The genetic advantage of healthy centenarians: unraveling the central role of NLRP3 in exceptional healthspan.

Despite extensive research into extending human healthspan (HS) and compressing morbidity, the mechanisms underlying aging remain elusive. However, a better understanding of the genetic advantages responsible for the exceptional HS of healthy centenarians (HC), who live in good physical and mental health for one hundred or more years, could lead to innovative health-extending strategies. This review explores the role of NLRP3, a critical component of innate immunity that significantly impacts aging. It is activated by pathogen-associated signals and self-derived signals that increase with age, leading to low-grade inflammation implicated in age-related diseases. Furthermore, NLRP3 functions upstream in several molecular aging pathways, regulates cellular senescence, and may underlie the robust health observed in HC. By targeting NLRP3, mice exhibit a phenotype akin to that of HC, the HS of monkeys is extended, and aging symptoms are reversed in humans. Thus, targeting NLRP3 could offer a promising approach to extend HS. Additionally, a paradigm shift is proposed. Given that the HS of the broader population is 30 years shorter than that of HC, it is postulated that they suffer from a form of accelerated aging. The term 'auto-aging' is suggested to describe accelerated aging driven by NLRP3.

Research on the Thermal Aging Mechanism of Polyvinyl Alcohol Hydrogel.

Polyvinyl alcohol (PVA) hydrogels find applications in various fields, including machinery and tissue engineering, owing to their exceptional mechanical properties. However, the mechanical properties of PVA hydrogels are subject to alteration due to environmental factors such as temperature, affecting their prolonged utilization. To enhance their lifespan, it is crucial to investigate their aging mechanisms. Using physically cross-linked PVA hydrogels, this study involved high-temperature accelerated aging tests at 60 °C for 80 d and their performance was analyzed through macroscopic mechanics, microscopic morphology, and microanalysis tests. The findings revealed three aging stages, namely, a reduction in free water, a reduction in bound water, and the depletion of bound water, corresponding to volume shrinkage, decreased elongation, and a "tough-brittle" transition. The microscopic aging mechanism was influenced by intermolecular chain spacing, intermolecular hydrogen bonds, and the plasticizing effect of water. In particular, the loss of bound water predominantly affected the lifespan of PVA hydrogel structural components. These findings provide a reference for assessing and improving the lifespan of PVA hydrogels.

Neuropeptides regulate embryonic salivary gland branching through the FGF/FGFR pathway in aging klotho-deficient mice.

Salivary gland branching morphogenesis is regulated by the functional integration of neuronal signaling, but the underlying mechanisms are not fully understood in aging accelerated klotho-deficient (Kl-/-) mice. Here, we investigated whether the neuropeptides substance P (SP) and neuropeptide Y (NPY) affect the branching morphogenesis of embryonic salivary glands in aging Kl-/- mice. In the salivary glands of embryonic Kl-/- mice, morphological analysis and immunostaining revealed that epithelial bud formation, neuronal cell proliferation/differentiation, and the expression of the salivary gland functional marker ZO-1 were decreased in embryonic ductal cells. Incubation with SP/NPY at E12-E13d promoted branching morphogenesis, parasympathetic innervation, and epithelial proliferation in salivary glands of embryonic Kl-/- mice. The ERK inhibitor U0126 specifically inhibited neuronal substance-induced epithelial bud formation in the embryonic salivary gland. RNA-seq profiling analysis revealed that the expression of fibroblast growth factors/fibroblast growth factors (FGFs/FGFRs) and their receptors was significantly regulated by SP/NPY treatment in the embryonic salivary gland (E15). The FGFR inhibitor BGJ389 inhibited new branching formation induced by SP and NPY treatment and ERK1/2 expression. These results showed that aging may affect virtually the development of salivary gland by neuronal dysfunction. The neuropeptides SP/NPY induced embryonic salivary gland development through FGF/FGFR/ERK1/2-mediated signaling.

Model of Accelerated Aging in CB6F2 Mice Induced by Ionizing Radiation.

A model for accelerated aging in mice was developed: CB6F2 mice aged 39-45 days were exposed to fractionated 4-fold relatively uniform γ-radiation (137Cs, 0.98 Gy/min) at a total dose of 6.8 Gy. Radiation exposure led to delayed active growth, leukopenia, and lymphopenia for over 1 year during the post-radiation period. The death of irradiated males and females occurred significantly earlier than in control group animals. Median lifespans in the experimental group were 35-38% lower than in the control group (p<0.001). Ionizing radiation exposure led to the early development of hair depigmentation, cachexia, and the development of aging-associated diseases. In irradiated mice, oncological pathology constituted 30-35% in the mortality structure, which is twice as often as in the control group. The developed model can be used to study the pathogenesis of accelerated aging under radiation exposure and the search for means of its prevention and treatment.

Cystathionine γ-lyase inhibits mitochondrial oxidative stress by releasing H2S nearby through the AKT/NRF2 signaling pathway.

Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (H2S). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing H2S nearby under stress conditions. We found that H2S partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway. H2S improved mitochondrial function by altering the expressions of the mitofusin2 and dynamin-1-like mitochondrial fission proteins to inhibit oxidative stress and enhance NRF2 nuclear translocation. CSE is located only in the cytoplasm and not in the mitochondria, but it is transported to the vicinity of the mitochondria to produce H2S, which plays an antioxidant role in human umbilical vein endothelial cells under stress. The CSE mutant (with mutated CSE activity center: CSED187A) partially decreased the effects on promoting angiogenesis, resisting oxidative stress, and entering the mitochondria. These results show that CSE translocation is a unique mechanism that promotes H2S production inside the mitochondria under stress stimulation. Therefore, the CSE mutant site (CSED187A) may be a potential target for drug therapy.

[Demographic and professional risks of depopulation among working population in Russia: 14 years later (analytical review).]

The article presents a comparative analysis of the process of population aging in the context of demographic and professional risks of depopulation among working population in Russia. The values of the main medical and demographic indicators of population aging for Russia and developed countries were given. The results of UN forecasts, probabilistic forecasts of the total number and some characteristics of the age-sex structure for the population of the Russian Federation were analyzed. The state of demographic disadvantage in Russia and in the world was convincingly shown. Particular attention was paid to the consideration of the demographic risks of a reduction in the working-age population and an increase in the burden on the working-age population. The need for further research on the use of geroprotectors and modern gerontotechnologies as means and methods for preventing premature decline in work ability, slowing down the aging process of workers, reducing the mortality rate among working population and increasing professional longevity has been proven.

Accelerated aging behavior of degradable and non-degradable microplastics via advanced oxidation and their adsorption characteristics towards tetracycline.

The increasing global utilization of biodegradable plastics due to stringent regulations on traditional plastics has caused a significant rise in microplastic (MPs) pollution in aquatic ecosystems from biodegradable products. However, the environmental behavior of biodegradable MPs remains inadequately elucidated. This study explored the aging processes of polylactic acid (PLA) and polystyrene (PS) under a heat-activated potassium persulfate (K2S2O8) system, as well as their adsorption characteristics towards tetracycline (TCs). In comparison to PS, the surface structure of PLA experienced more pronounced changes over aging, exhibiting evident pits, cracks, and fragmentation. The carbonyl index (CI) and oxygen/carbon ratio (O/C) of PS displayed exponential growth over time, whereas the values for PLA showed linear and exponential increases, respectively. The adsorption capacity of TCs by PS and PLA aged for 6 days increased from 0.312 mg‧g-1 and 0.457 mg‧g-1for original PS and PLA, respectively, to 0.372 mg‧g-1 and 0.649 mg‧g-1. Meanwhile, the adsorption rate (k2 values) for TCs decreased by 42.03 % for PS and 79.64 % for PLA compared to their initial values. The findings indicated that biodegradable PLA-MPs may exhibit higher tetracycline carrying capacities than PS, potentially increasing environmental and organismal risks, particularly in view of aging effects.

Association between Accelerated Biological Aging, Diet, and Gut Microbiome.

Factors driving accelerated biological age (BA), an important predictor of chronic diseases, remain poorly understood. This study focuses on the impact of diet and gut microbiome on accelerated BA. Accelerated Klemera-Doubal biological age (KDM-BA) was estimated as the difference between KDM-BA and chronological age. We assessed the cross-sectional association between accelerated KDM-BA and diet/gut microbiome in 117 adult participants from the 10,000 Families Study. 16S rRNA sequencing was used to estimate the abundances of gut bacterial genera. Multivariable linear mixed models evaluated the associations between accelerated KDM-BA and diet/gut microbiome after adjusting for family relatedness, diet, age, sex, smoking status, alcohol intake, and BMI. One standard deviation (SD) increase in processed meat was associated with a 1.91-year increase in accelerated KDM-BA (p = 0.04), while one SD increase in fiber intake was associated with a 0.70-year decrease in accelerated KDM-BA (p = 0.01). Accelerated KDM-BA was positively associated with Streptococcus and negatively associated with Subdoligranulum, unclassified Bacteroidetes, and Burkholderiales. Adjustment for gut microbiome did not change the association between dietary fiber and accelerated KDM-BA, but the association with processed meat intake became nonsignificant. These cross-sectional associations between higher meat intake, lower fiber intake, and accelerated BA need validation in longitudinal studies.

Chemical Structure and Thermal Properties versus Accelerated Aging of Bio-Based Poly(ether-urethanes) with Modified Hard Segments.

Aging of polymers is a natural process that occurs during their usage and storage. Predicting the lifetime of polymers is a crucial aspect that should be considered at the design stage. In this paper, a series of bio-based thermoplastic poly(ether-urethane) elastomers (bio-TPUs) with modified hard segments were synthesized and investigated to understand the structural and property changes triggered by accelerated aging. The bio-TPUs were synthesized at an equimolar ratio of reagents using the prepolymer method with the use of bio-based poly(trimethylene ether) glycol, bio-based 1,3-propanediol, and hexamethylene diisocyanate or hexamethylene diisocyanate/partially bio-based diisocyanate mixtures. The polymerization reaction was catalyzed by dibutyltin dilaurate (DBTDL). The structural and property changes after accelerated aging under thermal and hydrothermal conditions were determined using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic mechanical thermal analysis (DMTA). Among other findings, it was observed that both the reference and aged bio-TPUs decomposed in two main stages and exhibited thermal stability up to approximately 300 °C. Based on the research conducted, it was found that accelerated aging impacts the supramolecular structure of TPUs.

Does BioAge identify accelerated aging in individuals with bipolar disorder? An exploratory study in the FACE-BD cohort.

BACKGROUND: Individuals with bipolar disorders (BD) have an estimated loss of life expectancy around 10-15 years. Several laboratory-measured biomarkers of accelerated aging exist (e.g., telomere length), however with a questionable transferability to bedside. There is a need for easily and inexpensively measurable markers of aging, usable in routine practice, such as BioAge. METHODS: We calculated BioAge that estimates biological age based on routine blood tests and a physical exam, in a sample of 2220 outpatients with BD. We investigated associations between BioAge Acceleration (BioAgeAccel), which is an indicator of accelerated aging, and sociodemographic variables, clinical variables, and current psychotropic medication use. RESULTS: Mean chronological age was 40.2 (±12.9). Mean BioAge was 39.1 (±12.4). Mean BioAgeAccel was 0.08 (±1.8). A minority of individuals (15%) had a BioAgeAccel above 2 years. Multivariable analyses suggested strong associations between a higher BioAgeAccel and younger age, male sex, overweight and sleep disturbances. Regarding current psychotropic medication use, discrepancies between univariate and multivariate analyses were observed. CONCLUSIONS: A minority of individuals with BD had an accelerated aging as measured by BioAge. We identified associations with potentially modifiable factors, such as higher body mass index and sleep disturbances, that are however nonspecific to BD. These results require replications in independent samples of individuals with BD, and comparisons with a control group matched for age and gender. Longitudinal studies are also required to test whether any change in metabolic health, or sleep might decrease BioAgeAccel.

Degradation of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Reinforced with Regenerated Cellulose Fibers.

PHBV is a promising plastic for replacing conventional petroleum-based plastics in the future. However, the mechanical properties of PHBV are too low for use in high-stress applications and the degradation of the polymer limits possible applications. In this work, the mechanical properties were, therefore, increased using bio-based regenerated cellulose fibers and degradation processes of the PHBV-RCF composites were detected in accelerated aging tests under various environmental conditions. Mechanical, optical, rheological and thermal analysis methods were used for this characterization. The fibers significantly increased the mechanical properties, in particular the impact strength. Different degradation mechanisms were identified. UV radiation caused the test specimens to fade significantly, but no reduction in mechanical properties was observed. After storage in water and in aqueous solutions, the mechanical properties of the compounds were significantly reduced. The reason for this was assumed to be hydrolytic degradation catalyzed by higher temperatures. The hydrolytic degradation of PHBV was mainly caused by erosion from the test specimen surface. By exposing the regenerated cellulose fibers, this effect could now also be visually verified. For the use of regenerated cellulose fiber-reinforced PHBV in more durable applications, the aging mechanisms that occur must be prevented in the future through the use of stabilizers.

Association of visceral adiposity index with phenotypic age acceleration: insight from NHANES 1999-2010.

BACKGROUND: Obesity correlates with accelerated aging. This study aims to investigate the association between the visceral adiposity index (VAI) and accelerated aging. METHODS: Biological aging was evaluated by phenotypic age acceleration (PhenoAgeAccel). Utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2010, we employed weighted multivariable logistic regression models, along with subgroup analysis, to examine the association between VAI and PhenoAgeAccel. Moreover, smooth curve fitting was utilized to identify potential nonlinear association, complemented by a two-piece linear regression model to investigate threshold effects. RESULTS: Of the included 11,340 participants aged 20 years and older, the mean (95% CI) age was 46.569 (45.946, 47.191) years, and 49.189% were male. The mean (95% CI) VAI for all participants was 2.176 (2.114, 2.238), and the mean (95% CI) PhenoAgeAccel was -6.306 (-6.618, -5.994) years. In the fully adjusted model, each incremental unit increase of VAI was associated with a 0.312-year increase in PhenoAgeAccel (ß = 0.312, 95% CI: 0.217, 0.408). This positive association was more statistically significant among individuals with cancer. Furthermore, a segmented association was observed between VAI and PhenoAgeAccel, with a turning point identified at 10.543. Below this threshold, VAI exhibited a positive correlation with PhenoAgeAccel (ß = 0.617, 95% CI: 0.499, 0.735), while beyond it, the association became nonsignificant. CONCLUSION: This study demonstrated a positive association between VAI and accelerated aging within a nationally representative population. The findings suggest that controlling adiposity may exert anti-aging effects and help prevent aging-related diseases.

Functional limitations among adult cancer survivors in the United States.

PURPOSE: Using data from the National Health Interview Survey (NHIS), this study examined the odds of functional limitations across nine domains by cancer status (with vs. without cancer history) and age group (18-44, 45-64, 65 + years). METHODS: Participants were 151,509 adults in the 2014-2018 NHIS. Functional limitations included self-reported difficulty conducting nine activities. Data were analyzed using age-stratified multivariate logistic regression (no limitation vs. limited in any way; minor limitation vs. major limitation) and are reported as covariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). To gather insight on the influence of cancer, compared to aging without a history of cancer, on functional limitations, we also conducted exploratory regression analyses comparing all cancer by age groups to 18-44 year-olds without a cancer history. RESULTS: Cancer survivors (n = 12,518) were more likely to report a limitation than adults without cancer (n = 138,991). Age-stratified ORs for 1 + limitation were 2.75 (95% CI 1.98, 3.81) among 18-44 year-olds, 2.42 (95% CI 2.00, 2.93) among 45-64 year-olds, and 1.59 (95% CI 1.39, 1.82) among 65 + year-olds. Cancer survivors were more likely to report major limitations across multiple domains, with age-stratified ORs ranging from 1.18 (65 + year-olds, stooping limitation) to 2.28 (18-44 year-old, sitting limitation). ORs from exploratory analyses were lowest among 45-64 year-old adults without a cancer history (2.69-4.42) and highest among older adult cancer survivors (3.42-14.73). CONCLUSIONS: Cancer was associated with limitations across age groups, with the highest age-stratified ORs observed among younger adults and for mobility and lower-extremity limitations. Stronger efforts to assess limitations as part of routine care and implement targeted interventions to address limitations are needed. IMPLICATIONS FOR CANCER SURVIVORS: Functional limitations have been linked with poorer aging trajectories and lower quality of life in cancer and non-cancer populations. Routine screening to identify and discuss functional limitations with cancer patients may help reduce the burden of such limitations on survivors.

Intricacies of aging and Down syndrome.

Down syndrome is the most frequently occurring genetic condition, with a substantial escalation in risk associated with advanced maternal age. The syndrome is characterized by a diverse range of phenotypes, affecting to some extent all levels of organization, and its progeroid nature - early manifestation of aspects of the senile phenotype. Despite extensive investigations, many aspects and mechanisms of the disease remain unexplored. The current review aims to provide an overview of the main causes and manifestations of Down syndrome, while also examining the phenomenon of accelerated aging and exploring potential therapeutic strategies.

Maximizing Insights from Longitudinal Epigenetic Age Data: Simulations, Applications, and Practical Guidance.

Background: Epigenetic Age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk. Limited by available data, most studies investigating these relationships have been cross-sectional - using a single EA measurement. However, the recent growth in longitudinal DNAm studies has led to analyses of associations with EA over time. These studies differ in (i) their choice of model; (ii) the primary outcome (EA vs. EAA); and (iii) in their use of chronological age or age-independent time variables to account for the temporal dynamic. We evaluated the robustness of each approach using simulations and tested our results in two real-world examples, using biological sex and birthweight as predictors of longitudinal EA. Results: Our simulations showed most accurate effect sizes in a linear mixed model or generalized estimating equation, using chronological age as the time variable. The use of EA versus EAA as an outcome did not strongly impact estimates. Applying the optimal model in real-world data uncovered an accelerated EA rate in males and an advanced EA that decelerates over time in children with higher birthweight. Conclusion: Our results can serve as a guide for forthcoming longitudinal EA studies, aiding in methodological decisions that may determine whether an association is accurately estimated, overestimated, or potentially overlooked.

Plasma neurofilament light protein is differentially associated with age in individuals with treatment-resistant schizophrenia and bipolar affective disorder compared to controls.

Accelerated brain ageing has been observed in multiple psychiatric disorders. This study examined whether relationships between age and plasma neurofilament light (NfL) protein differed in individuals with psychiatric disorders (major depressive disorder (n = 42), bipolar affective disorder (n = 121), treatment-resistant schizophrenia (TRS, n = 82)) compared to two healthy control (HC) groups (n = 1,926 and n = 59). Compared to two independent HC samples, individuals with TRS demonstrated a stronger positive relationship between age and NfL levels. Individuals with BPAD had a stronger negative relationship between age and NfL levels compared to the large normative HC cohort, but not locally-acquired HCs. These findings show that plasma NfL levels are differentially associated with age in individuals with TRS and BPAD compared to healthy individuals.

Carvacrol prevents D-( +)-galactose-induced aging-associated erectile dysfunction by improving endothelial dysfunction and oxidative stress in rats.

Aging is one of the risk factors involved in the development of erectile dysfunction (ED). Growing evidence suggests that oxidative stress is the critical mediator of changes in endothelial function and penile vascular tone in the aging process. Thus, reducing reactive oxygen species (ROS) levels may preserve the bioactivity of the penile vasculature. Antioxidant compounds, such as carvacrol, limit the damage caused by ROS and, therefore, benefit the treatment of ED. Thus, this study aims to evaluate the effects of carvacrol on ED using the D-( +)-galactose aging model. The animals were divided into five groups: control, D-( +)-galactose 150 mg/kg, carvacrol 50 mg/kg or 100 mg/kg, and sildenafil 1.5 mg/kg treated daily for 8 weeks. The physiological, functional, and morphological characteristics of aging-associated ED were evaluated after treatment with carvacrol. Carvacrol prevented ED in a D-( +)-galactose-induced aging model by reducing hypercontractility, enhancing endothelial dysfunction in the rat corpus cavernosum, and improving endothelial health of rat cavernous endothelial cells. In addition, carvacrol prevented the destruction of erectile components essential for penile erection and promoted a reduction of penile tissue senescence, probably through mechanisms that involve the harmful modulation of oxidative stress. Carvacrol significantly improved the erectile function of rats in a D-( +)-galactose-induced aging model and has excellent potential as a new therapeutic alternative in treating erectile dysfunction.

Longitudinal Analysis of Renal Function Changes in Elderly Populations: Health Status Evaluation and Risk Factor Assessment.

Background: This study aims to investigate GFR decline in elderly subjects with varying physical conditions and analyze key risk factors impacting renal function changes. Methods: We obtained data from patients between 2017 and 2019, and matched healthy elderly subjects based on gender and age. Data collected for all subjects included annual measurements of fast blood glucose (GLU), glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-c), blood albumin (ALB), blood uric acid (UA), urine protein (UP), and systolic blood pressure (SBP). Additionally, information on coexisting diseases was gathered. The Full Age Spectrum (FAS) equation was used to calculate eGFR. Results: A total of 162 patients with complete 3-year renal dynamic imaging were included, including 84 patients in the kidney disease group (K group) and 78 patients in the non-kidney disease group (NK group). Ninety individuals were selected as the healthy group (H group). The annual decline rate in the K group was the fastest, which exceeded 5mL/min/1.73m2 (P < 0.05). Group (K group: ß=-40.31, P<0.001; NK group: ß=-26.96, P<0.001), ALB (ß=-0.38, P=0.038) and HbA1c (ß=1.36, P=0.029) had a significant negative impact on the eGFR changes. For participants who had negative proteinuria: K group had the most significant annual eGFR decline. Conclusion: The presence of kidney disease, along with proteinuria nor not, can lead to a marked acceleration in kidney function decline in elderly. We categorize elderly individuals with an annual eGFR decline of more than 5 mL/min/1.73m2 as the "kidney accelerated aging" population.

Social Determinants of Health and Biological Age among Diverse U.S. Adults, NHANES 2011-2018.

We examined the sex-specific association between education and income with biological age (BA) and by race/ethnicity. The Klemera-Doubal method was used to calculate BA among 6,213 females and 5,938 males aged 30-75 years who were Hispanic, non-Hispanic (NH) White, NH Black (NHB), or NH Asian (NHA). Compared with a college education, less than a high school education was associated with greater BA by 3.06 years (95% CI: 1.58, 4.54) among females only; associations were strongest among NHB, Hispanic, and NHA females. Compared with an annual income of ≥$75,000, an income <$25,000 was associated with greater BA by 4.95 years (95% CI: 3.42, 6.48) among males and 2.76 years among females (95% CI: 1.51, 4.01); associations were strongest among NHW and NHA adults, and Hispanic males. Targeting upstream sources of structural disadvantage among racial/ethnic minority groups, in conjunction with improvements in income and education, may promote healthy aging in these populations.

Sex as a Determinant of Age-Related Changes in the Brain.

The notion of notable anatomical, biochemical, and behavioral distinctions within male and female brains has been a contentious topic of interest within the scientific community over several decades. Advancements in neuroimaging and molecular biological techniques have increasingly elucidated common mechanisms characterizing brain aging while also revealing disparities between sexes in these processes. Variations in cognitive functions; susceptibility to and progression of neurodegenerative conditions, notably Alzheimer's and Parkinson's diseases; and notable disparities in life expectancy between sexes, underscore the significance of evaluating aging within the framework of gender differences. This comprehensive review surveys contemporary literature on the restructuring of brain structures and fundamental processes unfolding in the aging brain at cellular and molecular levels, with a focus on gender distinctions. Additionally, the review delves into age-related cognitive alterations, exploring factors influencing the acceleration or deceleration of aging, with particular attention to estrogen's hormonal support of the central nervous system.