Abstract:
:Small body size has been associated with long life span in four stocks of mutant dwarf mice, and in two varieties of dietary restriction in rodents. In this study, small body size at ages 2-24 months was shown to be a significant predictor of life span in a genetically heterogeneous mouse population derived from four common inbred mouse strains. The association was strongest for weights measured early in adult life, and somewhat weaker, though still statistically significant, at later ages. The effect was seen both in males and females, and was replicated in an independent population of the same genetic background. Body size at ages 2-4 months was correlated with levels of serum leptin in both males and females, and with levels of IGF-I and thyroid hormone in females only. A genome scan showed the presence of polymorphic alleles on chromosomes 2, 6, 7 and 15 with significant effects on body weight at 2-4 months, at 10-12 months, or at both age ranges, showing that weight gain trajectory in this stock is under complex genetic control. Because it provides the earliest known predictor of life span, body weight may be usefully included in screens for induced mutations that alter aging. The evidence that weight in 2-month-old mice is a significant predictor of life span suggests that at least some of the lethal diseases of old age can be timed by factors that influence growth rate in juvenile rodents.
journal_name
Aging Celljournal_title
Aging cellauthors
Miller RA,Harper JM,Galecki A,Burke DTdoi
10.1046/j.1474-9728.2002.00006.xkeywords:
subject
Has Abstractpub_date
2002-10-01 00:00:00pages
22-9issue
1eissn
1474-9718issn
1474-9726journal_volume
1pub_type
杂志文章相关文献
AGING CELL文献大全abstract::With reduced thymic activity, the population of naïve T cells in humans is maintained by homeostatic proliferation throughout adult life. In young adults, naïve CD4 T cells have enormous proliferative potential and plasticity to differentiate into different lineages. Here, we explored whether naïve CD4 T-cell aging is...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12957
更新日期:2019-08-01 00:00:00
abstract::Oxidative modification of cellular components may contribute to tissue dysfunction during aging. In skeletal muscle, contractile activity increases the generation of reactive oxygen and nitrogen species (ROS). The question of whether contraction-induced ROS generation is further increased in skeletal muscle of the eld...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2006.00198.x
更新日期:2006-04-01 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
abstract::Brain mitochondrial function has been posited to decline with aging. In order to test this hypothesis, cortical and striatal mitochondria were isolated from Fischer 344 rats at 2, 5, 11, 24 and 33 months of age. Mitochondrial membrane potential remained stable through 24 months, declining slightly in mitochondria from...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2005.00156.x
更新日期:2005-06-01 00:00:00
abstract::Dietary restriction is arguably the most promising nonpharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other regulatory factors are involved. Here, we measured at the geno...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12749
更新日期:2018-06-01 00:00:00
abstract::A partial reduction in food intake has been found to increase lifespan in many different organisms. We report here a new dietary restriction regimen in the nematode Caenorhabditis elegans, based on the standard agar plate lifespan assay, in which adult worms are maintained in the absence of a bacterial food source. Th...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2006.00238.x
更新日期:2006-12-01 00:00:00
abstract::Little is known about how diet and energy metabolism interact in determination of lifespan under ad libitum feeding. From 12 weeks of age until death, male and female wild-type (WT) and transgenic (TG) mice with increased skeletal muscle mitochondrial uncoupling (HSA-mUCP1 mice) were fed one of three different semisyn...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00648.x
更新日期:2011-02-01 00:00:00
abstract::Older adults universally suffer from sarcopenia and approximately 60-70% are diabetic or prediabetic. Nonetheless, the mechanisms underlying these aging-related metabolic disorders are unknown. NFκB has been implicated in the pathogenesis of several aging-related pathologies including sarcopenia and type 2 diabetes an...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12613
更新日期:2017-08-01 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::Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise-induced improvement in insulin sensitivity and car...
journal_title:Aging cell
pub_type: 杂志文章,随机对照试验
doi:10.1111/acel.12880
更新日期:2019-02-01 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::Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understo...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12320
更新日期:2015-06-01 00:00:00
abstract::Older adults often show signs of impaired CD8+ T-cell immunity, reflected by weaker responses against new infections and vaccinations, and decreased protection against reinfection. This immune impairment is in part thought to be the consequence of a decrease in both T-cell numbers and repertoire diversity. If this is ...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/acel.13262
更新日期:2020-11-01 00:00:00
abstract::A serum biomarker of biological versus chronological age would have significant impact on clinical care. It could be used to identify individuals at risk of early-onset frailty or the multimorbidities associated with old age. It may also serve as a surrogate endpoint in clinical trials targeting mechanisms of aging. H...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12706
更新日期:2018-04-01 00:00:00
abstract::Cellular senescence is a cellular program that prevents the proliferation of cells at risk of neoplastic transformation. On the other hand, age-related accumulation of senescent cells promotes aging at least partially due to the senescence-associated secretory phenotype, whereby cells secrete high levels of inflammato...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/acel.12734
更新日期:2018-04-01 00:00:00
abstract::Protein synthesis is a regulated cellular process that links nutrients in the environment to organismal growth and development. Here we examine the role of genes that regulate mRNA translation in determining growth, reproduction, stress resistance and lifespan. Translational control of protein synthesis by regulators ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2006.00266.x
更新日期:2007-02-01 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::Endothelial oxidative stress develops with aging and reactive oxygen species impair endothelium-dependent relaxation (EDR) by decreasing nitric oxide (NO) availability. Endothelial KCa 3.1, which contributes to EDR, is upregulated by H2 O2 . We investigated whether KCa 3.1 upregulation compensates for diminished EDR t...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12502
更新日期:2016-10-01 00:00:00
abstract::This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for in-depth analysis. This year, the first quantitative estimate of evolutionary conservation of genetic effects on lifespan has pointed to the key importance of genes involved in prot...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/j.1474-9726.2008.00415.x
更新日期:2008-10-01 00:00:00
abstract::This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for both genome-wide and in-depth analysis. This year, protein interaction networks have been used in a new bioinformatic approach to identify novel genes that extend replicative lifesp...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2009.00498.x
更新日期:2009-09-01 00:00:00
abstract::Reactive oxygen species (ROS) play important signaling roles in metazoans, but also cause significant molecular damage. Animals tightly control ROS levels using sophisticated defense mechanisms, yet the transcriptional pathways that induce ROS defense remain incompletely understood. In the nematode Caenorhabditis eleg...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12154
更新日期:2014-02-01 00:00:00
abstract::Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting both the hippocampus and the cerebral cortex. Reduced synaptic density that occurs early in the disease process seems to be partially due to the overactivation of N-methyl-d-aspartate receptors (NMDARs) leading to excitotoxicity. Recently, ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2012.00848.x
更新日期:2012-10-01 00:00:00
abstract::Accumulation of DNA damage may play an essential role in both cellular senescence and organismal aging. The ability of cells to sense and repair DNA damage declines with age. However, the underlying molecular mechanism for this age-dependent decline is still elusive. To understand quantitative and qualitative changes ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2007.00354.x
更新日期:2008-01-01 00:00:00
abstract::A huge amount of evidence has implicated amyloid beta (A beta) peptides and other derivatives of the amyloid precursor protein (beta APP) as central to the pathogenesis of Alzheimer's disease (AD). It is also widely recognized that age is the most important risk factor for AD and that the innate immune system plays a ...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/j.1474-9728.2004.00101.x
更新日期:2004-08-01 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::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::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::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::Exposure to sub-lethal levels of stress, or hormesis, was a means to induce longevity. By screening for mutations that enhance resistance to multiple stresses, we identified multiple alleles of alpha-1,2-mannosidase I (mas1) which, in addition to promoting stress resistance, also extended longevity. Longevity enhancem...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2009.00471.x
更新日期:2009-08-01 00:00:00
abstract::Sequence variations in a variety of pro- or anti-inflammatory cytokine genes have been found to influence successful aging and longevity. Because of the role played by the transforming growth factor beta1 (TGF-beta1) cytokine in inflammation and regulation of immune responses, the variability of the TGF-beta1 gene may...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9728.2004.00129.x
更新日期:2004-12-01 00:00:00