GEROSCIENCE 是一份双月刊、国际同行评审期刊，发表与衰老生物学研究和影响衰老的生物医学应用研究相关的文章。要考虑的文章范围包括进化生物学、生物物理学、遗传学、基因组学、蛋白质组学、分子生物学、细胞生物学、生物化学、内分泌学、免疫学、生理学、药理学、神经科学和心理学。

GeroScience is a bi-monthly international peer-reviewed journal that focuses on research in the biology of aging and biomedical applications related to aging. The scope of articles considered includes evolutionary biology, biophysics, genetics, genomics, proteomics, molecular biology, cell biology, biochemistry, endocrinology, immunology, physiology, pharmacology, neuroscience, and psychology.

GEROSCIENCE 是一本双月刊的国际同行评审期刊，专注于衰老生物学及其相关的生物医学应用研究。期刊接受的文章范围广泛，包括进化生物学、生物物理学、遗传学、基因组学、蛋白质组学、分子生物学、细胞生物学、生物化学、内分泌学、免疫学、生理学、药理学、神经科学和心理学等领域。

GeroScience

Postoperative delirium (POD) is a common neuropsychiatric complication in geriatric inpatients after hip fracture surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the relationship between preoperative biomarkers in serum and cerebrospinal fluid (CSF) and the development of POD in older hip fracture patients, exploring the possibility of integrating objective methods into future predictive models of delirium. Sixty hip fracture patients were recruited. Blood and CSF samples were collected at the time of spinal anesthesia when none of the subjects had delirium. Patients were assessed daily using the 4AT scale, and based on these results, they were divided into POD and non-POD groups. The Olink® platform was used to analyze 45 cytokines. Twenty-one patients (35%) developed POD. In the subsample of 30 patients on whom proteomic analyses were performed, a proteomic profile was associated with the incidence of POD. Chemokine (C-X-C motif) ligand 9 (CXCL9) had the strongest correlation between serum and CSF samples in patients with POD (rho = 0.663; p < 0.05). Although several cytokines in serum and CSF were associated with POD after hip fracture surgery in older adults, there was a significant association with lower preoperative levels of CXCL9 in CSF and serum. Despite the small sample size, this study provides preliminary evidence of the potential role of molecular biomarkers in POD, which may provide a basis for the development of new delirium predictive models.

Lucía Lozano-Vicario

Ángel Javier Muñoz-Vázquez

Robinson Ramírez-Vélez

Arkaitz Galbete-Jiménez

Joaquín Fernández-Irigoyen

Enrique Santamaría

Bernardo Abel Cedeno-Veloz

Fabricio Zambom-Ferraresi

Barbara C Van Munster

José Ramón Ortiz-Gómez

Ángel Manuel Hidalgo-Ovejero

Román Romero-Ortuno

Mikel Izquierdo

Nicolás Martínez-Velilla

Geroscience

Association of postoperative delirium with serum and cerebrospinal fluid proteomic profiles: a prospective cohort study in older hip fracture patients.

Cellular senescence is an important risk factor in the development of hepatic steatosis. Senolytics present therapeutic effects on age-related hepatic steatosis without eliminating senescent hepatocytes directly. Therefore, it highlights the need to find senolytics' therapeutic targets. Dysfunction of adipose tissue underlies the critical pathogenesis of lipotoxicity in the liver. However, the correlation between adipose tissue and hepatic steatosis during aging and its underlying molecular mechanism remains poorly understood. We explored the correlation between white adipose tissue (WAT) and the liver during aging and evaluated the effect of lipolysis of aged WAT on hepatic steatosis and hepatocyte senescence. We screened out the ideal senolytics for WAT and developed a WAT-targeted delivery system for senotherapy. We assessed senescence and lipolysis of WAT and hepatic lipid accumulation after treatment. The results displayed that aging accelerated cellular senescence and facilitated lipolysis of WAT. Free fatty acids (FFAs) generated by WAT during aging enhanced hepatic steatosis and induced hepatocyte senescence. The combined usage of dasatinib and quercetin was screened out as the ideal senolytics to eliminate senescent cells in WAT. To minimize non-specific distribution and enhance the effectiveness of senolytics, liposomes decorated with WAT affinity peptide P3 were constructed for senotherapy in vivo. In vivo study, WAT-targeted treatment eliminated senescent cells in WAT and reduced lipolysis, resulting in the alleviation of hepatic lipid accumulation and hepatocyte senescence when compared to non-targeted treatment, providing a novel tissue-targeted, effective and safe senotherapy for age-related hepatic steatosis.

Qi Tang

Xiaotao Xing

Haisen Huang

Jian Yang

Maojiao Li

Xun Xu

Xin Gao

Cheng Liang

Weidong Tian

Li Liao

Eliminating senescent cells by white adipose tissue-targeted senotherapy alleviates age-related hepatic steatosis through decreasing lipolysis.

通过靶向白色脂肪组织的衰老细胞疗法消除衰老细胞减轻了与年龄相关的肝脂肪变性，其机制为降低脂解作用。

Abstract Physical activity, including walking, has numerous health benefits in older adults, supported by a plethora of observational and interventional studies. Walking decreases the risk or severity of various health outcomes such as cardiovascular and cerebrovascular diseases, type 2 diabetes mellitus, cognitive impairment and dementia, while also improving mental well-being, sleep, and longevity. Dose-response relationships for walking duration and intensity are established for adverse cardiovascular outcomes. Walking’s favorable effects on cardiovascular risk factors are attributed to its impact on circulatory, cardiopulmonary, and immune function. Meeting current physical activity guidelines by walking briskly for 30 min per day for 5 days can reduce the risk of several age-associated diseases. Additionally, low-intensity physical exercise, including walking, exerts anti-aging effects and helps prevent age-related diseases, making it a powerful tool for promoting healthy aging. This is exemplified by the lifestyles of individuals in Blue Zones, regions of the world with the highest concentration of centenarians. Walking and other low-intensity physical activities contribute significantly to the longevity of individuals in these regions, with walking being an integral part of their daily lives. Thus, incorporating walking into daily routines and encouraging walking-based physical activity interventions can be an effective strategy for promoting healthy aging and improving health outcomes in all populations. The goal of this review is to provide an overview of the vast and consistent evidence supporting the health benefits of physical activity, with a specific focus on walking, and to discuss the impact of walking on various health outcomes, including the prevention of age-related diseases. Furthermore, this review will delve into the evidence on the impact of walking and low-intensity physical activity on specific molecular and cellular mechanisms of aging, providing insights into the underlying biological mechanisms through which walking exerts its beneficial anti-aging effects.

Zoltan Ungvari

Vince Fazekas-Pongor

Anna Csiszar

Setor K. Kunutsor

The multifaceted benefits of walking for healthy aging: from Blue Zones to molecular mechanisms

步行对健康老龄化的多方面益处：从蓝区到分子机制

Sleep maintains the function of the entire body through homeostasis. Chronic sleep deprivation (CSD) is a prime health concern in the modern world. Previous reports have shown that CSD has profound negative effects on brain vasculature at both the cellular and molecular levels, and that this is a major cause of cognitive dysfunction and early vascular ageing. However, correlations among sleep deprivation (SD), brain vascular changes and ageing have barely been looked into. This review attempts to correlate the alterations in the levels of major neurotransmitters (acetylcholine, adrenaline, GABA and glutamate) and signalling molecules (Sirt1, PGC1α, FOXO, P66shc, PARP1) in SD and changes in brain vasculature, cognitive dysfunction and early ageing. It also aims to connect SD-induced loss in the number of dendritic spines and their effects on alterations in synaptic plasticity, cognitive disabilities and early vascular ageing based on data available in scientific literature. To the best of our knowledge, this is the first article providing a pathophysiological basis to link SD to brain vascular ageing.

Arehally M. Mahalakshmi

Bipul Ray

Sunanda Tuladhar

Abid Bhat

Muhammed Bishir

Srinivasa Rao Bolla

Musthafa Mohamed Essa

Saravana Babu Chidambaram

Gilles J. Guillemin

Meena Kishore Sakharkar

Sleep, brain vascular health and ageing

睡眠、脑血管健康与衰老

Growth Differentiation Factor 15 (GDF-15) is a cytokine produced in response to tissue injury and inflammatory states that may capture distinct pathways between the risk factors aggregated within metabolic syndrome (MS) and the development of diabetes and cardiovascular disease. This work aims to study the association of MS and its components with GDF-15 among older adults, examining the roles of body fat distribution, glucose metabolism, and inflammation. Data were taken from the Seniors-ENRICA-2 study in Spain, which included 1938 non-institutionalized individuals aged ≥65 years free of diabetes and cardiovascular disease. MS was defined as the presence of ≥3 of the following components: high waist circumference, elevated fasting blood glucose levels, raised blood pressure, increased triglyceride levels, and low serum high-density lipoprotein (HDL) cholesterol. Statistical analyses were performed with linear regression models and adjusted for potential sociodemographic and lifestyle confounders. MS was associated with higher GDF-15 levels (fully adjusted mean increase [95% confidence interval] = 9.34% [5.16,13.7]). The MS components showing the strongest associations were high waist circumference (6.74% [2.97,10.6]), elevated glucose levels (4.91% [0.77,9.23]), and low HDL-cholesterol (8.13% [3.51,13.0]). High waist-to-hip ratio (7.07% [2.63,11.7]), urine albumin (12.1% [2.57,22.5]), and C-reactive protein (10.4% [3.89,17.3]) were also associated with increased GDF-15. In conclusion, MS was associated with higher GDF-15 levels in older adults. Abdominal obesity, hyperglycemia –possibly linked to microvascular disease, as inferred from elevated urine albumin–, low HDL-cholesterol, and inflammation were the main drivers of this association.

Adrián Carballo-Casla

Esther García-Esquinas

Antonio Buño-Soto

Ellen A. Struijk

Esther López-García

Fernando Rodríguez-Artalejo

Rosario Ortolá

Metabolic syndrome and Growth Differentiation Factor 15 in older adults

代谢综合征与老年人的生长分化因子15

The aim of the present study is to investigate differences in brain networks modulation during the pre- and post-sleep onset period, both within and between two groups of young and older individuals. Thirty-six healthy elderly and 40 young subjects participated. EEG signals were recorded during pre- and post-sleep onset periods and functional connectivity analysis, specifically focusing on the small world (SW) index, applied to EEG data (i.e., frequency bands) was examined. Significant differences in SW values were found between the pre-sleep and post-sleep onset phases in both young and older groups, with a reduction in the SW index in the theta band common to both groups. Additionally, an increase in the SW index in the beta band was exclusive to the elderly group during the post-sleep onset period, while an increase in the sigma band was exclusive to the young group. Furthermore, differences between the young and elderly groups were found during both phases, including a decrease in the SW index within the delta band, an increment in the sigma and beta bands in the elderly compared to the young group during the pre-sleep onset period, and a notable absence of sigma band modulation in the elderly group during the post-sleep onset condition. These findings provide insights into age-related changes in sleep-related brain network dynamics and their potential impact on sleep quality and cognitive functions, prompting interventions aimed at supporting healthy aging and addressing age-related cognitive decline.

Francesca Miraglia

Alessia Cacciotti

Fabrizio Vecchio

Serena Scarpelli

Maurizio Gorgoni

Luigi De Gennaro

Paolo Maria Rossini

EEG brain networks modulation during sleep onset: the effects of aging

睡眠起始期间的脑电图脑网络调制：老化的影响

Metabolic syndrome (MetS) has been linked to accelerated cognitive decline and Alzheimer's disease and related dementias (ADRDs) via cerebral small vessel disease (CSVD); however, this relation in MetS without overt cardiometabolic disease comorbidities is unknown and may represent a population amenable to preventative strategies. Our study aimed to determine risk profiles for neurocognitive decline and ADRDs in early-stage MetS with evidence of CSVD using the TriNetX electronic health records (EHR) research network. Patients aged 50 to 80 years old meeting MetS criteria were identified utilizing TriNetX data from 76 healthcare organizations. Propensity score matching controlled for demographic and confounding factors. Cohorts included MetS-only, non-MetS, and a MetS subset with evidence of CSVD (MetS-CSVD) created by clustering relevant ICD-codes for diagnoses, imaging, and lab work. Contingency analyses determined odds of developing neurocognitive decline, ADRDs, and CSVD in MetS vs non-MetS and MetS-CSVD vs. MetS-only, using odd ratios with 95% confidence intervals (p-value < 0.05). After propensity score matching, there were 57,347 men and 52,259 women in each of the MetS and non-MetS cohorts and 2,810 men and 2,862 women in each of the MetS-CSVD and MetS-only cohorts. Compared to non-MetS, the MetS cohort exhibited higher odds of developing neurocognitive decline (men: RR = 1.82, p < 0.001; women: RR = 1.34, p = 0.015) and CSVD (men: RR = 2.83, p < 0.001; women: RR = 2.14, p < 0.001), but only women exhibited significantly higher odds of developing ADRDs (men: RR = 1.13, p = 0.38; women: RR = 1.52, p < 0.001). Compared to MetS-only, the MetS-CSVD showed elevated odds in developing neurocognitive decline (men: RR = 1.81, p = 0.040; women: RR = 1.87, p = 0.018) and ADRDs (men: RR = 2.39, p = 0.009; women: RR = 1.65, p = 0.041). A large, predominantly US, sample of subclinical MetS demonstrated heightened odds for developing neurocognitive decline and ADRDs, with even higher odds when evidence of CSVD was also present. TriNetX facilitated a robust exploration of these associations, and our findings warrant further investigation of interventions that target this subclinical at-risk population.

Jigar Gosalia

Jocelyn M. Delgado Spicuzza

Christine K. Bowlus

James A. Pawelczyk

David N. Proctor

Linking metabolic syndrome, cerebral small vessel disease, and cognitive health: insights from a subclinical population study using TriNetX

链接代谢综合征、脑小血管疾病与认知健康：基于TriNetX的亚临床人群研究见解

The alarmingly high prevalence of obesity in older adults coupled with the negative health effects of chronic inflammation in both obesity and aging highlight the importance of studies investigating the impacts of obesity on age-related inflammation. Since shifts in peripheral T-cell metabolism and function drive systemic inflammation in both obesity and aging, we hypothesize that obesity impacts the Th17-dominated inflammaging profile we identified in lean subjects and thus modifies the anti-inflammatory effects of geroprotective drugs like metformin. New cytokine profiling data showed that CD4+ T cells from older people with obesity generate a profile that specifically excludes Th17 cytokines. Metformin failed to change the age-associated T-cell profile in obesity, despite lowering both mitochondrial respiration and reactive oxygen species (ROS) production. Metformin did not improve macroautophagy in T cells from older people with obesity, in sharp contrast to the ability of metformin to promote autophagy in T cells from older lean subjects. These data indicate that body mass index modifies the mechanisms supporting inflammaging in T cells from older subjects, and that metformin-mediated restoration of redox balance is insufficient to stem obesity-associated inflammaging. We conclude that obesity fundamentally changes the mechanisms that promote inflammaging, and thus obesity becomes a critical consideration for clinical trials of geroprotective agents such as metformin.

S. SantaCruz-Calvo

S. Saraswat

G. H. Kalantar

E. Zukowski

H. Marszalkowski

A. Javidan

F. Gholamrezaeinejad

L. P. Bharath

P. A. Kern

X. D. Zhang

B. S. Nikolajczyk

A unique inflammaging profile generated by T cells from people with obesity is metformin resistant

肥胖人群T细胞产生的独特炎症衰老特征对二甲双胍具有抗性

Abstract The differences in the association of objectively measured physical activity with disability between frail and non-frail older adults remain unclear. We (1) evaluated the dose-dependent relationship between daily steps and disability in older adults with and without frailty and (2) examined the interaction between steps and frailty status in relation to the risk of disability. This prospective study used data from 4065 adults aged ≥ 65 years from the Kyoto-Kameoka Study, Japan. The mean daily step count obtained using triaxial accelerometers across ≥ 4 days was recorded. Frailty was evaluated using the validated Kihon Checklist. Disability was identified using the long-term care insurance system’s nationally unified database, with data collected until November 30, 2016. Overall, 385 disabilities were recorded during a median follow-up period of 3.32 years (12,855 person-years). After adjusting for confounders, an inverse association was observed between daily step count and disability risk. The disability risk plateaued at 5,000–7,000 steps/day in non-frail people, whereas step counts showed an almost linear inverse relationship with disability risk in frail people. Low step counts (&lt; 5,000 steps) in frail people were more strongly associated with disability risk than were high step counts (≥ 5,000 steps) in non-frail people. The additive interaction between steps and frailty was associated with the relative excess risk of disability in frail people with low step counts (p for interaction = 0.015). The relationship between daily steps and disability differs between older adults with and without frailty, and the adverse effects of frailty on disability risk depend on physical activity.

Daiki Watanabe

Tsukasa Yoshida

Yuya Watanabe

Yosuke Yamada

Motohiko Miyachi

Misaka Kimura

Association of the interaction between daily step counts and frailty with disability in older adults

每日步数与虚弱之间的相互作用与老年人残疾的关联

The geroscience hypothesis proposes that underlying biological processes, such as the accumulation of senescent cells, have deleterious effects on multiple tissues and increase the risk of many chronic conditions with aging. Senescent cells produce heterogenous biomarkers, also called senescence-associated secretory phenotype (SASP). Circulating concentrations of senescence biomarkers may reflect an underlying burden of senescent cells in various tissues. Plasma levels of these proteins have been associated with increased mortality and poorer physical function. The associations of them with the incidence of major age-related conditions including heart failure, cardiovascular disease, stroke, and dementia, have not been studied. We measured 35 senescence biomarkers in baseline plasma samples from 1678 participants aged 70-79 years old in the longitudinal Health ABC cohort study. Clinical outcomes were ascertained and validated over an average 11.5 year follow-up. In models adjusted for age, sex, and race, higher levels of most of senescence biomarkers were associated with increased risk of all-cause mortality, mobility limitation, and heart failure. Several were also associated with an increased risk of coronary heart disease, stroke, and dementia. Very few were associated with the risk of cancer. Proteins that were selected by Lasso regression for each outcome that commonly included GDF15 and IL6, significantly improved the prediction of mortality, mobility limitation, and heart failure compared with age, sex, and race alone. These results indicate that levels of senescence biomarkers predict an increased risk of several age-related clinical outcomes and may identify individuals most likely to benefit from senotherapeutics.

Abbreviation	GeroScience
Journal Impact	5.49
Quartiles(Global)	GERIATRICS & GERONTOLOGY(Q1)

ISSN	2509-2715, 2509-2723
h-index	87

Publication Information	Publisher: Springer Science and Business Media Deutschland GmbH，Publishing cycle: 6 issues per year，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2017，Proportion of original research papers: 91.54%，Self Citation Rate:7.50%， Gold OA Rate: 47.87%

GeroScience

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