Predicting successful ageing among older adults seems possible even as far as two decades ahead.

BACKGROUND: Successful ageing is the term often used for depicting exceptional ageing and can be measured with multidimensional models including physical, psychological and social wellbeing. The aim of this study was to test multidimensional successful ageing models to investigate whether these models can predict successful ageing, and which individual subcomponents included in the models are most significantly associated with successful ageing. METHODS: Successful ageing was defined as the ability to live at home without daily care at the age of 84 years or over. Data on the participants' physical, psychological and social wellbeing were gathered at baseline and the follow-up period was 20 years. Four successful ageing models were constructed. Backward stepwise logistic regression analysis was used to identify the individual subcomponents of the models which best predicted successful ageing. RESULTS: All successful ageing models were able to predict ageing successfully after the 20-year follow-up period. After the backward stepwise logistic regression analysis, three individual subcomponents of four models remained statistically significant and were included in the new model: having no heart disease, having good self-rated health and feeling useful. As a model, using only these three subcomponents, the association with successful ageing was similar to using the full models. CONCLUSIONS: Multidimensional successful ageing models were able to predict successful ageing after a 20-year follow-up period. However, according to the backward stepwise logistic regression analysis, the three subcomponents (absence of heart disease, good self-rated health and feeling useful) significantly associated with successful ageing performed as well as the multidimensional successful ageing models in predicting ageing successfully.

Dental pulp stem cells ameliorate D-galactose-induced cardiac ageing in rats.

Background: Ageing is a key risk factor for cardiovascular disease and is linked to several alterations in cardiac structure and function, including left ventricular hypertrophy and increased cardiomyocyte volume, as well as a decline in the number of cardiomyocytes and ventricular dysfunction, emphasizing the pathological impacts of cardiomyocyte ageing. Dental pulp stem cells (DPSCs) are promising as a cellular therapeutic source due to their minimally invasive surgical approach and remarkable proliferative ability. Aim: This study is the first to investigate the outcomes of the systemic transplantation of DPSCs in a D-galactose (D-gal)-induced rat model of cardiac ageing. Methods. Thirty 9-week-old Sprague-Dawley male rats were randomly assigned into three groups: control, ageing (D-gal), and transplanted groups (D-gal + DPSCs). D-gal (300 mg/kg/day) was administered intraperitoneally daily for 8 weeks. The rats in the transplantation group were intravenously injected with DPSCs at a dose of 1 × 106 once every 2 weeks. Results: The transplanted cells migrated to the heart, differentiated into cardiomyocytes, improved cardiac function, upregulated Sirt1 expression, exerted antioxidative effects, modulated connexin-43 expression, attenuated cardiac histopathological alterations, and had anti-senescent and anti-apoptotic effects. Conclusion: Our results reveal the beneficial effects of DPSC transplantation in a cardiac ageing rat model, suggesting their potential as a viable cell therapy for ageing hearts.

A murine model of hypertensive heart disease in older women.

We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension from Angiotensin II infusion (AngII), menopause, and advanced age. To mimic menopause, we delayed ovariectomy (Ovx) at 12 months of age. We also studied the effects of AngII infusion for 28 days in younger animals and the impact of losing gonadal steroids earlier in life. We observed that AngII effects on heart morphology were different in younger and adult mice (3- and 12-month-old; 20 and 19% increase in heart weight. P < 0.01 for both) than in older animals (24-month-old; 6%; not significant). Ovariectomy at 12 months restored the hypertrophic response to AngII in elderly females (23%, p = 0.0001). We performed a bulk RNA sequencing study of the left ventricle (LV) and left atrial gene expression in elderly animals, controls, and Ovx. AngII modulated (|Log2 fold change| ≥ 1) the LV expression of 170 genes in control females and 179 in Ovx ones, 64 being shared. In the left atrium, AngII modulated 235 genes in control females and 453 in Ovx, 140 shared. We observed many upregulated genes associated with the extracellular matrix regulation in both heart chambers. Many of these upregulated genes were shared between the ventricle and the atrium as well as in control and Ovx animals, namely for the most expressed Ankrd1, Nppb, Col3a1, Col1a1, Ctgf Col8a1, and Cilp. Several circadian clock LV genes were modulated differently by AngII between control and Ovx females (Clock, Arntl, Per2, Cry2, and Ciart). In conclusion, sex hormones, even in elderly female mice, modulate the heart's hypertrophic response to AngII. Our study identifies potential new markers of hypertensive disease in aging female mice and possible disturbances of their cardiac circadian clock.

Identification of factors associated with sarcopenic obesity development: Literature review and expert panel voting.

Sarcopenic obesity (SO) is defined as the combination of excess fat mass (obesity) and low skeletal muscle mass and function (sarcopenia). The identification and classification of factors related to SO would favor better prevention and diagnosis. The present article aimed to (i) define a list of factors related with SO based on literature analysis, (ii) identify clinical conditions linked with SO development from literature search and (iii) evaluate their relevance and the potential research gaps by consulting an expert panel. From 4746 articles screened, 240 articles were selected for extraction of the factors associated with SO. Factors were classified according to their frequency in the literature. Clinical conditions were also recorded. Then, they were evaluated by a panel of expert for evaluation of their relevance in SO development. Experts also suggested additional factors. Thirty-nine unique factors were extracted from the papers and additional eleven factors suggested by a panel of experts in the SO field. The frequency in the literature showed insulin resistance, dyslipidemia, lack of exercise training, inflammation and hypertension as the most frequent factors associated with SO whereas experts ranked low spontaneous physical activity, protein and energy intakes, low exercise training and aging as the most important. Although literature and expert panel presented some differences, this first list of associated factors could help to identify patients at risk of SO. Further work is needed to confirm the contribution of factors associated with SO among the population overtime or in randomized controlled trials to demonstrate causality.

Psychogenic Aging: A Novel Prospect to Integrate Psychobiological Hallmarks of Aging.

Psychological factors are amongst the most robust predictors of healthspan and longevity, yet are rarely incorporated into scientific and medical frameworks of aging. The prospect of characterizing and integrating the psychological influences of aging is therefore an unmet step for the advancement of geroscience. Psychogenic Aging research is an emerging branch of biogerontology that aims to address this gap by investigating the impact of psychological factors on human longevity. It is an interdisciplinary field that integrates complex psychological, neurological, and molecular relationships that can be best understood with precision medicine methodologies. This perspective argues that psychogenic aging should be considered an integral component of the Hallmarks of Aging framework, opening the doors for future biopsychosocial integration in longevity research. By providing a unique perspective on frequently overlooked aspects of organismal aging, psychogenic aging offers new insights and targets for anti-aging therapeutics on individual and societal levels that can significantly benefit the scientific and medical communities.

Role of epigenetic regulatory mechanisms in age-related bone homeostasis imbalance.

Alterations to the human organism that are brought about by aging are comprehensive and detrimental. Of these, an imbalance in bone homeostasis is a major outward manifestation of aging. In older adults, the decreased osteogenic activity of bone marrow mesenchymal stem cells and the inhibition of bone marrow mesenchymal stem cell differentiation lead to decreased bone mass, increased risk of fracture, and impaired bone injury healing. In the past decades, numerous studies have reported the epigenetic alterations that occur during aging, such as decreased core histones, altered DNA methylation patterns, and abnormalities in noncoding RNAs, which ultimately lead to genomic abnormalities and affect the expression of downstream signaling osteoporosis treatment and promoter of fracture healing in older adults. The current review summarizes the impact of epigenetic regulation mechanisms on age-related bone homeostasis imbalance.

Effects of age and noise exposure history on auditory nerve response amplitudes: A systematic review, study, and meta-analysis.

Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r = -0.407), but noise exposure effects are weak (r = -0.152). We conclude that noise exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.

The role of cognitive flexibility on higher level executive functions in mild cognitive impairment and healthy older adults.

BACKGROUND: Mild Cognitive Impairment (MCI) is a preclinical condition between healthy and pathological aging, which is characterized by impairments in executive functions (EFs), including cognitive flexibility. According to Diamond's model, cognitive flexibility is a core executive function, along with working memory and inhibition, but it requires the development of these last EFs to reach its full potential. In this model, planning and fluid intelligence are considered higher-level EFs. Given their central role in enabling individuals to adapt their daily life behavior efficiently, the goal is to gain valuable insight into the functionality of cognitive flexibility in a preclinical form of cognitive decline. This study aims to investigate the role of cognitive flexibility and its components, set-shifting and switching, in MCI. The hypotheses are as follows: (I) healthy participants are expected to perform better than those with MCI on cognitive flexibility and higher-level EFs tasks, taking into account the mediating role of global cognitive functioning; (II) cognitive flexibility can predict performance on higher-level EFs (i.e., planning and fluid intelligence) tasks differently in healthy individuals and those diagnosed with MCI. METHODS: Ninety participants were selected and divided into a healthy control group (N = 45; mean age 64.1 ± 6.80; 66.6% female) and an MCI group (N = 45; mean age 65.2 ± 8.14; 40% female). Cognitive flexibility, fluid intelligence, planning, and global cognitive functioning of all participants were assessed using standardized tasks. RESULTS: Results indicated that individuals with MCI showed greater impairment in global cognitive functioning and EFs performance. Furthermore, the study confirms the predictive role of cognitive flexibility for higher EFs in individuals with MCI and only partially in healthy older adults.

Addressing the Missing Links in Cardiovascular Aging.

The aim of this manuscript is to provide a review of available options to enhance cardiovascular health and prevent cardiovascular disease (CVD) in the aging population using a systems-biology approach. These include the role of the gut microbiome, the early identification and removal of environmental toxins, and finally age related sex hormones and supplement replacement which all influence aging. Implementing such a comprehensive approach has the potential to facilitate earlier risk assessment, disease prevention, and even improve mortality. Further study in these areas will continue to advance our understanding and refine therapeutic interventions for a healthier cardiovascular aging process.

Sex Differences in Aging-related Myocardial Stiffening Quantitatively Measured with MR Elastography.

Purpose To investigate the feasibility of using quantitative MR elastography (MRE) to characterize the influence of aging and sex on left ventricular (LV) shear stiffness. Materials and Methods In this prospective study, LV myocardial shear stiffness was measured in 109 healthy volunteers (age range: 18-84 years; mean age, 40 years ± 18 [SD]; 57 women, 52 men) enrolled between November 2018 and September 2019, using a 5-minute MRE acquisition added to a clinical MRI protocol. Linear regression models were used to estimate the association of cardiac MRI and MRE characteristics with age and sex; models were also fit to assess potential age-sex interaction. Results Myocardial shear stiffness significantly increased with age in female (age slope = 0.03 kPa/year ± 0.01, P = .009) but not male (age slope = 0.008 kPa/year ± 0.009, P = .38) volunteers. LV ejection fraction (LVEF) increased significantly with age in female volunteers (0.23% ± 0.08 per year, P = .005). LV end-systolic volume (LVESV) decreased with age in female volunteers (-0.20 mL/m2 ± 0.07, P = .003). MRI parameters, including T1, strain, and LV mass, did not demonstrate this interaction (P > .05). Myocardial shear stiffness was not significantly correlated with LVEF, LV stroke volume, body mass index, or any MRI strain metrics (P > .05) but showed significant correlations with LV end-diastolic volume/body surface area (BSA) (slope = -3 kPa/mL/m2 ± 1, P = .004, r2 = 0.08) and LVESV/BSA (-1.6 kPa/mL/m2 ± 0.5, P = .003, r2 = 0.08). Conclusion This study demonstrates that female, but not male, individuals experience disproportionate LV stiffening with natural aging, and these changes can be noninvasively measured with MRE. Keywords: Cardiac, Elastography, Biological Effects, Experimental Investigations, Sexual Dimorphisms, MR Elastography, Myocardial Shear Stiffness, Quantitative Stiffness Imaging, Aging Heart, Myocardial Biomechanics, Cardiac MRE Supplemental material is available for this article. Published under a CC BY 4.0 license.

Advancing Tissue Damage Repair in Geriatric Diseases: Prospects of Combining Stem Cell-Derived Exosomes with Hydrogels.

Geriatric diseases are a group of diseases with unique characteristics related to senility. With the rising trend of global aging, senile diseases now mainly include endocrine, cardiovascular, neurodegenerative, skeletal, and muscular diseases and cancer. Compared with younger populations, the structure and function of various cells, tissues and organs in the body of the elderly undergo a decline as they age, rendering them more susceptible to external factors and diseases, leading to serious tissue damage. Tissue damage presents a significant obstacle to the overall health and well-being of older adults, exerting a profound impact on their quality of life. Moreover, this phenomenon places an immense burden on families, society, and the healthcare system.In recent years, stem cell-derived exosomes have become a hot topic in tissue repair research. The combination of these exosomes with biomaterials allows for the preservation of their biological activity, leading to a significant improvement in their therapeutic efficacy. Among the numerous biomaterial options available, hydrogels stand out as promising candidates for loading exosomes, owing to their exceptional properties. Due to the lack of a comprehensive review on the subject matter, this review comprehensively summarizes the application and progress of combining stem cell-derived exosomes and hydrogels in promoting tissue damage repair in geriatric diseases. In addition, the challenges encountered in the field and potential prospects are presented for future advancements.

Locus coeruleus integrity is related to an exploitation-based decision-making bias in older adulthood.

Optimal decision-making balances exploration for new information against exploitation of known rewards, a process mediated by the locus coeruleus and its norepinephrine projections. We predicted that an exploitation-bias that emerges in older adulthood would be associated with lower microstructural integrity of the locus coeruleus. Leveraging in vivo histological methods from quantitative MRI-magnetic transfer saturation-we provide evidence that older age is associated with lower locus coeruleus integrity. Critically, we demonstrate that an exploitation bias in older adulthood, assessed with a foraging task, is sensitive and specific to lower locus coeruleus integrity. Because the locus coeruleus is uniquely vulnerable to Alzheimer's disease pathology, our findings suggest that aging, and a presymptomatic trajectory of Alzheimer's related decline, may fundamentally alter decision-making abilities in later life.

[LOWER EYELID BLEPHAROPLASTY].

INTRODUCTION: Eyelid blepharoplasty, including lower eyelid blepharoplasty, are among the most common aesthetic surgeries recently performed. In contrast to upper eyelid blepharoplasty, lower eyelid blepharoplasty is a surgery with mostly an aesthetic indication, in which patients bear all associated costs, and their expectations rise accordingly. Nevertheless, the complexity of the anatomy, the differences in the aging processes of the face and eyelids between patients, the diversity of surgical methods, and the expectations gap make the surgery more challenging in comparison to upper eyelid blepharoplasty. A comprehensive understanding of the eyelid anatomy and the surrounding tissues, as well as matching expectations alongside with thorough preoperative evaluation, are all essential for providing a more personal adjustment of the surgical method and avoiding complications and mental distress for both patients and surgeons. This article briefly reviews the anatomy and aging processes of the lower eyelids, the main surgical approaches, and their common complications. Moreover, we present a framework for how such complications can be avoided.

Associations Between Gait Speed and Fat Mass in Older Adults.

Purpose: Although both gait speed and fat mass are crucial for healthy aging, evidence suggests that the associations between these components remain unclear. Therefore, the main purpose of the study was to examine the associations between gait speed and fat mass. Patients and Methods: In this cross-sectional study, we recruited 643 older men and women aged >60 years. Fat mass was assessed using bioelectrical impedance analysis, while gait speed was determined by calculating the time an individual has taken to walk across a 4.6-m distance. Receiver operating characteristic (ROC) curves and odds ratios (OR) were performed to determine cut-off points and mutual associations. Results: In older men, the optimal threshold of gait speed to detect high level of fat mass was 1.40 m/s with the area under the curve (AUC) being 0.82 (95% CI 0.76-0.89, p < 0.001). In older women, the optimal cut-off point was 1.37 m/s (AUC = 0.85, 95% CI 0.81-0.90, p < 0.001). Older men and women who walked below the newly developed threshold were approximately 12 times more likely to have high level of fat. Conclusion: In summary, newly developed cut-off points of gait speed have adequate discriminatory ability to detect older men and women with high level of fat mass. Although gait speed may be considered as a satisfactory screening tool for fat mass, its utility in clinical practice needs to be further investigated.

The association between circadian syndrome and chronic kidney disease in an aging population: a 4-year follow-up study.

Introduction: Circadian syndrome (CircS) is proposed as a novel risk cluster based on reduced sleep duration, abdominal obesity, depression, hypertension, dyslipidemia and hyperglycemia. However, the association between CircS and chronic kidney disease (CKD) remains unclear. To investigate the cross-sectional and longitudinal association between CircS and CKD, this study was performed. Methods: A national prospective cohort (China Health and Retirement Longitudinal Study, CHARLS) was used in this study. To define CKD, the estimated glomerular filtration rate (eGFR) was calculated based on the 2012 CKD-EPI creatinine-cystatin C equation. Participants with eGFR <60 mL.min-1/1.73/m2 were diagnosed with CKD. Multivariate binary logistic regression was used to assess the cross-sectional association between CircS and CKD. Subgroup and interactive analyses were performed to determine the interactive effects of covariates. In the sensitivity analysis, the obese population was excluded and another method for calculating the eGFR was used to verify the robustness of previous findings. In addition, participants without CKD at baseline were followed up for four years to investigate the longitudinal relationship between CircS and CKD. Results: A total of 6355 participants were included in this study. In the full model, CircS was positively associated with CKD (OR = 1.28, 95% CI = 1.04-1.59, P < 0.05). As per one increase of CircS components, there was a 1.11-fold (95% CI = 1.04-1.18, P < 0.05) risk of prevalent CKD in the full model. A significant interactive effect of hyperuricemia in the CircS-CKD association (P for interaction < 0.01) was observed. Sensitivity analyses excluding the obese population and using the 2009 CKD-EPI creatinine equation to diagnose CKD supported the positive correlation between CircS and CKD. In the 2011-2015 follow-up cohort, the CircS group had a 2.18-fold risk of incident CKD (95% CI = 1.33-3.58, P < 0.01) in the full model. The OR was 1.29 (95% CI = 1.10-1.51, P < 0.001) with per one increase of CircS components. Conclusion: CircS is a risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

Daily singing of adult songbirds functions to maintain song performance independently of auditory feedback and age.

Many songbirds learn to produce songs through vocal practice in early life and continue to sing daily throughout their lifetime. While it is well-known that adult songbirds sing as part of their mating rituals, the functions of singing behavior outside of reproductive contexts remain unclear. Here, we investigated this issue in adult male zebra finches by suppressing their daily singing for two weeks and examining the effects on song performance. We found that singing suppression decreased the pitch, amplitude, and duration of songs, and that those song features substantially recovered through subsequent free singing. These reversible song changes were not dependent on auditory feedback or the age of the birds, contrasting with the adult song plasticity that has been reported previously. These results demonstrate that adult song structure is not stable without daily singing, and suggest that adult songbirds maintain song performance by preventing song changes through physical act of daily singing throughout their life. Such daily singing likely functions as vocal training to maintain the song production system in optimal conditions for song performance in reproductive contexts, similar to how human singers and athletes practice daily to maintain their performance.

Differential Effects of Aging on Regional Corpus Callosum Microstructure and the Modifying Influence of Pulse Pressure.

The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by cardiovascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anteroposterior gradient of vulnerability to aging that may be altered by the effects of cardiovascular health. In 174 healthy adults across the adult lifespan (mean age = 53.56 ± 18.90; range, 20-94 years old, 58.62% women), pulse pressure (calculated as participant's systolic minus diastolic blood pressure) was assessed to determine cardiovascular risk. A deterministic tractography approach via diffusion-weighted imaging was utilized to extract fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General linear models tested the effects of age, hypertension, and pulse pressure on these cross-sectional metrics. We observed no significant effect of hypertensive diagnosis on callosal microstructure. We found a significant main effect of age and an age-pulse pressure interaction whereby older age and elevated pulse pressure were associated with poorer FA, AD, and RD. Age effects revealed nonlinear components and occurred along an anteroposterior gradient of severity in the callosum. This gradient disappeared when pulse pressure was considered. These results indicate that age-related deterioration across the callosum is regionally variable and that pulse pressure, a proxy of arterial stiffness, exacerbates this aging pattern in a large lifespan cohort.