 (two-band Enhanced Vegetation Index) with a Spatiotemporal Shape-Matching Model (SSMM). It then predicts future potential EVI2 values at a given pixel using a reference EVI2 time series obtained from the neighboring pixels in the preceding year. Integrating the currently available HLS-ABI observations and the predicted future EVI2 values to generate annual EVI2 time series, the algorithm finally detects six crop phenometrics including greenup onset, mid-greenup phase, maturity onset, senescence onset, mid-senescence phase, and dormancy onset. The NRT monitoring, which are separated as near-real-time prediction (phenological event detected after the occurrence), real-time prediction (phenological event detected around the occurrence), and short-term prediction (phenological event detected before the occurrence), are continuously updated and improved with new HLS and ABI observations at a weekly basis throughout the growing season. We evaluate the NRT monitoring against standard phenology products, PhenoCam observations, as well as the weekly Crop Progress Reports (CPRs) released from the National Agricultural Statistics Service (NASS) of the United States Department of Agriculture (USDA) in 2020 across Iowa. The evaluation demonstrates the robustness of the developed algorithm in NRT monitoring of crop phenology. Although the uncertainties are relatively large for short-term prediction compared with standard detections, the real-time prediction shows that the Mean Absolute Difference (MAD) is <10 days for greenup and dormancy onset, and ∼ 5 days in the other four phenometrics. Further, the real-time prediction aligns well with PhenoCam observations (R2 = 0.96, P < 0.001) with a MAD of 7.8 days. Moreover, the HLS-ABI real-time prediction of crop phenometrics is capable of tracking NASS crop progress closely with small time shifts (≤ 5 days) and significant correlations (R2 > 0.85, P < 0.001) for various phenological stages of corn and soybean. These results prove that the algorithm could be implemented for NRT monitoring of various crop phenometrics from field, state, to national scales.