Visuomotor adaptation across the lifespan.

Being able to adapt our movements to changing circumstances allows people to maintain performance across a wide range of tasks throughout life, but it is unclear whether visuomotor learning abilities are fully developed in young children and, if so, whether they remain stable in the elderly. There is limited evidence of changes in motor adaptation ability throughout life, and the findings are inconsistent. Therefore, our goal was to compare visuomotor learning abilities throughout the lifespan. We used a shorter, gamified experimental task and collected data from participants in 5 age groups. Young children (M = 7 years), older children (M = 11 years), young adults (M = 20 years), adults (M = 40 years) and older adults (M = 67 years) adapted to a 45° visuomotor rotation in a centre-out reaching task. Across measures of rate of adaptation, extent of learning, rate of unlearning, generalization, and savings, we found that all groups performed similarly. That is, at least for short bouts of gamified learning, children and older adults perform just as well as young adults.

The impact of health on labour outcomes among middle-aged and elderly: Insights from India.

The impact of ill-health on labour force participation is a well-recognized concern in both developed and developing countries. However, previous studies have often overlooked age differentials in this relationship, assuming uniform effects across age groups. This study aims to fill this gap by examining how ill-health affects labour outcomes among different age segments in India. Utilizing data from the Longitudinal Ageing Study in India (LASI) Wave 1, which covers over 72,000 individuals aged 45 and above, this research investigates the linkage between health and labour force outcomes. The labour outcomes in this study includes labour force participation, labour earnings and hours worked. Present study used instrumental variable approach to mitigate endogeneity issues and establish causal relationships between health and labour outcomes. The Heckman selection model is utilized to address selection bias in analysing wage and hours worked. The study reveals several key findings. Firstly, ill-health consistently leads to a decline in labour force participation among both middle-aged (28 percent) and elderly (36 percent) individuals in India. This underscores the pervasive impact of health on workforce engagement, particularly in a context with limited social security measures. Secondly, the research identifies significant variations in the effects of ill-health on wages and hours worked based on age. Among elderly individuals, there is a pronounced reduction in both wages and hours worked due to ill-health. However, this effect is less pronounced among middle-aged adults. Furthermore, socioeconomic factors play a pivotal role in shaping how ill-health influences labour outcomes among different age groups. This study underscores the importance of considering age differentials in the impact of ill-health on labour outcomes, offering valuable insights for policymakers, practitioners, and researchers seeking to address this critical issue in India's dynamic socio-economic landscape.

Trajectories in long-term condition accumulation and mortality in older adults: a group-based trajectory modelling approach using the English Longitudinal Study of Ageing.

OBJECTIVES: To classify older adults into clusters based on accumulating long-term conditions (LTC) as trajectories, characterise clusters and quantify their associations with all-cause mortality. DESIGN: We conducted a longitudinal study using the English Longitudinal Study of Ageing over 9 years (n=15 091 aged 50 years and older). Group-based trajectory modelling was used to classify people into clusters based on accumulating LTC over time. Derived clusters were used to quantify the associations between trajectory memberships, sociodemographic characteristics and all-cause mortality by conducting regression models. RESULTS: Five distinct clusters of accumulating LTC trajectories were identified and characterised as: 'no LTC' (18.57%), 'single LTC' (31.21%), 'evolving multimorbidity' (25.82%), 'moderate multimorbidity' (17.12%) and 'high multimorbidity' (7.27%). Increasing age was consistently associated with a larger number of LTCs. Ethnic minorities (adjusted OR=2.04; 95% CI 1.40 to 3.00) were associated with the 'high multimorbidity' cluster. Higher education and paid employment were associated with a lower likelihood of progression over time towards an increased number of LTCs. All the clusters had higher all-cause mortality than the 'no LTC' cluster. CONCLUSIONS: The development of multimorbidity in the number of conditions over time follows distinct trajectories. These are determined by non-modifiable (age, ethnicity) and modifiable factors (education and employment). Stratifying risk through clustering will enable practitioners to identify older adults with a higher likelihood of worsening LTC over time to tailor effective interventions to prevent mortality.

Self-perceptions of aging, physical activity, and depressive symptoms in older community residents with varied neighborhood walkability in Taiwan.

BACKGROUND: Prior research has identified the mediating effect of physical activity in the relationship between self-perceptions of aging and physical health. However, this impact on mental health is unknown, and the influence of environmental contexts proposed by ecological models in this regard remains largely unexplored. Therefore, this study aimed to investigate the role of physical activity in the relationship between self-perceptions of aging and depressive symptoms in older adults, and compare the impact across four levels of neighborhood walkability. METHODS: A sample of 1,055 community-dwelling older adults aged 65 or above was obtained through random-digit-dialing computer-assisted telephone interviewing. The individual's neighborhood walkability was calculated using Walk Score®, and categorized into four levels: car-dependent, somewhat walkable, very walkable, and walker's paradise. Partial least squares structural equation modelling was employed. RESULTS: We found that more positive self-perceptions of aging were associated with fewer depressive symptoms and a mediation effect of physical activity in this relationship. Among the four levels of neighborhood walkability, the mediation effect of physical activity was only statistically significant in the lowest level (car-dependent). The findings supported our hypotheses regarding the mediating effect of self-perceptions of aging on depressive symptoms via physical activity. Neighborhood walkability might potentially influence the mediating role of physical activity. CONCLUSIONS: This study emphasizes key areas on intervention programs and policy formulation to promote mental health in older adults.

Distinctive protein expression in elderly livers in a Sprague-Dawley rat model of normothermic ex vivo liver machine perfusion.

BACKGROUND: Liver grafts are frequently declined due to high donor age or age mismatch with the recipient. To improve the outcome of marginal grafts, we aimed to characterize the performance of elderly vs. young liver grafts in a standardized rat model of normothermic ex vivo liver machine perfusion (NMP). METHODS: Livers from Sprague-Dawley rats aged 3 or 12 months were procured and perfused for 6 h using a rat NMP system or collected as a reference group (n = 6/group). Tissue, bile, and perfusate samples were used for biochemical, and proteomic analyses. RESULTS: All livers cleared lactate during perfusion and continued to produce bile after 6 h of perfusion (614 mg/h). Peak urea levels in 12-month-old animals were higher than in younger animals. Arterial and portal venous pressure, bile production and pH did not differ between groups. Proteomic analysis identified a total of 1477 proteins with oxidoreductase and catalytic activity dominating the gene ontology analysis. Proteins such as aldehyde dehydrogenase 1A1 and 2-Hydroxyacid oxidase 2 were significantly more present in livers of older age. CONCLUSIONS: Young and elderly liver grafts exhibited similar viability during NMP, though proteomic analyses indicated that older grafts are less resilient to oxidative stress. Our study is limited by the elderly animal age, which corresponds to mature but not elderly human age typically seen in marginal human livers. Nevertheless, reducing oxidative stress could be a promising therapeutic target in the future.

Are healthy ageing trajectories suitable to identify rehabilitation needs of the ageing population? An exploratory study using ATHLOS cohort data.

BACKGROUND: The ageing process is highly heterogeneous leading to diverse ageing trajectories. Such trajectories have been modelled to study trends and determinants of ageing and could potentially be used to inform the planning of rehabilitation services at population level. The objective of this paper was to explore whether healthy ageing trajectories are suitable to identify targets for rehabilitation interventions for the ageing population. METHODS: Data from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) harmonized cohort and the English Longitudinal Study of Ageing (ELSA), which is included in ATHLOS, were used. Growth mixture models were implemented to replicate healthy ageing trajectories modelled elsewhere as 'high stable', 'low stable', and 'rapid decline'. Regularized partial correlation networks were used to estimate expected-influence and bridge expected-influence centrality measures. RESULTS: Healthy ageing trajectories modelled with ATHLOS (N = 131116) and ELSA (N = 14904) were consistent with previous work. At the first individual wave, prevalence of problems of respondents in the 'high stable' and 'rapid decline' trajectories were comparable; at the last individual wave, prevalence remained similar for the 'high stable' but increased substantially in all domains for the 'rapid decline' trajectory. Expected-influence centrality measures provided different results than prevalence estimates. For instance, in the first individual wave mobility and carrying, moving, and handling objects had highest impact on overall functioning for the 'rapid decline' and 'high stable' trajectories, while the most prevalent functioning problems concerned cognition, pain, as well as energy and drive functions. CONCLUSIONS: Our study stressed the relevance of healthy ageing trajectories for identifying functioning domains and categories that need to be targeted by rehabilitation services in a heterogeneous ageing population. The use of such trajectories at country level has the potential to make a meaningful contribution to the planning and delivery of rehabilitation interventions through health systems and to informed policy making.

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression.

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

Expression and secretion of SPARC, FGF-21 and DCN in bovine muscle cells: Effects of age and differentiation.

Skeletal muscle growth is an economically important trait in the cattle industry. Secreted muscle-derived proteins, referred to as myokines, have important roles in regulating the growth, metabolism, and health of skeletal muscle in human and biomedical research models. Accumulating evidence supports the importance of myokines in skeletal muscle and whole-body health, though little is known about the potential presence and functional significance of these proteins in cattle. This study evaluates and confirms that secreted proteins acidic and rich in cysteine (SPARC), fibroblast growth factor 21 (FGF-21), myostatin (MSTN), and decorin (DCN) are expressed and SPARC, FGF-21, and DCN are secreted by primary bovine satellite cells from 3- (BSC3; n = 3) and 11- (BSC11; n = 3) month -old commercial angus steers. Cells were cultured and collected at zero, 12, 24, and 48 hours to characterize temporal expression and secretion from undifferentiated and differentiated cells. The expression of SPARC was higher in the undifferentiated (p = 0.04) and differentiated (p = 0.07) BSC11 than BSC3. The same was observed with protein secretion from undifferentiated (p <0.0001) BSC11 compared to BSC3. Protein secretion of FGF-21 was higher in undifferentiated BSC11 (p < 0.0001) vs. BSC3. DCN expression was higher in differentiated BSC11 (p = 0.006) vs. BSC3. Comparing undifferentiated vs. differentiated BSC, MSTN expression was higher in differentiated BSC3 (p ≤ 0.001) for 0, 12, and 24 hours and in BSC11 (p ≤ 0.03) for 0, 12, 24, and 48 hours. There is also a change over time for SPARC expression (p ≤ 0.03) in undifferentiated and differentiated BSC and protein secretion (p < 0.0001) in undifferentiated BSC, as well as FGF-21 expression (p = 0.007) in differentiated BSC. This study confirms SPARC, FGF-21, and DCN are secreted, and SPARC, FGF-21, MSTN, and DCN are expressed in primary bovine muscle cells with age and temporal differences.

Changes in the Proteome of the Circle of Willis during Aging Reveal Signatures of Vascular Disease.

Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of arteries at the base of the brain, links the intracerebral arteries to one another to maintain adequate cerebral perfusion. The CoW proteome is affected in cerebrovascular and neurodegenerative diseases, but changes related to aging have not been described. Here, we report on a quantitative proteomics analysis comparing the CoW from five young (2-3-month-old) and five aged male (18-20-month-old) mice using gene ontology (GO) enrichment, ingenuity pathway analysis (IPA), and iPathwayGuide tools. This revealed 242 proteins that were significantly dysregulated with aging, among which 189 were upregulated and 53 downregulated. GO enrichment-based analysis identified blood coagulation as the top biological function that changed with age and integrin binding and extracellular matrix constituents as the top molecular functions. Consistent with these findings, iPathwayGuide-based impact analysis revealed associations between aging and the complement and coagulation, platelet activation, ECM-receptor interaction, and metabolic process pathways. Furthermore, IPA analysis revealed the enrichment of 97 canonical pathways that contribute to inflammatory responses, as well as 59 inflammation-associated upstream regulators including 39 transcription factors and 20 cytokines. Thus, aging-associated changes in the CoW proteome in male mice demonstrate increases in metabolic, thrombotic, and inflammatory processes.

Multispectral label-free in vivo cellular imaging of human retinal pigment epithelium using adaptive optics fluorescence lifetime ophthalmoscopy improves feasibility for low emission analysis and increases sensitivity for detecting changes with age and eccentricity.

Significance: Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) provides a label-free approach to observe functional and molecular changes at cellular scale in vivo. Adding multispectral capabilities improves interpretation of lifetime fluctuations due to individual fluorophores in the retinal pigment epithelium (RPE). Aim: To quantify the cellular-scale changes in autofluorescence with age and eccentricity due to variations in lipofuscin, melanin, and melanolipofuscin in RPE using multispectral AOFLIO. Approach: AOFLIO was performed on six subjects at seven eccentricities. Four imaging channels ( λ ex / λ em ) were used: 473/SSC, 473/LSC, 532/LSC, and 765/NIR. Cells were segmented and the timing signals of each pixel in a cell were combined into a single histogram, which were then used to compute the lifetime and phasor parameters. An ANOVA was performed to investigate eccentricity and spectral effects on each parameter. Results: A repeatability analysis revealed < 11.8 % change in lifetime parameters in repeat visits for 532/LSC. The 765/NIR and 532/LSC had eccentricity and age effects similar to previous reports. The 473/LSC had a change in eccentricity with mean lifetime and a phasor component. Both the 473/LSC and 473/SSC had changes in eccentricity in the short lifetime component and its relative contribution. The 473/SSC had no trend in eccentricity in phasor. The comparison across the four channels showed differences in lifetime and phasor parameters. Conclusions: Multispectral AOFLIO can provide a more comprehensive picture of changes with age and eccentricity. These results indicate that cell segmentation has the potential to allow investigations in low-photon scenarios such as in older or diseased subjects with the co-capture of an NIR channel (such as 765/NIR) with the desired spectral channel. This work represents the first multispectral, cellular-scale fluorescence lifetime comparison in vivo in the human RPE and may be a useful method for tracking diseases.

Ageing with chronic conditions and older persons' experience of social connections: a qualitative descriptive study.

Background Chronic conditions may limit older peoples' social engagement and wellbeing. Reduced social connections can result in loneliness and social isolation. This study aimed to explore the experience of social connection in older people living with chronic conditions, and the factors influencing their social participation. Methods A purposive sample of 19 community-dwelling older Australians (mean age 75.5years) with one or more chronic conditions participated in a qualitative descriptive study. Semi-structured interviews explored participants' perceptions of their social connections and the potential impact of their chronic conditions. Views about the role of general practice in supporting older persons' wellbeing were discussed. Data were analysed inductively using thematic analysis. Results Five themes were identified: (1) the experience of loneliness, (2) managing diminishing social contacts, (3) living with chronic conditions, (4) barriers to social connection, and (5) facilitators of social connection. Participants felt that ageing with chronic conditions contributed to loss of function and independence, which limited social connections, and increased loneliness and social isolation. Barriers to social connections included issues with mobility, transport and forming new networks. Families were a primary support, with continued community engagement and general practice support crucial to staying well and socially connected. Conclusions Understanding older peoples' experiences, and the barriers and facilitators of social connections can guide clinicians' interventions. General practice is a promising intervention point because of its high use by those with chronic conditions to stay well. General practice nurses are well-placed to collaboratively address the barriers older people face in maintaining social connections.

Mendelian randomization study to assess causality between diet and phenotype of aging.

BACKGROUND AND OBJECTIVES: Observational research findings have demonstrated correlations between diet and the process of aging. Nevertheless, there remains uncertainty regarding possible disruption caused by confounding variables. To elucidate the connections between diet and aging, we employed the Mendelian randomization analysis. METHODS AND STUDY DESIGN: The exposure factor was the daily diet, whereas accelerated aging was measured through telomere length, facial aging (FA), frailty index (FI), and senescence-associated secretory phenotypes (SASPs), representing the outcome factors. The primary analysis employed IVW analysis, with additional MR-Egger and Weighted Median analyses conducted to assess the reliability of the findings. Furthermore, we analyzed the heterogeneity and pleiotropy of the results. RESULTS: The results revealed that the consumption of salad/raw vegetables and oily fish exhibited a negative correlation with FA, whereas coffee intake showed a positive correlation with FA. On the other hand, the intake of cheese, oily fish, dried fruit, and cereal showed negative associations with FI. Additionally, coffee, alcohol, and pork intake were positively associated with FI. Lastly, the intake of bread exhibited a positively correlated with SASPs, while the intake of cheese and coffee showed a negative correlation with SASPs. CONCLUSIONS: Our study revealed that the consumption of cheese, vegetables, oily fish, dried fruit, bread, coffee, and alcohol was associated with the aging process. Interestingly, our findings suggest that coffee intake may accelerate aging, whereas intake of oily fish may delay the aging process. However, it is important to note that further well-designed prospective studies are required to validate our findings in the future.

Evaluating age-and gender-related changes in brain volumes in normal adult using synthetic magnetic resonance imaging.

OBJECTIVE: Normal aging is associated with brain volume change, and brain segmentation can be performed within an acceptable scan time using synthetic magnetic resonance imaging (MRI). This study aimed to investigate the brain volume changes in healthy adult according to age and gender, and provide age- and gender-specific reference values using synthetic MRI. METHODS: A total of 300 healthy adults (141 males, median age 48; 159 females, median age 50) were underwent synthetic MRI on 3.0 T. Brain parenchymal volume (BPV), gray matter volume (GMV), white matter volume (WMV), myelin volume (MYV), and cerebrospinal fluid volume (CSFV) were calculated using synthetic MRI software. These volumes were normalized by intracranial volume to normalized GMV (nGMV), normalized WMV (nWMV), normalized MYV (nMYV), normalized BPV (nBPV), and normalized CSFV (nCSFV). The normalized brain volumes were plotted against age in both males and females, and a curve fitting model that best explained the age dependence of brain volume was identified. The normalized brain volumes were compared between different age and gender groups. RESULTS: The approximate curves of nGMV, nWMV, nCSFV, nBPV, and nMYV were best fitted by quadratic curves. The nBPV decreased monotonously through all ages in both males and females, while the changes of nCSFV showed the opposite trend. The nWMV and nMYV in both males and females increased gradually and then decrease with age. In early adulthood (20s), nWMV and nMYV in males were lower and peaked later than that in females (p < .005). The nGMV in both males and females decreased in the early adulthood until the 30s and then remains stable. A significant decline in nWMV, nBPV, and nMYV was noted in the 60s (Turkey test, p < .05). CONCLUSIONS: Our study provides age- and gender-specific reference values of brain volumes using synthetic MRI, which could be objective tools for discriminating brain disorders from healthy brains.

Correlation between obesity and early vascular aging in middle-aged and young adult health check-up populations. / ä¸­é’å¹´å¥åº·ä½“æ£€äººç¾¤è‚¥èƒ–ä¸Žæ—©å‘è¡€ç®¡è€åŒ–çš„ç›¸å ³æ€§.

OBJECTIVES: The obesity rate among middle-aged and young adults in China is increasing annually, and the incidence of cardiovascular diseases is becoming more prevalent in younger populations. However, it has not yet been reported whether obesity is associated with early vascular aging (EVA). This study aims to explore the correlation between obesity and EVA in middle-aged and young adult health check-up populations, providing a reference for the prevention of cardiovascular diseases. METHODS: A total of 15 464 middle-aged and young adults aged 18-59 who completed brachial-ankle pulse wave velocity (baPWV) test in the Third Xiangya Hospital of Central South University from January to December 2020 were included. Among them, 1 965 individuals with normal blood pressure and no cardiovascular risk factors were selected as the healthy population. The baPWV thresholds for determining EVA in each age group for males and females were calculated based on the baPWV values of the healthy population. The number and percentage of individuals meeting the EVA criteria in the middle-aged and young adult health check-up populations were statistically analyzed by age and gender. The differences in obesity indicators [visceral adiposity index (VAI), body mass index (BMI), waist circumference (WC)] between the EVA and non-EVA groups for males and females were compared. Using EVA as the dependent variable, VAI, BMI, and WC were included as independent variables in a Logistic model to analyze the correlation between each obesity indicator and EVA before and after adjusting for other influencing factors. Furthermore, the correlation between each obesity indicator and EVA in each age group was analyzed. RESULTS: In the health check-up populations, the detection rate of EVA in different age groups was 1.65%-10.92% for males, and 1.16%-10.50% for females, the detection rate of EVA increased with age in both males and females. Except for the 40-<50 age group, the EVA detection rate was higher in males than in females in all other age groups. Regardless of gender, obesity indicators VAI, BMI, and WC were significantly higher in the EVA group than in the non-EVA group (all P<0.01). Before and after adjusting for other influencing factors, VAI and WC were both correlated with EVA (both P<0.05). BMI was a risk factor for EVA before adjusting for other influencing factors (P<0.01), but after adjustment, the correlation between BMI and EVA was not statistically significant (P=0.05). After adjusting for other influencing factors, the correlation between VAI and EVA was statistically significant in the 18-<40 and 50-<60 age groups (both P<0.05), while the correlation between BMI and WC with EVA was not statistically significant (both P>0.05). In the 40-<50 age group, the correlation between VAI and BMI with EVA was not statistically significant (both P>0.05), but the correlation between WC and EVA was statistically significant (P<0.01). CONCLUSIONS: VAI is closely related to the occurrence of EVA in middle-aged and young adults aged 18-<40 and 50-<60 years, while WC is closely related to the occurrence of EVA in those aged 40-<50 years.

The use of natural language processing for the identification of ageing syndromes including sarcopenia, frailty and falls in electronic healthcare records: a systematic review.

BACKGROUND: Recording and coding of ageing syndromes in hospital records is known to be suboptimal. Natural Language Processing algorithms may be useful to identify diagnoses in electronic healthcare records to improve the recording and coding of these ageing syndromes, but the feasibility and diagnostic accuracy of such algorithms are unclear. METHODS: We conducted a systematic review according to a predefined protocol and in line with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Searches were run from the inception of each database to the end of September 2023 in PubMed, Medline, Embase, CINAHL, ACM digital library, IEEE Xplore and Scopus. Eligible studies were identified via independent review of search results by two coauthors and data extracted from each study to identify the computational method, source of text, testing strategy and performance metrics. Data were synthesised narratively by ageing syndrome and computational method in line with the Studies Without Meta-analysis guidelines. RESULTS: From 1030 titles screened, 22 studies were eligible for inclusion. One study focussed on identifying sarcopenia, one frailty, twelve falls, five delirium, five dementia and four incontinence. Sensitivity (57.1%-100%) of algorithms compared with a reference standard was reported in 20 studies, and specificity (84.0%-100%) was reported in only 12 studies. Study design quality was variable with results relevant to diagnostic accuracy not always reported, and few studies undertaking external validation of algorithms. CONCLUSIONS: Current evidence suggests that Natural Language Processing algorithms can identify ageing syndromes in electronic health records. However, algorithms require testing in rigorously designed diagnostic accuracy studies with appropriate metrics reported.

Age-related changes in cheek skin movement: A case study of Japanese women.

BACKGROUND: The majority of conventional studies on skin aging have focused on static conditions. However, in daily life, the facial skin we encounter is constantly in motion due to conversational expressions and changes in facial expressions, causing the skin to alter its position and shape, resulting in a dynamic state. Consequently, it is hypothesized that characteristics of aging not apparent in static conditions may be present in the dynamic state of the skin. Therefore, this study investigates age-related changes in dynamic skin characteristics associated with facial expression alterations. METHODS: A motion capture system measured the dynamic characteristics (delay and stretchiness of skin movement associated with expression) of the cheek skin in response to facial expressions among 86 Japanese women aged between 20 and 69 years. RESULTS: The findings revealed an increase in the delay of cheek skin response to facial expressions (r = 0.24, p < 0.05) and a decrease in the stretchiness of the lower cheek area with age (r = 0.60, p < 0.01). An increasing variance in delay and stretchiness within the same age group was also observed with aging. CONCLUSION: The findings of this study revealed that skin aging encompasses both static characteristics, such as spots, wrinkles, and sagging, traditionally studied in aging research, and dynamic aging characteristics of the skin that emerge in response to facial expression changes. These dynamic aging characteristics could pave the way for the development of new methodologies in skin aging analysis and potentially improve our understanding and treatment of aging impressions that are visually perceptible in daily life but remain unexplored.

[Mechanisms of the Effect of Maternal Age-Related Oocyte Aging on Fertility: Transcriptomic Sequencing Analysis of a Zebrafish Model]. / æ¯ä½“å¹´é¾„ç›¸å ³çš„åµæ¯ç»†èƒžè€åŒ–å¯¹ç”Ÿè‚²åŠ›çš„å½±å“æœºåˆ¶ï¼šæ–‘é©¬é±¼æ¨¡åž‹çš„è½¬å½•ç»„å­¦æµ‹åºåˆ†æž.

Objective: Female fertility gradually decreases with the increase in women's age. The underlying reasons include the decline in the quantity and quality of oocytes. Oocyte aging is an important manifestation of the decline in oocyte quality, including in vivo oocyte aging before ovulation and in vitro oocyte aging after ovulation. Currently, few studies have been done to examine oocyte aging, and the relevant molecular mechanisms are not fully understood. Therefore, we used zebrafish as a model to investigate oocyte aging. Three different age ranges of female zebrafish were selected to mate with male zebrafish of the best breeding age. In this way, we studied the effects of maternal age-related oocyte aging on fertility and investigated the potential molecular mechanisms behind maternal age-related fertility decline. Methods: Eight female zebrafish aged between 158 and 195 d were randomly selected for the 6-month age group (180±12) d, 8 female zebrafish aged between 330 and 395 d were randomly selected for the 12-month age group (360±22) d, and 8 female zebrafish aged between 502 and 583 d were randomly selected for the 18-month age group (540±26) d. Male zebrafish of (180±29) d were randomly selected from zebrafish aged between 158 and 195 d and mated with female zebrafish in each group. Each mating experiment included 1 female zebrafish and 1 male zebrafish. Zebrafish embryos produced by the mating experiments were collected and counted. The embryos at 4 hours post-fertilization were observed under the microscope, the total number of embryos and the number of unfertilized embryos were counted, and the fertilization rate was calculated accordingly. The numbers of malformed embryos and dead embryos were counted 24 hours after fertilization, and the rates of embryo malformation and mortality were calculated accordingly. The primary outcome measure was the embryo fertilization rate, and the secondary outcome measures were the number of embryos per spawn (the total number of embryos laid within 1.5 hours after the beginning of mating and reproduction of the zebrafish), embryo mortality, and embryo malformation rate. The outcome measures of each group were compared. The blastocyst embryos of female zebrafish from each group born after mating with male zebrafish in their best breeding period were collected for transcriptomics analysis. Fresh oocytes of female zebrafish in each group were collected for transcriptomics analysis to explore the potential molecular mechanisms of maternal age-related fertility decline. Results: Compared with that of the 6-month group (94.9%±3.6%), the embryo fertilization rate of the 12-month group (92.3%±4.2%) showed no significant difference, but that of the 18-month group (86.8%±5.5%) decreased significantly (P<0.01). In addition, the fertilization rate in the 18-month group was significantly lower than that in the 12-month group (P<0.05). Compared with that of the 6-month group, the embryo mortality of the female zebrafish in the 12-month group and that in the 18-month group were significantly higher than that in the 6-month group (P<0.000 1, P<0.001). There was no significant difference in the number of embryos per spawn or in the embryo malformation rate among the three groups. The results of the transcriptomics analysis of blastocyst embryos showed that some genes, including dusp5, bdnf, ppip5k2, dgkg, aldh3a2a, acsl1a, hal, mao, etc, were differentially expressed in the 12-month group or the 18-month group compared with their expression levels in the 6-month group. According to the KEGG enrichment analysis, these differentially expressed genes (DEGs) were significantly enriched in the MAPK signaling pathway, the phosphatidylinositol signaling system, and the fatty acid degradation and histidine metabolism pathway (P<0.05). The analysis of the expression trends of the genes expressed differentially among the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that the gene expression trends of fancc, fancg, fancb, and telo2, which were involved in Fanconi anemia pathway, were statistically significant (P<0.05). In the results of oocyte transcriptomics analysis, the genes that were differentially expressed in the 12-month group or the 18-month group compared with the 6-month group were mainly enriched in cell adhesion molecules and the protein digestion and absorption pathway (P<0.05). The results of the trends of gene expression in the zebrafish oocytes of the three groups (the 6-month group, the 12-month group, and the 18-month group in turn) showed that three kinds of gene expression trends of declining fertility with growing maternal age had significant differences (P<0.05). Further analysis of the three significantly differential expression trends showed 51 DEGs related to mitochondria and 5 DEGs related to telomere maintenance and DNA repair, including tomm40, mpc2, nbn, tti1, etc. Conclusion: With the increase in the maternal age of the zebrafish, the embryo fertilization rate decreased significantly and the embryo mortality increased significantly. In addition, with the increase in the maternal age of the zebrafish, the expression of mitochondria and telomere-related genes, such as tomm40, mpc2, nbn, and tti1, in female zebrafish oocytes decreased gradually. Maternal age may be a factor contributing to the decrease in oocyte fertilization ability and the increase in early embryo mortality. Maternal age-related oocyte aging affects the fertility and embryo development of the offspring.

Long-term culture of patient-derived mammary organoids in non-biogenic electrospun scaffolds for identifying metalloprotein and motor protein activities in aging and senescence.

We recently identified TMEM230 as a master regulator of the endomembrane system of cells. TMEM230 expression is necessary for promoting motor protein dependent intracellular trafficking of metalloproteins for cellular energy production in mitochondria. TMEM230 is also required for transport and secretion of metalloproteinases for autophagy and phagosome dependent clearance of misfolded proteins, defective RNAs and damaged cells, activities that decline with aging. This suggests that aberrant levels of TMEM230 may contribute to aging and regain of proper levels may have therapeutic applications. The components of the endomembrane system include the Golgi complex, other membrane bound organelles, and secreted vesicles and factors. Secreted cellular components modulate immune response and tissue regeneration in aging. Upregulation of intracellular packaging, trafficking and secretion of endosome components while necessary for tissue homeostasis and normal wound healing, also promote secretion of pro-inflammatory and pro-senescence factors. We recently determined that TMEM230 is co-regulated with trafficked cargo of the endomembrane system, including lysosome factors such as RNASET2. Normal tissue regeneration (in aging), repair (following injury) and aberrant destructive tissue remodeling (in cancer or autoimmunity) likely are regulated by TMEM230 activities of the endomembrane system, mitochondria and autophagosomes. The role of TMEM230 in aging is supported by its ability to regulate the pro-inflammatory secretome and senescence-associated secretory phenotype in tissue cells of patients with advanced age and chronic disease. Identifying secreted factors regulated by TMEM230 in young patients and patients of advanced age will facilitate identification of aging associated targets that aberrantly promote, inhibit or reverse aging. Ex situ culture of patient derived cells for identifying secreted factors in tissue regeneration and aging provides opportunities in developing therapeutic and personalized medicine strategies. Identification and validation of human secreted factors in tissue regeneration requires long-term stabile scaffold culture conditions that are different from those previously reported for cell lines used as cell models for aging. We describe a 3 dimensional (3D) platform utilizing non-biogenic and non-labile poly ε-caprolactone scaffolds that supports maintenance of long-term continuous cultures of human stem cells, in vitro generated 3D organoids and patient derived tissue. Combined with animal component free culture media, non-biogenic scaffolds are suitable for proteomic and glycobiological analyses to identify human factors in aging. Applications of electrospun nanofiber technologies in 3D cell culture allow for ex situ screening and the development of patient personalized therapeutic strategies and predicting their effectiveness in mitigating or promoting aging.

[The relationship between intraocular pressure and age-related variations in ocular rigidity]. / Vzaimosvyaz' vnutriglaznogo davleniya s involyutsionnymi kolebaniyami rigidnosti glaza.

PURPOSE: This study aimed to identify the correlation between age-related fluctuations in the average values of rigidity of the fibrous tunic of the eye (FTE) and corresponding ranges of true intraocular pressure (IOP) in healthy eyes and eyes with open-angle glaucoma (OAG); using the identified ranges of FTE rigidity, to establish the appropriate IOP zones for healthy and glaucomatous eyes, taking into account the aging periods as classified by the World Health Organization (WHO). MATERIAL AND METHODS: Ocular-Response Analyzer tonometry was used according to the Koshits-Svetlova dynamic diagnostic method to examine 674 patients with healthy eyes and 518 patients with glaucomatous eyes, aged 18 to 90 years, classified according to the WHO aging periods, and a theoretical analysis was conducted to estimate clinical values of FTE rigidity, the current level of true IOP, and the calculated individual IOP level in a patient's eye during youth. RESULTS: The following IOP level zones were identified for patients with healthy and glaucomatous eyes: low IOP zone (≤13 mm Hg); medium IOP zone (14-20 mm Hg); elevated IOP zone (21-26 mm Hg); high IOP zone (27-32 mm Hg); subcompensated IOP zone (33-39 mm Hg); and decompensated IOP zone (≥40 mm Hg). CONCLUSION: The fundamental physiological criterion "rigidity" does not depend on central corneal thickness and consistently reflects the current level of true IOP. In all examined patients, both with healthy and glaucomatous eyes, healthy and glaucoma eyes with the same level of current rigidity had the same level of IOP. The ability to assign a given healthy or glaucomatous eye to a specific individual IOP zone is particularly important for the polyclinic system.