Physiological Aging Research Articles

Storage Temperature Effect on Quality and Shelf-Life of Hericium erinaceus Mushroom

Hericium erinaceus, commonly known as Lion’s Mane mushroom, presents a challenge for maintaining quality and shelf-life during post-harvest storage. This study investigates the impact of different temperatures (5 °C, 13 °C, and 21 °C) during 14 days of storage, on the physicochemical, microbiological, and bioactive characteristics of H. erinaceus. Respiration was measured as an indicator of physiological aging, showing that higher temperatures increased CO2 production as well as O2 depletion. Physicochemical assessments, including moisture content, pH, titratable acidity, weight loss, browning index, and firmness, demonstrated that refrigeration at 5 °C best preserved the mushrooms’ quality. Storage at 5 °C effectively minimized microbial proliferation, maintaining acceptable levels until day 7 but showing increased contamination by day 14. However, higher temperatures promoted antioxidant activity and total phenolic content, likely due to moisture loss and oxidative stress. These findings highlight the critical role of low-temperature storage in preserving both the physicochemical integrity and functional bioactivity of H. erinaceus, and suggest further research into packaging solutions and preservation strategies to optimize the post-harvest handling of H. erinaceus.

Handgrip strength as a potential indicator of aging: insights from its association with aging-related laboratory parameters

IntroductionThe aging process is frequently associated with a decline in functional capacity, endurance, muscle quality, and overall quality of life. Examining aging-related biomarkers often requires significant time and financial resources, underscoring the need for a straightforward and practical indicator. This study aims to investigate the association between handgrip strength and aging-related laboratory parameters in the elderly population of Indonesia.MethodsA cross-sectional study was conducted involving 109 participants aged 60–82 years. Handgrip strength was measured using a Jamar hydraulic hand dynamometer and Jamar PLUS+ digital dynamometer. Aging-related laboratory biomarkers were defined as those indicating physiological aging processes.ResultsThe study revealed a significant association between handgrip strength and several aging-related laboratory parameters, including leukocyte count, absolute neutrophil count, absolute lymphocyte count, neutrophil/lymphocyte ratio, and erythrocyte sedimentation rate.DiscussionThese findings suggest that handgrip strength could serve as a cost-effective, non-invasive predictor of aging-related health status in older adults. Its practical utility highlights its potential for guiding health interventions targeting the elderly population.

A framework of biomarkers for skeletal muscle aging: a consensus statement by the Aging Biomarker Consortium

Abstract The skeletal muscle is an important organ for movement and metabolism in human body, and its physiological aging underlies the occurrence of muscle atrophy and sarcopenia. China has the largest aging population in the world and is facing a grand challenge with how to prevent and treat skeletal muscle aging-related diseases. To address this difficult problem, the Aging Biomarker Consortium (ABC) of China has reached an expert consensus on biomarkers of skeletal muscle aging by synthesizing literatures and insights from scientists and clinicians. This consensus attempts to provide a comprehensive assessment of biomarkers associated with skeletal muscle aging, and proposes a systematic framework to classify them into three dimensions: functional, structural, and humoral. Within each dimension, the experts recommend clinically relevant biomarkers for skeletal muscle aging. This consensus aims to lay the foundation for future research on skeletal muscle aging, facilitating precise prediction, diagnosis, and treatment of skeletal muscle aging and sarcopenia. It is anticipated to make significant contributions to healthy aging of skeletal muscle in the elderly population in China and around the world as well.

Association of Environmental Temperature and Relative Humidity with Ocular and Flank Temperatures in Dromedary Camels

Heat stress represents significant challenges for livestock, adversely affecting their production, reproduction, and overall welfare. This study aimed to explore the interrelationships between environmental and animal-related factors and the flank temperature (FT) and eye temperature (ET) recorded using IRT in dromedary camels. This study was conducted in the Cholistan Desert in 2023, and IRT images of the eyes and flanks were captured from 510 camels across 54 herds. During the image analyses, pictures taken from 499 camels were of good quality and included. The camels were of both sexes and of various ages (minimum 3 years, pubertal and adult stages), and they had diverse physiological statuses (breeding, immature, lactating, non-lactating, and pregnant). Before taking the IRT pictures, ambient temperature and humidity were registered using a weather station, and light intensity was recorded using a lux meter. The ET was associated only with physiological status (p < 0.05), with pregnant females showing the lowest values, while no effects of physiological status, sex, or age were found for FT. The environmental temperature showed a positive correlation with both ET (r = 0.7887) and FT (r = 0.6280), highlighting the sensitivity of camel thermoregulation to temperature fluctuations. As expected, a strong positive correlation between ET and FT (r = 0.6643) was found. Conversely, a significant negative correlation was observed between humidity and ET (−0.7444) and FT (−0.5519), indicating that higher humidity levels lead to decreased temperatures in both regions. Light intensity (lux) exhibited minimal influence on both temperatures, with correlations of 0.1019 for ET and 0.2650 for FT. This study contributes to the field of precision livestock farming by suggesting a possible application of IRT for detecting thermal stress in camels in pastoral settings.

Socio-hygienic portrait of patients with arterial hypertension in Kazakhstan in modern conditions

Introduction. The article notes that the greatest contribution to the structure of causes of death and disability associated with cardiovascular diseases identified as a result of the study falls on patients with arterial hypertension. Social and hygienic portrait of a patient with arterial hypertension. Age – most often occurs in people over 40 years of age, the most common age is 40-60 years, the highest incidence is observed in this age group. At this age, there is a physiological aging of the vessels and an increase in blood pressure. After over 60 years: the incidence increases and the detection of AG among older people increases significantly due to age-related changes in the circulatory system and the presence of concomitant diseases. Among men by gender, the incidence of hypertension is most often observed in men in young and middle age (up to 60 years). This is due to high levels of stress, alcohol consumption, smoking and a sedentary lifestyle. And among women, the difference in morbidity between the ages of 60 and older decreases, and women begin to suffer from hypertension as much as men. This can lead to an increase in blood pressure due to changes in the hormonal background, especially after menopause.In terms of social characteristics, a low level of education may predispose to not being aware of the risks associated with arterial hypertension, as well as a healthy lifestyle.Aim. To characterize the modern socio-hygienic characteristics of the personality of patients with arterial hypertension.Materials and methods. A comprehensive medical and sociological study was conducted from 2020 to 2023 on the basis of Karaganda city polyclinic No. 3. The research program is implemented in accordance with the goals and objectives of the doctoral work, and the research practice is based on specific criteria. Results and discussion. Among the respondents, the largest number were patients aged 54-62 years (N = 241; 58.1%). In addition, the proportion of representatives of this age group among the women surveyed exceeded the statistically significant (p<0.05) similar indicator among men (67.4 and 45.3%, respectively).Conclusion. The results of our study confirm that, like other authors who conducted similar studies when planning and implementing preventive measures related to hypertension, men of working age should be especially attentive as a category of people with more pronounced risk factors for hypertension and rarely spread to medical organizations.

Interplay of Neighborhood and Psychosocial Factors in Predicting Trajectories of Allostatic Load Among Latinx Adults in the United States

Research highlights the independent roles of neighborhood and psychosocial risk and protective factors for accelerated physiological aging. However, the combined role of neighborhood and psychosocial factors for allostatic load among Latinx adults in the U.S. remains unclear. Informed by the Health Disparities Framework, the study aims are to: (1) examine the direct associations between neighborhood (cohesion and disorder) and psychosocial (loneliness) factors, respectively, and allostatic load trajectories; and (2) determine whether family social support moderates the association between loneliness and allostatic load trajectories. Data for Latinx adults ages ≥50 ( n = 319) are from the Health and Retirement Study (waves 2006–2016). Linear mixed models estimated baseline and rate of change in allostatic load, adjusting for sociodemographics. Loneliness was positively associated with baseline allostatic load. This association persisted when we considered neighborhood factors. Family social support moderated the association between loneliness and allostatic load slope. As neighborhood features, loneliness, and physiological dysregulation are each associated with worse cognitive outcomes, findings underscore the protective role of family social support for physiological dysregulation, thereby promoting cognitive resilience.

Droplet-based high-throughput 3D genome structure mapping of single cells with simultaneous transcriptomics

Single-cell three-dimensional (3D) genome techniques have advanced our understanding of cell-type-specific chromatin structures in complex tissues, yet current methodologies are limited in cell throughput. Here we introduce a high-throughput single-cell Hi-C (dscHi-C) approach and its transcriptome co-assay (dscHi-C-multiome) using droplet microfluidics. Using dscHi-C, we investigate chromatin structural changes during mouse brain aging by profiling 32,777 single cells across three developmental stages (3 months, 12 months, and 23 months), yielding a median of 78,220 unique contacts. Our results show that genes with significant structural changes are enriched in pathways related to metabolic process and morphology change in neurons, and innate immune response in glial cells, highlighting the role of 3D genome organization in physiological brain aging. Furthermore, our multi-omics joint assay, dscHi-C-multiome, enables precise cell type identification in the adult mouse brain and uncovers the intricate relationship between genome architecture and gene expression. Collectively, we developed the sensitive, high-throughput dscHi-C and its multi-omics derivative, dscHi-C-multiome, demonstrating their potential for large-scale cell atlas studies in development and disease.

Assessment of cfDNA release dynamics during colorectal cancer surgery.

Approximately two-thirds of patients with colorectal cancer (CRC) undergo resection with curative intent; however, 30% to 50% of these patients experience recurrence. The concentration of cell-free DNA (cfDNA) before and after surgery may be related to the prognosis of patients with CRC, but there is limited information regarding cfDNA levels at the time of surgery. Here, we analyzed surgical cfDNA release using plasma samples from 30 colorectal cancer patients at three key points during surgery: preoperative (immediately before surgery), intraoperative (during surgery), and postoperative (at the end of surgery). Automated electrophoresis was used to analyze cfDNA concentrations and fragment sizes, which were then correlated with clinical variables. Our findings indicate a significant increase in cfDNA release during and after surgery (2.8- and 2.2-fold higher respectively, p < 0.01). Characteristic fragments of cfDNA (<400 bp) predominated at all surgical stages; however, the release of genomic material (>400 bp) was also observed. We found that cfDNA concentration increases during and after surgery in patients over 60 years old (2.9-fold higher intraoperatively than preoperatively and 2.3 folds higher postoperatively than preoperatively, p < 0.01); in patients with comorbidities (3.0-fold higher intraoperatively and 2.3-fold higher postoperatively, p < 0.01); and in patients with CEA levels >5 ng/mL (3.1-fold higher intraoperatively and 1.3-fold higher postoperatively, p < 0.01). Interestingly, cfDNA release during surgery is significantly higher in patients with adverse clinical characteristics. Patients bearing locally advanced tumors or metastasis had a 3.1-fold increase in cfDNA release intraoperatively and 2.4-fold increase postoperatively, p < 0.01. cfDNA concentration also increases intraoperatively in patients with a high score of tumor buds (2.6 folds higher, p < 0.02), patients with perineural invasion (3.4-fold higher, p < 0.02) and in patients with lymphovascular invasion (3.1-fold higher, p < 0.05). Furthermore, we observed that cfDNA concentration may rise in correlation with the duration of the surgery, highlighting its potential as a marker of surgical quality. Taken together, our results suggest that in addition to physiological age, comorbidities and unfavorable clinical traits, intense surgical manipulation from the tumor's extent, may result in greater tissue damage and elevated cfDNA release.

Neuroglial decline defines cognitive ageing

Neuroglia of the central nervous system, represented by astroglia, oligodendroglia and microglia, are fundamental for life-long support of homeostasis, plasticity and defence of the neural tissue. In particular neuroglial cells contribute to the cognitive reserve, which defines the neurological and cognitive outcome of both physiological and pathological ageing. Physiological ageing is accompanied with structural and functional decline of neuroglia. In particular, astrocytes undergo morphological atrophy and functional asthenia which compromises their vital functions such as glutamate clearance, K+ buffering and synaptic support. Old oligodendrocytes lose their myelination capacity, which results in the thinning of myelin sheath and atrophy of white matter. Finally, ageing is associated with accumulation of dystrophic microglia which limits neuroprotection. Age-dependent neuroglial decline impedes cognitive reserve, contributes to cognitive impairment, and increases vulnerability of the nervous system to neurodegeneration. Life style changes positively impact on neuroglial structure and function this improving cognitive longevity. Keywords: ageing; cognitive longevity; neuroglia, astroglia, oligodendroglia; oligodendroglial precursor cells; microglia

Human longevity and Alzheimer's disease variants act via microglia and oligodendrocyte gene networks.

Ageing underlies functional decline of the brain and is the primary risk factor for several neurodegenerative conditions, including Alzheimer's disease (AD). However, the molecular mechanisms that cause functional decline of the brain during ageing, and how these contribute to AD pathogenesis, are not well understood. The objective of this study was to identify biological processes that are altered during ageing in the hippocampus and that modify Ad risk and lifespan, and then to identify putative gene drivers of these programmes. We integrated common human genetic variation associated with human lifespan or Ad from genome-wide association studies with co-expression transcriptome networks altered with age in the mouse and human hippocampus. Our work confirmed that genetic variation associated with Ad was enriched in gene networks expressed by microglia responding to ageing and revealed that they were also enriched in an oligodendrocytic gene network. Compellingly, longevity-associated genetic variation was enriched in a gene network expressed by homeostatic microglia whose expression declined with age. The genes driving this enrichment include CASP8 and STAT3, highlighting a potential role for these longevity-associated genes in the homeostatic functions of innate immune cells, and these genes might drive 'inflammageing'. Thus, we observed that gene variants contributing to ageing and AD balance different aspects of microglial and oligodendrocytic function. Furthermore, we also highlight putative Ad risk genes, such as LAPTM5, ITGAM and LILRB4, whose association with Ad falls below genome-wide significance but show strong co-expression with known Ad risk genes in these networks. Indeed, five of the putative risk genes highlighted by our analysis, ANKH, GRN, PLEKHA1, SNX1 and UNC5CL, have subsequently been identified as genome-wide significant risk genes in a subsequent genome-wide association study with larger sample size, validating our analysis. This work identifies new genes that influence ageing and AD pathogenesis, and highlights the importance of microglia and oligodendrocytes in the resilience of the brain against ageing and AD pathogenesis. Our findings have implications for developing markers indicating the physiological age of the brain and new targets for therapeutic intervention.

Sex and education differences in trajectories of physiological ageing: longitudinal analysis of a prospective English cohort study.

Physiological age (PA) derived from clinical indicators including blood-based biomarkers and tests of physiological function can be compared with chronological age to examine disparities in health between older adults of the same age. Though education interacts with sex to lead to inequalities in healthy ageing, their combined influence on longitudinally-measured PA has not been explored. We derived PA based on longitudinally-measured clinical indicators and examined how sex and education interact to inform PA trajectories. Three waves of clinical indicators (2004/05-2012/13) drawn from the English Longitudinal Study of Ageing (ages 50-100 years) were used to estimate PA, which was internally validated by confirming associations with incident chronic conditions, functional limitations, and memory impairment after adjustment for chronological age and sex. Joint models were used to construct PA trajectories in 8,891 ELSA participants to examine sex and educational disparities in PA. Among the least educated participants, there were negligible sex differences in PA until age 60 (sex difference [men-women] age 50=-0.6 years [95% confidence interval=-2.2-0.6]; age 60=0.4 [-0.6-1.4]); at age 70, women were 1.5 years (0.7-2.2) older than men. Among the most educated participants, women were 3.8 years (1.6-6.0) younger than men at age 50, and 2.7 years (0.4-5.0) younger at age 60, with a non-significant sex difference at age 70. Higher education provides a larger midlife buffer to physiological ageing for women than men. Policies to promote gender equity in higher education may contribute to improving women's health across a range of ageing-related outcomes.

Accelerated Biological Aging Increases the Risk of Short- and Long-term Stroke Prognosis in Patients with Ischemic Stroke or TIA

Biological age (BA), an integrated measure of physiological aging, has a clear link to stroke. There is a paucity of long-term longitudinal studies about the association between accelerated biological age and stroke prognosis in patients with previous strokes, and the differences in the predictive ability of various BA indicators calculated from clinical biochemistry biomarkers for future stroke outcomes are still unknown. To evaluate the role of three accelerated BA indicators for short- and long-term prognosis of patients with ischemic stroke or transient ischemic attack (TIA), and to identify the most appropriate predictor. This study included 7396 patients from the Third China National Stroke Registry (CNSR-III), a prospective national registry of patients with acute ischemic stroke or TIA between August 2015 and March 2018 in China. We constructed accelerated BA using three widely recognized algorithms: PhenoAge, Klemera-Doubal, and HD method. To ascertain the association of accelerated BA with the risk of short- and long-term stroke outcomes, a Cox or logistic regression model was conducted for the analysis. The net reclassification index and integrated discrimination improvement were used to evaluate the added model improvement ability of BA acceleration. Compared to those with the lowest of PhenoAge acceleration, patients with the highest were more likely to have a higher risk of stroke (HR 1.98, 95% CI 1.49-2.63, P<0.001), ischemic stroke (HR 1.88, 95% CI 1.41-2.53, P<0.001), composite vascular events (HR 2.03, 95% CI 1.53-2.68, P<0.001), all-cause death (HR 7.02, 95% CI 3.41-14.47, P<0.001) and the modified Rankin scale of 3-6 (OR 2.55, 95% CI 2.05-3.16, P<0.001) at three months, and the association observed within one year and five years was similar to that within three months. The risk of all stroke outcomes for HDAge was consistent with PhenoAge acceleration, but KDMAge acceleration was the same, except for stroke within one year (HR 1.24, 95% CI 1.00-1.53, P=0.053). PhenoAge acceleration provided a better improvement in the model's predictive ability for stroke prognosis, compared to BA determined by other algorithms. In this prospective cohort study, BA acceleration, particularly PhenoAge, may help identify stroke patients with risks of short- and long-term poor outcomes, potentially enabling subclinical prevention and early intervention. This work was supported by grants from Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-029), the National Natural Science Foundation of China (U20A20358), Beijing Hospitals Authority Clinical Medicine Development of special funding support (ZLRK202312), the National Key R&D Program of China (No. 2022YFC3602500, 2022YFC3602505), Outstanding Young Talents Project of Capital Medical University (A2105), and Beijing High-Level Public Health Technical Personnel Construction Project (Discipline leader -03-12).

Exploring Sleep Quality and Attitudes in Ageing Portuguese Population

Sleep disturbances are prevalent among older adults, often due to natural physiological aging or various mental health factors, including beliefs and attitudes toward sleep. Despite this, the relationship between sleep quality and mental well-being in older populations remains underexplored. This study aims to examine the role of dysfunctional beliefs and attitudes about sleep as predictors of poor sleep quality in Portuguese adults aged 50 and above. The study included 125 Portuguese participants, aged 50 to 80 (M = 58.07, SD = 6.15). Data were collected using the Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16), the Pittsburgh Sleep Quality Index (PSQI), and the Work Health Questionnaire (WHQ), along with sociodemographic information. A self-report online survey was disseminated through social media between March and May 2024. Findings indicate a significant association between negative beliefs about sleep, poor perceptions of health, and decreased sleep quality in adults over 50. These relationships intensify with age, suggesting that negative attitudes toward sleep may exacerbate sleep disturbances. The results highlight the need to better understand the interplay between sleep beliefs, functional health, and sleep quality in older populations. Such understanding can inform the development of interventions to improve sleep literacy and overall well-being among older adults.

Age-Related Decline in Disengaging Spatial Attention in Physiological Aging.

Background/Objectives: Attention is a complex process involving various components such as alerting, orienting, and resolving conflicts. These components have been widely examined using the Attention Network Test (ANT), which has also been used to explore attentional decline associated with aging. However, discrepancies exist in the literature regarding which specific aspects of attention are most impacted by aging. These inconsistencies could be due to methodological issues such as group comparisons that may exaggerate differences between groups while flattening subtle variations within groups. Methods: To address this issue, we administered the ANT to 60 healthy participants aged between 62 and 90 years. Using a multivariate regression analysis, we examined whether increasing age was associated with changes in alerting, orienting, and conflict resolution, while controlling for overall performance in terms of both reaction times and accuracy. Results: The results showed a general and age-insensitive decline in two of the three attentional components: the alerting effect, which was abolished, and a large conflict effect, which was present regardless of age. In contrast, the orienting of spatial attention was found to linearly increase with increasing age. More focused analyses revealed that the ability to shift attention from the central (initial) to the peripheral (target) location slowed down as a function of age. Conclusions: These results suggest that aging is associated with a greater difficulty in disengaging endogenous attention from the central, uninformative cue to direct attention on task-relevant peripheral targets.

Placental and Fetal Metabolic Reprogramming in Pregnancies with Intrauterine Growth Restriction.

The high-altitude hypoxia model demonstrates that insufficiently oxygenated placentas activate compensatory mechanisms to ensure fetal survival, hinging on the transcription factor hypoxia-inducible factor-1. The aim of the present study is to investigate whether and when similar mechanisms are also activated during intrauterine growth restriction (IUGR). A retrospective observational study evaluated a series of umbilical cord blood samples, which provide a realistic representation of the fetal intrauterine status, collected from a cohort of preterm and term neonates, both affected and not affected by IUGR. Results demonstrate that preterm IUGR fetuses receive a lower supply of oxygen and glucose from the placenta, along with a greater provision of lactate and carbon dioxide compared to non-IUGR neonates. Simultaneously, preterm IUGR fetuses increase oxygen extraction and reduce lactate production. These differences between IUGR and non-IUGR placentas and fetuses disappear as the term of pregnancy approaches. In conclusion, this study suggests that hypoperfused placentas in preterm pregnancies with IUGR activate a metabolic reprogramming aimed at favoring glycolytic metabolism to ensure fetal oxygenation, even though the availability of glucose for the fetus is reduced. Consequently, preterm IUGR fetuses activate gluconeogenetic metabolic reprogramming, despite it being energetically expensive. These metabolic adaptations disappear in the last weeks of pregnancy, likely due to physiological placental aging that increases the fetoplacental availability of oxygen. Placental oxygenation appears to be the main driver of metabolic reprogramming; however, further studies are necessary to identify the underlying biological mechanisms modulated by oxygen.

Neuroanatomical and clinical correlates of prodromal dementia with Lewy bodies: a systematic literature review of neuroimaging findings.

Prodromal Dementia with Lewy bodies (pro-DLB) has been recently defined; however, the neuroanatomical and functional correlates of this stage have not yet been univocally established. This study aimed to systematically review neuroimaging findings focused on pro-DLB. A literature search of works employing MRI, PET, and SPECT was performed. Forty records were included: 15 studies assessed gray matter (GM) and white matter (WM) integrity, and 31 investigated metabolism, perfusion, and resting-state connectivity. Results showed that, in pro-DLB, frontal lobe areas were characterized by decreased function, cortical atrophy, and WM damage. Volumetric reductions were found in the insula, which also showed heightened metabolism. A pattern of hypofunction and structural damage was observed in the lateral and ventral temporal lobe; instead, the parahippocampal cortex and hippocampus exhibited greater function. Hypofunction marked parietal and occipital regions, with additional atrophy in the medial occipital lobe and posterior parietal cortex. Subcortically, atrophy and microstructural damage in the nucleus basalis of Meynert were reported, and dopamine transporter uptake was reduced in the basal ganglia. Overall, structural and functional damage was already present in pro-DLB and was coherent with the possible clinical onset. Frontal and parieto-occipital alterations may be associated with deficits in attention and executive functions and in visuo-perceptual/visuo-spatial abilities, respectively. Degeneration of cholinergic and dopaminergic transmission appeared substantial at this disease stage. This review provided an updated and more precise depiction of the brain alterations that are specific to pro-DLB and valuable to its differentiation from physiological aging and other dementias.

Similarities and differences in the gene expression signatures of physiological age versus future lifespan.

Across all taxa of life, individuals within a species exhibit variable lifespans. Differences in genotype or environment are not sufficient to explain this variance, as even isogenic Caenorhabditis elegans nematodes reared under uniform conditions show significant variability in lifespan. To investigate this phenomenon, we used lifespan-predictive biomarkers to isolate, at mid-adulthood, prospectively long- and short-lived individuals from an otherwise identical population. We selected two biomarkers which correlated positively with lifespan, lin-4p::GFP and mir-243p::GFP, and two which correlated negatively, mir-240/786p::GFP and autofluorescence. The gene-expression signature of long versus short future lifespan was strikingly similar across all four biomarkers tested. Since these biomarkers are expressed in different tissues, these results suggest a shared connection to a global health state correlated with future lifespan. To further investigate this underlying state, we compared the transcriptional signature of long versus short future lifespan to that of chronologically young versus old individuals. By comparison to a high-resolution time series of the average aging transcriptome, we determined that subpopulations predicted to be long- or short-lived by biomarker expression had significantly different transcriptional ages despite their shared chronological age. We found that this difference in apparent transcriptional age accounted for the majority of differentially expressed genes associated with future lifespan. Interestingly, we also identified several genes whose expression consistently separated samples by biomarker expression independent of apparent transcriptional age. These results suggest that the commonalities in the long-lived versus short-lived state reported across different biomarkers of aging extends beyond simply transcriptionally young versus transcriptionally old.

Potential of Anthocyanin-rich Products to Prevent and Improve Endothelial Function and Senescence: Focus on Anthocyanins.

Endothelial dysfunction is a pivotal early event in the development of major cardiovascular diseases including hypertension, atherosclerosis, diabetes, and aging. The alteration of the endothelial function is often triggered by an imbalance between the endothelial formation of vasoprotective factors, including nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH), and vasocontracting factors, such as arachidonic acid-derived mediators generated by cyclooxygenases, and an increased level of oxidative stress. Recently, endothelial senescence was reported to be an early trigger of endothelial dysfunction. Preclinical studies indicate that polyphenol-rich food, including anthocyanin-rich products, can activate pathways promoting an increased formation of vasoprotective factors and can prevent the induction of endothelial dysfunction in endothelial cells and isolated blood vessels. Similarly, intake of anthocyanin-rich products has been associated with the prevention and/or the improvement of an endothelial dysfunction in several experimental models of cardiovascular diseases, including physiological aging. Moreover, clinical data indicate that polyphenol-rich and anthocyanin-rich products can improve endothelial function and vascular health in humans with cardiovascular diseases. The present review will discuss both experimental and clinical evidence indicating that several polyphenol-rich foods and natural products, and especially anthocyanin-rich products, can promote endothelial and vascular health, as well as the underlying mechanisms.

Oxygen-dependent alternative mRNA splicing and a cone-specific motor protein revealed by single-cell RNA sequencing in hypoxic retinas

Restricted oxygen supply in the aging eye may lead to hypoxic conditions in the outer retina and contribute not only to physiological aging but also to nonhereditary degenerative retinal diseases. To understand the hypoxic response of specific retinal cell types, we performed single-cell RNA sequencing of retinas isolated from mice exposed to hypoxia. Significantly upregulated expression of marker genes in hypoxic clusters confirmed a general transcriptional response to hypoxia. By focusing on the hypoxic response in photoreceptors, we identified and confirmed a kinesin motor protein (Kif4) that was specifically and strongly induced in hypoxic cones. In contrast, RNA-binding proteins Rbm3 and Cirbp were differentially expressed across clusters but demonstrated isoform switching in hypoxia. The resulting short variants of these gene transcripts are connected to epitranscriptomic regulation, a notion supported by the differential expression of writers, readers and erasers of m6A RNA methylations in the hypoxic retina. Our data indicate that retinal cells adapt to hypoxic conditions by adjusting their transcriptome at various levels including gene expression, alternative splicing and the epitranscriptome. Adaptational processes may be cell-type specific as exemplified by the cone-specific upregulation of Kif4 or general like alternative splicing of RNA binding proteins.

Engineering extracellular vesicles to transiently permeabilize the blood–brain barrier

BackgroundDrug delivery to the brain is challenging due to the restrict permeability of the blood brain barrier (BBB). Recent studies indicate that BBB permeability increases over time during physiological aging likely due to factors (including extracellular vesicles (EVs)) that exist in the bloodstream. Therefore, inspiration can be taken from aging to develop new strategies for the transient opening of the BBB for drug delivery to the brain.ResultsHere, we evaluated the impact of small EVs (sEVs) enriched with microRNAs (miRNAs) overexpressed during aging, with the capacity to interfere transiently with the BBB. Initially, we investigated whether the miRNAs were overexpressed in sEVs collected from plasma of aged individuals. Next, we evaluated the opening properties of the miRNA-enriched sEVs in a static or dynamic (under flow) human in vitro BBB model. Our results showed that miR-383-3p-enriched sEVs significantly increased BBB permeability in a reversible manner by decreasing the expression of claudin 5, an important tight junction protein of brain endothelial cells (BECs) of the BBB, mediated in part by the knockdown of activating transcription factor 4 (ATF4).ConclusionsOur findings suggest that engineered sEVs have potential as a strategy for the temporary BBB opening, making it easier for drugs to reach the brain when injected into the bloodstream.Graphical abstract