Abstract:
:Senescent cells (SCs) have been considered a source of age-related chronic sterile systemic inflammation and a target for anti-aging therapies. To understand mechanisms controlling the amount of SCs, we analyzed the phenomenon of rapid clearance of human senescent fibroblasts implanted into SCID mice, which can be overcome when SCs were embedded into alginate beads preventing them from immunocyte attack. To identify putative SC killers, we analyzed the content of cell populations in lavage and capsules formed around the SC-containing beads. One of the major cell types attracted by secretory factors of SCs was a subpopulation of macrophages characterized by p16(Ink4a) gene expression and β-galactosidase activity at pH6.0 (β-gal(pH6)), thus resembling SCs. Consistently, mice with p16(Ink4a) promoter-driven luciferase, developed bright luminescence of their peritoneal cavity within two weeks following implantation of SCs embedded in alginate beads. p16(Ink4a)/β-gal(pH6)-expressing cells had surface biomarkers of macrophages F4/80 and were sensitive to liposomal clodronate used for the selective killing of cells capable of phagocytosis. At the same time, clodronate failed to kill bona fide SCs generated in vitro by genotoxic stress. Old mice with elevated proportion of p16(Ink4a)/β-gal(pH6)-positive cells in their tissues demonstrated reduction of both following systemic clodronate treatment, indicating that a significant proportion of cells previously considered to be SCs are actually a subclass of macrophages. These observations point at a significant role of p16(Ink4a)/β-gal(pH6)-positive macrophages in aging, which previously was attributed solely to SCs. They require re-interpretation of the mechanisms underlying rejuvenating effects following eradication of p16(Ink4a)/β-gal(pH6)-positive cells and reconsideration of potential cellular target for anti-aging treatment.
journal_name
Aging (Albany NY)journal_title
Agingauthors
Hall BM,Balan V,Gleiberman AS,Strom E,Krasnov P,Virtuoso LP,Rydkina E,Vujcic S,Balan K,Gitlin I,Leonova K,Polinsky A,Chernova OB,Gudkov AVdoi
10.18632/aging.100991subject
Has Abstractpub_date
2016-07-01 00:00:00pages
1294-315issue
7issn
1945-4589pii
100991journal_volume
8pub_type
杂志文章相关文献
Aging-US文献大全abstract::Senescent cells secrete inflammatory cytokines, proteases, and other factors, which are indicated as senescence-associated secretory phenotype (SASP). There are contrasting studies on the role of the SASP in cancer. Studies suggested that cancer cells may misuse the senescent secretome for their growth. Other investig...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102172
更新日期:2019-08-14 00:00:00
abstract::Lung cancer remains the most lethal cancer worldwide because of its high metastasis potential. Epithelial-mesenchymal transition (EMT) is known as the first step of the metastasis cascade, but the potential regulatory mechanisms of EMT have not been clearly established. In this study, we first found that low CUEDC1 ex...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103329
更新日期:2020-10-25 00:00:00
abstract::Diabetic foot (DF) is a common complication of high severity for diabetes, a prevalent metabolic disorder that affects billions of people worldwide. Mesenchymal stem cells (MSCs) have a demonstrative therapeutic effect on DF, through their generation of pro-angiogenesis factors, like vascular endothelial growth factor...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102562
更新日期:2019-12-21 00:00:00
abstract::Sarcopenia is a hallmark of aging. Inflammation due to increased generation of cytokines such as TNFα, IL-1β and IL-6 has been implicated in the pathogenesis of sarcopenia. In skeletal muscle of C57BL/6 mice from 12 until 28 months of age, we observed a progressive reduction of myofiber cross sectional area, loss of t...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.202200
更新日期:2020-11-26 00:00:00
abstract::Long alpha-synuclein gene (SNCA) promoter (Rep1) allele-carriers are linked to higher risk for Parkinson's disease (PD) and faster motor progression. Non-motor symptoms including autonomic, neuropsychiatric, and sleep disorders are common in PD. However, the relationship between SNCA Rep1 microsatellite lengths and no...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.104111
更新日期:2020-10-20 00:00:00
abstract::Hepatocellular carcinoma (HCC) is a common cancer with very poor survival due to lack of reliable biomarker for early diagnosis. In this study, we investigated microRNA (miRNA) profile of whole blood with a custom microarray containing probes for 1849 miRNA species in a total 213 successive subjects who were divided i...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101253
更新日期:2017-06-27 00:00:00
abstract::Head and neck squamous cell carcinoma (HNSCC), a major histologic subtype of head and neck cancer, presents great mortality and morbidity worldwide. The aim of this study is to discover new potential biomarkers closely correlated with HNSCC progression. In this study, weighted gene co-expression network analysis was a...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102000
更新日期:2019-06-06 00:00:00
abstract::To evaluate the effects of short-term administration of enriched branched-chain amino acids (BCAAs) on subjects with pre-sarcopenia or sarcopenia, our quasi-experimental study enrolled 33 subjects (12 pre-sarcopenia/21 sarcopenia; 6 men/27 women; mean age 66.6 ± 10.3 years) to take one sachet (3.6 g) of enriched BCAA ...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103576
更新日期:2020-07-26 00:00:00
abstract::Epithelial-to-mesenchymal transition (EMT) is important in tumor invasiveness and metastasis. We aimed to determine prognostic value of six key EMT markers (CDH1, CDH2, SNAI1, SNAI2, VIM, TWIST1) in clear cell renal cell carcinoma (ccRCC). A total of 533 ccRCC patients with RNASeq data from The Cancer Genome Atlas (TC...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102660
更新日期:2020-01-08 00:00:00
abstract::In this study, we investigated the functional and clinical significance of the long non-coding RNA (lncRNA) FAM181A-AS1 in human gliomas. TCGA, GTEx and CGGA database analyses showed that high FAM181A-AS1 expression correlates with advanced tumor stage and poor survival of glioma patients. FAM181A-AS1 expression is hi...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103391
更新日期:2020-10-20 00:00:00
abstract::Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of neural crest cells in parts of the intestine. This study aims to investigate the association of vesicle-associated membrane protein 5 (VAMP5) and mutated in colorectal cancer (MCC) genetic polymorphisms and their correlated risks with HS...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101423
更新日期:2018-04-25 00:00:00
abstract::One important process in liver cancer growth and progression is angiogenesis. Vascular endothelial growth factor (VEGF) has the significant role in liver cancer angiogenesis. sFlt1 (soluble Fms-like tyrosine kinase-1) is the promising inhibitor of VEGF and can be used as the new method of inhibiting angiogenesis. MSCs...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101146
更新日期:2016-12-28 00:00:00
abstract::Hepatoblastoma (HB) is a malignant embryonal tumor of the liver that consists of heterogenous populations of stem/progenitor cells. Although circular RNAs (circRNAs) play an essential role in tumor development, the effects of circRNA on the proliferation of HB cells, especially cancer stem cells (CSCs), remain unclear...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103748
更新日期:2020-10-14 00:00:00
abstract::Age-associated cognitive impairment is a major health and social issue because of increasing aged population. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. In middle-aged healthy humans, fasting blood glucose levels in the upper no...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101148
更新日期:2016-12-28 00:00:00
abstract:OBJECTIVE:We analyzed clinical parameters and risk factors for coronavirus disease 2019 (COVID-19)-related liver damage. RESULTS:Of the 332 COVID-19 patients, 306 and 26 were included in the non-critical and critical groups, respectively. The median time from onset to admission was 4.0 (2.0-8.0) days. Of the 332 COVID...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103860
更新日期:2020-10-01 00:00:00
abstract::Senescence is a leading cause of age-related cataract (ARC). The current study indicated that the senescence-associated protein, p53, total laminin (LM), LMα4, and transforming growth factor-beta1 (TGF-β1) in the cataractous anterior lens capsules (ALCs) increase with the grades of ARC. In cataractous ALCs, patient ag...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101943
更新日期:2019-05-10 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is one of the most common motoneuronal disease, characterized by motoneuronal loss and progressive paralysis. Despite research efforts, ALS remains a fatal disease, with a survival of 2-5 years after disease onset. Numerous gene mutations have been correlated with both sporadic (sAL...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103561
更新日期:2020-06-24 00:00:00
abstract::Salvia miltiorrhiza bunge(SM) is a popular herb for alleviating menopausal symptoms, although the scientific evidence of applying SM to estrogen replacement therapy is limited. In this study, we characterized the estrogenic activity of SM using in vivo models of immature and ovariectomized (OVX) mice and performed in ...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101145
更新日期:2016-12-20 00:00:00
abstract::Growing evidence suggests that circRNAs exert a critical role in tumorigenesis and cancer progression. To date, the molecular mechanisms underlying circRNAs in triple-negative breast cancer (TNBC) are still poorly known. Here, circRNA expression profile was investigated by RNA sequencing in TNBC tissues and matched pa...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103311
更新日期:2020-06-04 00:00:00
abstract::Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and d...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101022
更新日期:2016-08-29 00:00:00
abstract::Multiple sclerosis is among the most serious inflammatory demyelinating diseases (IDD). Interleukin-23A (IL23A) regulates and coordinates the activities of immune cells by interacting with its receptor IL23R and plays key roles in the pathogenesis of immune inflammatory diseases. IDD, deemed to be a kind of autoimmune...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101058
更新日期:2016-11-26 00:00:00
abstract::Availability of methionine is known to modulate the rate of aging in model organisms, best illustrated by the observation that dietary methionine restriction extends the lifespan of rodents. However, the underlying mechanisms are incompletely understood. In eukaryotic cells, methionine can be converted to cysteine thr...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.100491
更新日期:2012-10-01 00:00:00
abstract::Heart failure is a global health problem that affects approximately 26 million people worldwide. As conventional diagnostic techniques for heart failure have been in practice with various limitations, it is necessary to develop novel diagnostic models to supplement existing methods. With advances and improvements in g...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.202405
更新日期:2020-12-26 00:00:00
abstract::Expansion of polyglutamine stretch in the huntingtin (HTT) protein is a major cause of Huntington's disease (HD). The polyglutamine part in HTT interacts with various proteins implicated in epigenetic regulation of genes, suggesting that mutant HTT may disturb the integrity of the epigenetic system. Here, we used a PC...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101193
更新日期:2017-03-12 00:00:00
abstract::The outbreak of coronavirus disease 2019 (COVID-19) has become a world-wide emergency. The severity of COVID-19 is highly correlated with its mortality rate. We aimed to disclose the clinical characteristics and prognostic factors of COVID-19 patients who developed severe COVID-19. The study enrolled cases (no=1848) w...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103931
更新日期:2020-10-14 00:00:00
abstract::Tubastatin A (TubA) is a highly selective histone deacetylase 6 (HDAC6) inhibitor. As expected, mouse germinal vesicle oocytes fail to extrude the first polar body following TubA treatment. However, a previous study demonstrated that homozygous Hdac6 knockout (KO) mice can be viable and fertile. Therefore, we asked wh...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.101867
更新日期:2019-03-26 00:00:00
abstract::Differences in microRNA (miRNA) expression after intracerebral hemorrhage (ICH) have been reported in human and animal models, and miRNAs are being investigated as a new treatment for inflammation and oxidative stress after ICH. In this study, we found that microRNA-183-5p expression was decreased in the mouse brain a...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.103343
更新日期:2020-06-29 00:00:00
abstract::Genetic studies using model organisms have shown that many long-lived mutants display impaired fitness, such as reduced fecundity and delayed development. However, in several wild animals, the association between longevity and fitness does not seem to be inevitable. Thus, the relationship between longevity and fitness...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.100960
更新日期:2016-05-01 00:00:00
abstract::The composition and relative abundances of immune cells in the tumor microenvironment are key factors affecting the progression of lung adenocarcinomas (LUADs) and the efficacy of immunotherapy. Using the cancer gene expression dataset from The Cancer Genome Atlas (TCGA) program, we scored stromal and immune cells for...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.202269
更新日期:2020-12-09 00:00:00
abstract::To investigate the relation of higher apolipoprotein B/apolipoprotein AI (apoB/AI) ratio with the risk of suffering intracranial atherosclerotic stenosis (ICAS) in both stroke and non-stroke population, we enrolled 1138 patients with acute ischemic stroke (359 with ICAS, 779 without ICAS) and 1072 non-stroke controls ...
journal_title:Aging
pub_type: 杂志文章
doi:10.18632/aging.102216
更新日期:2019-09-03 00:00:00