The global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic ...diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of well‐established clinical guidelines. Physicians are often forced to engage in cycles of “trial and error” that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are “aging faster” to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine.
Finding a reference metric for the rate of biological aging is key to understanding the molecular nature of the aging process. Defining and validating this metric in humans opens the door to a new kind of medicine that will overcome the limitation of current disease definitions. We will then be able to approach health in a global perspective and bring life course preventative measures to the center of attention.
The most promising way to prevent the explosive spread of COVID-19 infection is to achieve herd immunity through vaccination. It is therefore important to motivate those who are less willing to be ...vaccinated. To address this issue, we conducted an online survey of 6232 Japanese people to investigate age- and gender-dependent differences in attitudes towards COVID-19 vaccination and the underlying psychological processes. We asked participants to read one of nine different messages about COVID-19 vaccination and rate their willingness to be vaccinated. We also collected their 17 social personality trait scores and demographic information. We found that males 10-20 years old were least willing to be vaccinated. We also found that prosocial traits are the driving force for young people, but the motivation in older people also depends on risk aversion and self-interest. Furthermore, an analysis of 9 different messages demonstrated that for young people (particularly males), the message emphasizing the majority's intention to vaccinate and scientific evidence for the safety of the vaccination had the strongest positive effect on the willingness to be vaccinated, suggesting that the "majority + scientific evidence" message nudges young people to show their prosocial nature in action.
Guilt aversion, which describes the tendency to reduce the discrepancy between a partner's expectation and his/her actual outcome, is a key driving force for cooperation in both the East and West. A ...recent study based on functional magnetic resonance imaging and online behavioral experiments reported that men show stronger guilt aversion than women and also suggested that men's predominance in guilt aversion arises from stronger sensitivity to social norms. However, since the participants of that study were all Japanese, it remains unaddressed how common the gender difference in guilt aversion is. Here, we conducted online behavioral studies on people from Korea and the UK (Korea; n = 294, UK; n = 347) using the same trust game. We confirmed that men exhibit stronger guilt aversion than women in both countries. Furthermore, consistent with the Japanese study, our Lasso regression analysis for UK participants revealed that Big Five Conscientiousness (rule-based decision) correlated with guilt aversion in men. In contrast, guilt aversion in Korean men correlated with Big Five Neuroticism. Thus, our results suggest that gender differences in guilt aversion are universal but the underlying cognitive processes may be influenced by cultural differences.
The initial decrease in the blood oxygenation level-dependent (BOLD) signal reflects primary neuronal activity more than the later hemodynamic positive peak responses. Moreover, ultra-high field BOLD ...has high sensitivity for the initial de-oxygenation signal. However, it is not fully understood how much information about task events and cognitive processes the initial decrease in the BOLD signal contains. Multivoxel pattern analysis (MVPA) of the BOLD signal has enabled the quantification of information contained in the activity patterns, but it has mainly relied on the positive peak responses. Here, we applied a signal-based functional inter-individual alignment algorithm (i.e., hyper-alignment) to a 7T-BOLD timeseries scanned while participants conducted a facial expression discrimination task. We found that the MVPA decoding accuracy in the bilateral amygdala 2 s after the face onset was significantly beyond chance. Furthermore, we confirmed that the voxels contributing to the decoding accuracy at 2 s displayed a decreasing hemodynamics response. These results demonstrated that the initial decrease in 7T-BOLD signals contains finer information about task events and cognitive processes than thought previously.
To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and ...women, 22–93 years old, who were disease‐ and treatment‐free and had no physical and cognitive impairment. Using a p ≤ 3.83 × 10−5 significance threshold, 197 proteins were positively associated, and 20 proteins were negatively associated with age. Growth differentiation factor 15 (GDF15) had the strongest, positive association with age (GDF15; 0.018 ± 0.001, p = 7.49 × 10−56). In our sample, GDF15 was not associated with other cardiovascular risk factors such as cholesterol or inflammatory markers. The functional pathways enriched in the 217 age‐associated proteins included blood coagulation, chemokine and inflammatory pathways, axon guidance, peptidase activity, and apoptosis. Using elastic net regression models, we created a proteomic signature of age based on relative concentrations of 76 proteins that highly correlated with chronological age (r = 0.94). The generalizability of our findings needs replication in an independent cohort.
Comparing transcript levels between healthy and diseased individuals allows the identification of differentially expressed genes, which may be causes, consequences or mere correlates of the disease ...under scrutiny. We propose a method to decompose the observational correlation between gene expression and phenotypes driven by confounders, forward- and reverse causal effects. The bi-directional causal effects between gene expression and complex traits are obtained by Mendelian Randomization integrating summary-level data from GWAS and whole-blood eQTLs. Applying this approach to complex traits reveals that forward effects have negligible contribution. For example, BMI- and triglycerides-gene expression correlation coefficients robustly correlate with trait-to-expression causal effects (r
= 0.11, P
= 2.0 × 10
and r
= 0.13, P
= 1.1 × 10
), but not detectably with expression-to-trait effects. Our results demonstrate that studies comparing the transcriptome of diseased and healthy subjects are more prone to reveal disease-induced gene expression changes rather than disease causing ones.
SomaScan is a high-throughput, aptamer-based proteomics assay designed for the simultaneous measurement of thousands of proteins with a broad range of endogenous concentrations. In its most current ...version, the 7k SomaScan assay v4.1 is capable of measuring 7288 human proteins. In this work, we present an extensive technical assessment of this platform based on a study of 2050 samples across 22 plates. Included in the study design were inter-plate technical duplicates from 102 human subjects, which allowed us to characterize different normalization procedures, evaluate assay variability by multiple analytical approaches, present signal-over-background metrics, and discuss potential specificity issues. By providing detailed performance assessments on this wide range of technical aspects, we aim for this work to serve as a valuable resource for the growing community of SomaScan users.
Flavones, which are distributed in a variety of plants and foods in nature, possess significant biological activities, including antitumor and anti-inflammatory effects, and are metabolized into ...glucuronides by uridine 5′-diphosphate (UDP)-glucuronosyltransferase (UGT) enzymes in humans. In this study, apigenin, acacetin, and genkwanin, flavones having hydroxyl groups at C5, C7, and/or C4′positions were focused on, and the regioselective glucuronidation in human liver and intestinal microsomes was examined. Two glucuronides (namely, AP-7G and AP-4′G for apigenin, AC-5G and AC-7G for acacetin, and GE-5G and GE-4′G for genkwanin) were formed from each flavone by liver and intestinal microsomes, except for only GE-4′G formation from genkwanin by intestinal microsomes. The order of total glucuronidation activities was liver microsomes > intestinal microsomes for apigenin and acacetin, and liver microsomes < intestinal microsomes for genkwanin. The order of CLint values (x-intercept) based on v versus V/S plots for apigenin glucuronidation was AP-7G > AP-4′G in liver microsomes and AP-7G < AP-4′G in intestinal microsomes. The order of CLint values was AC-5G < AC-7G for acacetin and GE-5G < GE-4′G genkwanin glucuronidation in both liver and intestinal microsomes. This suggests that the abilities and roles of UGT enzymes in the glucuronidation of apigenin, acacetin, and genkwanin in humans differ depending on the chemical structure of flavones.
Behavioral and lifestyle factors have been shown to relate to a number of health-related outcomes, yet there is a need for studies that examine their relationship to molecular aging rates. Toward ...this end, we use recent epigenetic biomarkers of age that have previously been shown to predict all-cause mortality, chronic conditions, and age-related functional decline. We analyze cross-sectional data from 4,173 postmenopausal female participants from the Women's Health Initiative, as well as 402 male and female participants from the Italian cohort study, Invecchiare nel Chianti.Extrinsic epigenetic age acceleration (EEAA) exhibits significant associations with fish intake (p=0.02), moderate alcohol consumption (p=0.01), education (p=3x10
), BMI (p=0.01), and blood carotenoid levels (p=1x10
)-an indicator of fruit and vegetable consumption, whereas intrinsic epigenetic age acceleration (IEAA) is associated with poultry intake (p=0.03) and BMI (p=0.05). Both EEAA and IEAA were also found to relate to indicators of metabolic syndrome, which appear to mediate their associations with BMI. Metformin-the first-line medication for the treatment of type 2 diabetes-does not delay epigenetic aging in this observational study. Finally, longitudinal data suggests that an increase in BMI is associated with increase in both EEAA and IEAA.Overall, the epigenetic age analysis of blood confirms the conventional wisdom regarding the benefits of eating a high plant diet with lean meats, moderate alcohol consumption, physical activity, and education, as well as the health risks of obesity and metabolic syndrome.
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