Abstract:
:The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci.
journal_name
Aging Celljournal_title
Aging cellauthors
Teumer A,Qi Q,Nethander M,Aschard H,Bandinelli S,Beekman M,Berndt SI,Bidlingmaier M,Broer L,CHARGE Longevity Working Group.,Cappola A,Ceda GP,Chanock S,Chen MH,Chen TC,Chen YD,Chung J,Del Greco Miglianico F,Eriksson Jdoi
10.1111/acel.12490subject
Has Abstractpub_date
2016-10-01 00:00:00pages
811-24issue
5eissn
1474-9718issn
1474-9726journal_volume
15pub_type
杂志文章,meta分析相关文献
AGING CELL文献大全abstract::The skeletal muscle fibre is a syncitium where each myonucleus regulates the gene products in a finite volume of the cytoplasm, i.e., the myonuclear domain (MND). We analysed aging- and gender-related effects on myonuclei organization and the MND size in single muscle fibres from six young (21-31 years) and nine old m...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00594.x
更新日期:2010-10-01 00:00:00
abstract::Short telomeres are thought to trigger senescence, most likely through a single - or a group of few - critically shortened telomeres. Such short telomeres are thought to result from a combination of gradual linear shortening resulting from the end replication problem, reflecting the division history of the cell, super...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00568.x
更新日期:2010-06-01 00:00:00
abstract::The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of d...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12344
更新日期:2015-08-01 00:00:00
abstract::Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here, we describe a large-scale effort to define molecular mechanisms that underlie genotype-spe...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12130
更新日期:2013-12-01 00:00:00
abstract::Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age-related disease. The molecula...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13159
更新日期:2020-06-01 00:00:00
abstract::Klotho is a recently discovered anti-aging gene. The purpose of this study was to investigate whether klotho gene transfer attenuates superoxide production and oxidative stress in rat aorta smooth muscle (RASM) cells. RASM cells were transfected with AAV plasmids carrying mouse klotho full-length cDNA (mKL) or LacZ as...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2012.00796.x
更新日期:2012-06-01 00:00:00
abstract::Alzheimer's disease (AD) is a terminal age-associated dementia characterized by early synaptic dysfunction and late neurodegeneration. Although the presence of plaques of fibrillar aggregates of the amyloid beta peptide (Abeta) is a signature of AD, evidence suggests that the preplaque small oligomeric Abeta promotes ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2008.00434.x
更新日期:2008-12-01 00:00:00
abstract::Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduc...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12327
更新日期:2015-06-01 00:00:00
abstract::Aging involves coordinated yet distinct changes in organs and systems throughout life, including changes in essential trace elements. However, how aging affects tissue element composition (ionome) and how these changes lead to dysfunction and disease remain unclear. Here, we quantified changes in the ionome across eig...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13119
更新日期:2020-05-01 00:00:00
abstract::The accumulation of mitochondrial DNA (mtDNA) mutations has been proposed as an underlying cause of the aging process. Such mutations are thought to be generated principally through mechanisms involving oxidative stress. Skin is frequently exposed to a potent mutagen in the form of ultraviolet (UV) radiation and mtDNA...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2007.00310.x
更新日期:2007-08-01 00:00:00
abstract::Cockayne syndrome (CS) is a rare hereditary multisystem disease characterized by neurological and development impairment, and premature aging. Cockayne syndrome cells are hypersensitive to oxidative stress, but the molecular mechanisms involved remain unresolved. Here we provide the first evidence that primary fibrobl...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2012.00815.x
更新日期:2012-06-01 00:00:00
abstract::We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5 month) and old (25 month) mice of multiple inbred strains (129sv, BALB/c, CBA, DBA, B6, C3H and B6C3F(1)). In the heart, age-related changes of five genes were studied throughout the mouse lifes...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2009.00496.x
更新日期:2009-08-01 00:00:00
abstract::Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating premature aging disease. Mouse models have been instrumental for understanding HGPS mechanisms and for testing therapies, which to date have had only marginal benefits in mice and patients. Barriers to developing effective therapies include the unknown etiol...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12852
更新日期:2019-02-01 00:00:00
abstract::Aging is associated with increased vulnerability to inflammatory challenge. However, the effects of altered inflammatory response on the metabolic status of tissues or organs are not well documented. In this study, we present evidence demonstrating that lipopolysaccharide (LPS)-induced upregulation of the inflammasome...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12305
更新日期:2015-08-01 00:00:00
abstract::Irregular menstrual cycles, reduced responses to exogenous hormonal treatments, and altered endocrine profiles (high FSH/high LH/low AMH) are observed in women with increasing age before menopause. In this study, because the granulosa cell-specific Nrg1 knockout mice (gcNrg1KO) presented ovarian and endocrine phenotyp...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12662
更新日期:2017-12-01 00:00:00
abstract::Neurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neu...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12701
更新日期:2018-02-01 00:00:00
abstract::With aging, the kidney develops a progressive deterioration of several structures and functions. Proximal tubular acidification is impaired in old rats with a decrease in the activity of brush border Na+/H+ exchange and a fall of H-ion flux measured with micropuncture experiments. In the present work we evaluate the c...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2006.00229.x
更新日期:2006-10-01 00:00:00
abstract::One of the hallmarks of aging is the progressive accumulation of senescent cells in organisms, which has been proposed to be a contributing factor to age-dependent organ dysfunction. We recently reported that Bruton's tyrosine kinase (BTK) is an upstream component of the p53 responses to DNA damage. BTK binds to and p...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13079
更新日期:2020-01-01 00:00:00
abstract::Intron retention (IR) is the least well-understood alternative splicing type in animals, and its prevalence and function in physiological and pathological processes have long been underestimated. Cellular senescence contributes to individual aging and age-related diseases and can also serve as an important cancer prev...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13276
更新日期:2020-12-01 00:00:00
abstract::Recent studies demonstrate that aging exacerbates hypertension-induced cognitive decline, but the specific age-related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether a...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12315
更新日期:2015-06-01 00:00:00
abstract::Lifespan varies dramatically among species, but the biological basis is not well understood. Previous studies in model organisms revealed the importance of nutrient sensing, mTOR, NAD/sirtuins, and insulin/IGF1 signaling in lifespan control. By studying life-history traits and transcriptomes of 14 Drosophila species d...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12740
更新日期:2018-08-01 00:00:00
abstract::The epidermis of the skin, acting as the primary physical barrier between self and environment, is a dynamic tissue whose maintenance is critical to the survival of an organism. Like most other tissues and organs, the epidermis is maintained and repaired by a population of resident somatic stem cells. The epidermal st...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2007.00318.x
更新日期:2007-08-01 00:00:00
abstract::Histone acetyltransferases (HATs) are important enzymes that transfer acetyl groups onto histones and thereby regulate both gene expression and chromosomal structures. Previous work has shown that the activation of sirtuins, which are histone deacetylases, can extend lifespan. This suggests that inhibiting HATs may ha...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13129
更新日期:2020-04-01 00:00:00
abstract::Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would ...
journal_title:Aging cell
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/acel.13039
更新日期:2019-12-01 00:00:00
abstract::Aging is associated with a large number of both phenotypic and molecular changes, but for most of these, it is not known whether these changes are detrimental, neutral, or protective. We have identified a conserved Caenorhabditis elegans GATA transcription factor/MTA-1 homolog egr-1 (lin-40) that extends lifespan and ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12179
更新日期:2014-04-01 00:00:00
abstract::Neurodegenerative diseases (ND) have been linked to the critical process in aging-cellular senescence. However, the temporal dynamics of cellular senescence in ND conditions is unresolved. Here, we show senescence features develop in human Huntington's disease (HD) neural stem cells (NSCs) and medium spiny neurons (MS...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13226
更新日期:2020-11-01 00:00:00
abstract::Impaired osteoblast function is involved in osteoporosis, and microRNA (miRNA) dysregulation may cause abnormal osteoblast osteogenic activity. However, the influence of miRNA on osteoblast activity and the underlying mechanisms remain elusive. In this study, miR-103-3p was found to be negatively correlated with bone ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13298
更新日期:2021-01-13 00:00:00
abstract::Dietary restriction (DR) and rapamycin extend healthspan and life span across multiple species. We have recently shown that DR in progeroid DNA repair-deficient mice dramatically extended healthspan and trippled life span. Here, we show that rapamycin, while significantly lowering mTOR signaling, failed to improve lif...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13302
更新日期:2021-01-23 00:00:00
abstract::The deleterious reactive carbonyls released upon oxidation of polyunsaturated fatty acids in biological membranes are believed to foster cellular aging. Comparative studies in mammals and birds have shown that the susceptibility to peroxidation of membrane lipids peroxidation index (PI) is negatively correlated with l...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2012.00847.x
更新日期:2012-10-01 00:00:00
abstract::Incidence of intracerebral hemorrhage (ICH) and brain iron accumulation increases with age. Excess iron accumulation in brain tissues post-ICH induces oxidative stress and neuronal damage. However, the mechanisms underlying iron deregulation in ICH, especially in the aged ICH model have not been well elucidated. Ferro...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13235
更新日期:2020-11-01 00:00:00