AGING CELL 的目标是发表最高质量的创新研究，解决衰老生物学的基本问题。为了在 AGING CELL 上发表，这项工作必须为理解老龄化提供重大的新贡献，并引起社区的普遍兴趣。 AGING CELL 力求涵盖老年科学的所有领域，突出揭示衰老过程的机制方面的研究，以及衰老与年龄相关疾病之间的联系。

Aging Cell aims to publish high-quality innovative research that addresses fundamental issues in the biology of aging. To be published in Aging Cell, the work must provide significant new contributions to the understanding of aging and garner broad interest within the community. Aging Cell seeks to cover all areas of geroscience, with a particular emphasis on research that reveals the mechanisms of the aging process and the connections between aging and age-related diseases.

《Aging Cell》旨在发表高质量的创新研究，解决衰老生物学中的基本问题。为了在《Aging Cell》上发表，研究必须为理解老龄化提供重要的新贡献，并引起学术界的广泛关注。《Aging Cell》力求涵盖老年科学的各个领域，特别强调揭示衰老过程机制的研究，以及衰老与年龄相关疾病之间的关系。

Aging Cell

The field of research on cellular senescence experienced a rapid expansion from being primarily focused onin vitroaspects of aging to the vast territories of animal and clinical research. Cellular senescence is defined by a set of markers, many of which are present and accumulate in a gradual manner prior to senescence induction or are found outside of the context of cellular senescence. These markers are now used to measure the impact of cellular senescence on aging and disease as well as outcomes of anti‐senescence interventions, many of which are at the stage of clinical trials. It is thus of primary importance to discuss their specificity as well as their role in the establishment of senescence. Here, the presence and role of senescence markers are described in cells prior to cell cycle arrest, especially in the context of replicative aging andin vivoconditions. Specifically, this review article seeks to describe the process of “cellular aging”: the progression of internal changes occurring in primary cells leading to the induction of cellular senescence and culminating in cell death. Phenotypic changes associated with aging prior to senescence induction will be characterized, as well as their effect on the induction of cell senescence and the final fate of cells reviewed. Using published datasets on assessments of senescence markersin vivo, it will be described how disparities between quantifications can be explained by the concept of cellular aging. Finally, throughout the article the applicational value of broadening cellular senescence paradigm will be discussed.

Mikolaj Ogrodnik

Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo

Abstract Alzheimer's disease (AD) is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited. Over‐activation of N‐methyl‐D‐aspartate (NMDA) receptors, amyloid β (Aβ) aggregation, a decrease in cerebral blood flow (CBF), and downstream pathological events play important roles in the disease progression of AD. In the present study, MN‐08, a novel memantine nitrate, was found to inhibit Aβ accumulation, prevent neuronal and dendritic spine loss, and consequently attenuate cognitive deficits in 2‐month‐old APP/PS1 transgenic mice (for a 6‐month preventative course) and in the 8‐month‐old triple‐transgenic (3×Tg‐AD) mice (for a 4‐month therapeutic course). In vitro, MN‐08 could bind to and antagonize NMDA receptors, inhibit the calcium influx, and reverse the dysregulations of ERK and PI3K/Akt/GSK3β pathway, subsequently preventing glutamate‐induced neuronal loss. In addition, MN‐08 had favorable pharmacokinetics, blood‐brain barrier penetration, and safety profiles in rats and beagle dogs. These findings suggest that the novel memantine nitrate MN‐08 may be a useful therapeutic agent for AD.

Liangmiao Wu

Xinhua Zhou

Yiwan Cao

Shing Hung MAK

Ling Zha

Ning Li

Zhiyang Su

Yifan Han

Yuqiang Wang

Maggie Pui Man Hoi

Yewei Sun

Gaoxiao Zhang

Zaijun Zhang

Xifei Yang

Therapeutic efficacy of novel memantine nitrate MN‐08 in animal models of Alzheimer’s disease

Sleep has been associated with aging and relevant health outcomes, but the causal relationship remains inconclusive. In this study, we investigated the associations of sleep behaviors with biological ages (BAs) among 363,886 middle and elderly adults from UK Biobank. Sleep index (0 [worst]-6 [best]) of each participant was retrieved from the following six sleep behaviors: snoring, chronotype, daytime sleepiness, sleep duration, insomnia, and difficulties in getting up. Two BAs, the KDM-biological age and PhenoAge, were estimated by corresponding algorithms based on clinical traits, and their residual discrepancies with chronological age were defined as the age accelerations (AAs). We first observed negative associations between the sleep index and the two AAs, and demonstrated that the change of AAs could be the consequence of sleep quality using Mendelian randomization with genetic risk scores of sleep index and BAs. Particularly, a one-unit increase in sleep index was associated with 0.104- and 0.119-year decreases in KDM-biological AA and PhenoAge acceleration, respectively. Air pollution is another key driver of aging. We further observed significant independent and joint effects of sleep and air pollution (PM2.5 and NO2 ) on AAs. Sleep quality also showed a modifying effect on the associations of elevated PM2.5 and NO2 levels with accelerated AAs. For instance, an interquartile range increase in PM2.5 level was associated with 0.009-, 0.044-, and 0.074-year increase in PhenoAge acceleration among people with high (5-6), medium (3-4), and low (0-2) sleep index, respectively. Our findings elucidate that better sleep quality could lessen accelerated biological aging resulting from air pollution.

Xu Gao

Ninghao Huang

Xinbiao Guo

Tao Huang

Role of sleep quality in the acceleration of biological aging and its potential for preventive interaction on air pollution insults: Findings from the UK Biobank cohort

睡眠质量在加速生物衰老中的作用及其对空气污染损害的预防性交互潜力：来自英国生物银行队列的研究发现

Abstract Osteoarthritis (OA) is a heterogeneous disease that is extremely hard to cure owing to its complex regulation network of pathogenesis, especially cartilage degeneration. FBXO21 is a subunit of ubiquitin E3 ligases that degrades P‐glycoprotein and EID1 by ubiquitination and activates the JNK and p38 pathways; however, its role in OA remains unknown. Here, the main objective of this study was to evaluate the potential effects and mechanism of FBXO21 in OA degeneration, we revealed that FBXO21 is upregulated in the cartilage of patients with OA, aging, and monosodium iodoacetate‐induced OA rats, and chondrocytes treated with interleukin‐1β, tumor necrosis factor‐α, and lipopolysaccharide. Moreover, the in vivo and in vitro knockdown of FBXO21 suppressed OA‐related cartilage degeneration, as evidenced by activated autophagy, upregulated anabolism, alleviated apoptosis, and downregulated catabolism. In contrast, its overexpression promoted OA‐related cartilage degeneration. In addition, using mass spectrometry and co‐immunoprecipitation assay, we demonstrated that the downstream mechanism of FBXO21 inhibits autophagy by interacting with and phosphorylating ERK. Furthermore, FBXO21 alleviated anabolism and enhanced apoptosis and catabolism by inhibiting autophagy in rat chondrocytes. Interestingly, for its upstream mechanism, JUNB promoted FBXO21 expression by directly targeting the FBXO21 promoter, thus further accelerating cartilage degeneration in SW1353 cells and rat chondrocytes. Overall, our findings reveal that the JUNB‐FBXO21‐ERK axis regulates OA apoptosis and cartilage matrix metabolism by inhibiting autophagy. Therefore, FBXO21 is an attractive target for regulating OA pathogenesis, and its knockdown may provide a novel targeted therapy for OA.

Zhiming Lin

Jianing Miao

Tao Zhang

Ming He

Ziyuan Wang

Xinyuan Feng

Lunhao Bai

JUNB‐FBXO21‐ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy

JUNB‐FBXO21‐ERK轴通过抑制自噬促进骨关节炎中的软骨退化

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by nuclear envelope alterations that lead to accelerated aging and premature death. Several studies have linked health and longevity to cell-extrinsic mechanisms, highlighting the relevance of circulating factors in the aging process as well as in age-related diseases. We performed a global plasma proteomic analysis in two preclinical progeroid models (LmnaG609G/G609G and Zmpste24-/- mice) using aptamer-based proteomic technology. Pathways related to the extracellular matrix, growth factor response and calcium ion binding were among the most enriched in the proteomic signature of progeroid samples compared to controls. Despite the global downregulation trend found in the plasma proteome of progeroid mice, several proteins associated with cardiovascular disease, the main cause of death in HGPS, were upregulated. We also developed a chronological age predictor using plasma proteome data from a cohort of healthy mice (aged 1-30 months), that reported an age acceleration when applied to progeroid mice, indicating that these mice exhibit an "old" plasma proteomic signature. Furthermore, when compared to naturally-aged mice, a great proportion of differentially expressed circulating proteins in progeroid mice were specific to premature aging, highlighting secretome-associated differences between physiological and accelerated aging. This is the first large-scale profiling of the plasma proteome in progeroid mice, which provides an extensive list of candidate circulating plasma proteins as potential biomarkers and/or therapeutic targets for further exploration and hypothesis generation in the context of both physiological and premature aging.

Diego Quintana‐Torres

Alejandra Valle‐Cao

Pablo Bousquets‐Muñoz

Sandra Freitas‐Rodríguez

Francisco Rodríguez

Alejandro Lucia

Carlos López‐Otín

Alejandro López‐Soto

Alicia R. Folgueras

The secretome atlas of two mouse models of progeria

两种小鼠早衰模型的分泌蛋白组图谱

Abstract Ultraviolet B (UVB) radiation is a major contributor to skin photoaging. Although mainly absorbed by the epidermis, UVB photons managing to penetrate the upper dermis affect human dermal fibroblasts (HDFs), leading, among others, to the accumulation of senescent cells. In vitro studies have shown that repeated exposures to subcytotoxic UVB radiation doses provoke HDFs' premature senescence shortly after the end of the treatment period. Here, we found that repetitive exposures to non‐cytotoxic UVB radiation doses after several days lead to mixed cultures, containing both senescent cells and fibroblasts resisting senescence. “Resistant” fibroblasts were more resilient to a novel intense UVB radiation stimulus. RNA‐seq analysis revealed that ERCC6, encoding Cockayne syndrome group B (CSB) protein, is up‐regulated in resistant HDFs compared to young and senescent cells. CSB was found to be a key molecule conferring protection toward UVB‐induced cytotoxicity and senescence, as siRNA‐mediated CSB loss‐of‐expression rendered HDFs significantly more susceptible to a high UVB radiation dose, while cells from a CSB‐deficient patient were found to be more sensitive to UVB‐mediated toxicity, as well as senescence. UVB‐resistant HDFs remained normal (able to undergo replicative senescence) and non‐tumorigenic. Even though they formed a distinct population in‐between young and senescent cells, resistant HDFs retained numerous tissue‐impairing characteristics of the senescence‐associated secretory phenotype, including increased matrix metalloprotease activity and promotion of epidermoid tumor xenografts in immunodeficient mice. Collectively, here we describe a novel subpopulation of HDFs showing increased resistance to UVB‐mediated premature senescence while retaining undesirable traits that may negatively affect skin homeostasis.

Asimina Fotopoulou

Maria T. Angelopoulou

Harris Pratsinis

Eleni Mavrogonatou

Dimitris Kletsas

A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation‐mediated premature senescence

过表达Cockayne综合征B组蛋白的一组人皮肤成纤维细胞抵抗UVB辐射介导的早衰

Abstract Calorie restriction (CR) and physical exercise (EX) are well‐established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long‐term follow‐up. This study compared BioAge biomarkers in 41 middle‐aged and older adult long‐term CR practitioners, 41 age‐ and sex‐matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood‐biomarkers. Additionally, a subset of participants (12 CR, 11 EX, and 12 WD) underwent multi‐omic profiling, including DNA methylation and RNAseq of colon mucosa, blood metabolomics, and stool metagenomics. A group of six young WD subjects (yWD) served as a reference for BioAge calculation using Mahalanobis distance across six omic layers. The results demonstrated consistently lower BioAge biomarkers in both CR and EX groups compared to WD controls across all layers. CR participants exhibited lower BioAge in gut microbiome and blood‐derived omics, while EX participants had lower BioAge in colon mucosa‐derived epigenetic and transcriptomic markers, suggesting potential tissue‐specific effects. Multi‐omic pathway enrichment analyses suggested both shared and intervention‐specific mechanisms, including oxidative stress and basal transcription as common pathways, with ether lipid metabolism uniquely enriched in CR. Despite limitations due to sample size, these findings contribute to the broader understanding of the potential anti‐aging effects of CR and EX, offering promising directions for further research.

Giovanni Fiorito

Valeria Tosti

Silvia Polidoro

Beatrice Bertozzi

Nicola Veronese

Edda Cava

Francesco Spelta

Laura Piccio

Dayna S. Early

Daniel Raftery

Paolo Vineis

Luigi Fontana

Multi‐omic analysis of biological aging biomarkers in long‐term calorie restriction and endurance exercise practitioners: A cross‐sectional study

长期热量限制与耐力运动实践者生物衰老标志物的多组学分析：一项横断面研究

Aging is tightly associated with reduced immune protection but increased risk of autoimmunity and inflammatory conditions. Regulatory T cells are one of the key cells to maintaining immune homeostasis. The age-dependent changes in CD4

Saranya Srinivasan

Shruti Mishra

Kenneth Ka‐Ho Fan

Liwen Wang

John Im

Courtney Segura

Neelam Mukherjee

Gang Huang

Manjeet Rao

Chaoyu Ma

Nu Zhang

Age‐Dependent Bi‐Phasic Dynamics of Ly49+<scp>CD8</scp>+ Regulatory T Cell Population

年龄依赖的双相动态Ly49+CD8+调节性T细胞群体

The oxidative stress-induced premature senescence of trabecular meshwork (TM) represents a pivotal risk factor for the development of glucocorticoid-induced glaucoma (GIG). This study aimed to elucidate the pathogenesis of TM senescence in GIG. MethodsIntraocular pressure (IOP), transmission electron microscopy and senescence-associated protein expression in TM were evaluated in GIG mice. Protein expression of phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and monoamine oxidase A (MAOA), phosphorylation of AKT were quantified. ROS and mitochondrial superoxide levels were measured to evaluate cellular oxidative stress. Cell cycle analysis, β-galactosidase staining, senescence-associated protein expression were employed to assess the aging status of primary human trabecular meshwork cells (pHTMs). ResultsmRNA-seq and KEGG analysis indicating PI3K/AKT pathway as a key regulator in TM of GIG. PI3K inhibitor significantly prevented IOP elevation and abnormal mitochondrial morphology of TM in the GIG mouse model. PI3K inhibitor or selective silencing of PIK3R1 alleviated dexamethasone (DEX)-induced oxidative stress, also mitochondrial dysfunction, inhibiting MAOA expression in pHTMs. The same phenomenon was observed in the GIG models with inhibition of MAOA. Further KEGG analysis indicates that cellular senescence is the key factor in the pathogenesis of GIG. TM senescence was observed in both GIG mouse and cell models. Inhibition of the PI3K/AKT/MAOA pathway significantly alleviated DEX-induced premature cellular senescence of TM in GIG models. Glucocorticoids activated the PI3K/AKT/MAOA pathway, leading to mitochondrial dysfunction, oxidative stress, and premature aging in TM, elevating IOP. This mechanism could be associated with the onset and progression of GIG, providing a potential approach for its treatment.

Pengyu Zhang

Nan Zhang

Yixin Hu

Xizhi Deng

Min Zhu

Cheng Lai

Wen Zeng

Min Ke

Role of <scp>PI3K</scp>/<scp>AKT</scp>/<scp>MAOA</scp> in glucocorticoid‐induced oxidative stress and associated premature senescence of the trabecular meshwork

<scp>PI3K</scp>/<scp>AKT</scp>/<scp>MAOA</scp>在糖皮质激素诱导的氧化应激及小梁网相关早衰中的作用

Abstract The mitochondrial genome (mtDNA) is an important source of inherited extranuclear variation. Clonal increases in mtDNA mutation heteroplasmy have been implicated in aging and disease, although the impact of this shift on cell function is challenging to assess. Reprogramming to pluripotency affects mtDNA mutation heteroplasmy. We reprogrammed three human fibroblast lines with known heteroplasmy for deleterious mtDNA point or deletion mutations. Quantification of mutation heteroplasmy in the resulting 76 induced pluripotent stem cell (iPSC) clones yielded a bimodal distribution, creating three sets of clones with high levels or absent mutation heteroplasmy with matched nuclear genomes. iPSC clones with elevated deletion mutation heteroplasmy show altered growth dynamics, which persist in iPSC‐derived progenitor cells. We identify transcriptomic and metabolic shifts consistent with increased investment in neutral lipid synthesis as well as increased epigenetic age in high mtDNA deletion mutation iPSC, consistent with changes occurring in cellular aging. Together, these data demonstrate that high mtDNA mutation heteroplasmy induces changes occurring in cellular aging.

Amy R. Vandiver

Alejandro Torres

Amberly Sanden

Thang L. Nguyen

Jasmine Gasilla

Mary T. Doan

Vahan Martirosian

Austin Hoang

Jonathan Wanagat

Michael A. Teitell

Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny

线粒体突变异质性增加诱导多能干细胞及其分化后代的老化表型

Abbreviation
Journal Impact	7.96
Quartiles(Global)	GERIATRICS & GERONTOLOGY(Q1)

ISSN	1474-9718, 1474-9726
h-index	173
Top Journals	Yes

Publication Information	Publisher: Wiley-Blackwell Publishing Ltd，Publishing cycle: Bimonthly，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2002，Proportion of original research papers: 91.10%，Self Citation Rate:2.50%， Gold OA Rate: 72.09%
Journal Fees	$3350Details
Average review cycle	网友分享经验：平均2月
Average recruitment ratio	网友分享经验：很难

Aging Cell

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Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo

Therapeutic efficacy of novel memantine nitrate MN‐08 in animal models of Alzheimer’s disease

Role of sleep quality in the acceleration of biological aging and its potential for preventive interaction on air pollution insults: Findings from the UK Biobank cohort

JUNB‐FBXO21‐ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy

The secretome atlas of two mouse models of progeria

A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation‐mediated premature senescence

Multi‐omic analysis of biological aging biomarkers in long‐term calorie restriction and endurance exercise practitioners: A cross‐sectional study

Age‐Dependent Bi‐Phasic Dynamics of Ly49⁺CD8⁺ Regulatory T Cell Population

Role of PI3K/AKT/MAOA in glucocorticoid‐induced oxidative stress and associated premature senescence of the trabecular meshwork

Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny

Aging Cell

Journal Citation Format

A journal article with 1 author

A journal article with 2 authors

A journal article with 3 authors

A journal article with 5 or more authors

Books Citation Format

Thesis Citation Format

Web sites Citation Format

Patent Citation Format

Staying up late manually editing references? ivySCI automatically matches journals and helps you generate references with a single click.

Share Submission Experience

Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo

Therapeutic efficacy of novel memantine nitrate MN‐08 in animal models of Alzheimer’s disease

Role of sleep quality in the acceleration of biological aging and its potential for preventive interaction on air pollution insults: Findings from the UK Biobank cohort

JUNB‐FBXO21‐ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy

The secretome atlas of two mouse models of progeria

A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation‐mediated premature senescence

Multi‐omic analysis of biological aging biomarkers in long‐term calorie restriction and endurance exercise practitioners: A cross‐sectional study

Age‐Dependent Bi‐Phasic Dynamics of Ly49+CD8+ Regulatory T Cell Population

Role of PI3K/AKT/MAOA in glucocorticoid‐induced oxidative stress and associated premature senescence of the trabecular meshwork

Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny

Age‐Dependent Bi‐Phasic Dynamics of Ly49⁺CD8⁺ Regulatory T Cell Population