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 reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.
journal_name
Aging Celljournal_title
Aging cellauthors
Golegaonkar S,Tabrez SS,Pandit A,Sethurathinam S,Jagadeeshaprasad MG,Bansode S,Sampathkumar SG,Kulkarni MJ,Mukhopadhyay Adoi
10.1111/acel.12327subject
Has Abstractpub_date
2015-06-01 00:00:00pages
463-73issue
3eissn
1474-9718issn
1474-9726journal_volume
14pub_type
杂志文章相关文献
AGING CELL文献大全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::Fibrosis is a hallmark of aging tissues which often leads to altered architecture and function. The ovary is the first organ to show overt signs of aging, including increased fibrosis in the ovarian stroma. How this fibrosis affects ovarian biomechanics and the underlying mechanisms are unknown. Using instrumental ind...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13259
更新日期:2020-11-01 00:00:00
abstract::Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, alt...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12742
更新日期:2018-06-01 00:00:00
abstract::Aging impairs arterial function through oxidative stress and diminished nitric oxide (NO) bioavailability. Life-long caloric restriction (CR) reduces oxidative stress, but its impact on arterial aging is incompletely understood. We tested the hypothesis that life-long CR attenuates key features of arterial aging. Bloo...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12103
更新日期:2013-10-01 00:00:00
abstract::Nutrient availability influences an organism's life history with profound effects on metabolism and lifespan. The association between a healthy lifespan and metabolism is incompletely understood, but a central factor is glucose metabolism. Although glucose is an important cellular energy source, glucose restriction is...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2012.00855.x
更新日期:2012-10-01 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::Extending lifespan by lowering ambient temperature in the habitat has been shown in a variety of organisms. Its mechanism, however, remains elusive. In this study, we examined the survivorship and the aging process of the annual fish (Nothobranchius rachovii) reared under high (30 degrees C), moderate (25 degrees C) a...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2009.00525.x
更新日期:2009-12-01 00:00:00
abstract::In a previous study, we reported that a deficiency in MnSOD activity (approximately 80% reduction) targeted to type IIB skeletal muscle fibers was sufficient to elevate oxidative stress and to reduce muscle function in young adult mice (TnIFastCreSod2(fl/fl) mice). In this study, we used TnIFastCreSod2(fl/fl) mice to ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2011.00695.x
更新日期:2011-06-01 00:00:00
abstract::Fat tissue, frequently the largest organ in humans, is at the nexus of mechanisms involved in longevity and age-related metabolic dysfunction. Fat distribution and function change dramatically throughout life. Obesity is associated with accelerated onset of diseases common in old age, while fat ablation and certain mu...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1111/j.1474-9726.2010.00608.x
更新日期:2010-10-01 00:00:00
abstract::Growth hormone receptor knockout (GHRKO) mice are remarkably long-lived and have improved glucose homeostasis along with altered energy metabolism which manifests through decreased respiratory quotient (RQ) and increased oxygen consumption (VO2 ). Short-term exposure of these animals to increased environmental tempera...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13123
更新日期:2020-05-01 00:00:00
abstract::The mitochondrial theory of aging is based around the idea of a vicious cycle, in which somatic mutation of mtDNA engenders respiratory chain dysfunction, enhancing the production of DNA-damaging oxygen radicals. In turn, this is proposed to result in the accumulation of further mtDNA mutations. Finally, a bioenergeti...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1046/j.1474-9728.2003.00032.x
更新日期:2003-02-01 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::Summary We address the problem of establishing a survival schedule for wild populations. A demographic key identity is established, leading to a method whereby age-specific survival and mortality can be deduced from a marked cohort life table established for individuals that are randomly sampled at unknown age and mar...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9728.2004.00096.x
更新日期:2004-06-01 00:00:00
abstract::Aging causes cardiac dysfunction, often leading to heart failure and death. The molecular basis of age-associated changes in cardiac structure and function is largely unknown. The fruit fly, Drosophila melanogaster, is well-suited to investigate the genetics of cardiac aging. Flies age rapidly over the course of weeks...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12559
更新日期:2017-02-01 00:00:00
abstract::Accumulating evidence suggests a role for microRNAs (miRNAs) in regulating various processes of mammalian postnatal development and aging. To investigate the changes in blood-based miRNA expression from preterm infants to adulthood, we compared 365 miRNA expression profiles in a screening set of preterm infants and ad...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12225
更新日期:2014-08-01 00:00:00
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::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::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::Neuropeptide Y (NPY) is an orexigenic peptide that plays an essential role in caloric restriction (CR)-mediated lifespan extension. However, the mechanisms underlying the NPY-mediated effects in CR are poorly defined. Here, we report that NPY deficiency in male mice during CR increases mortality in association with li...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12558
更新日期:2017-04-01 00:00:00
abstract::Age-related increase in L-type Ca(2+) channel (LTCC) expression in hippocampal pyramidal neurons has been hypothesized to underlie the increased Ca(2+) influx and subsequent reduced intrinsic neuronal excitability of these neurons that lead to age-related cognitive deficits. Here, using specific antibodies against Cav...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12157
更新日期:2014-02-01 00:00:00
abstract::Methionine residues in proteins react readily with reactive oxygen species making them particularly sensitive to oxidation. However, because oxidized methionine can be reduced back in a catalyzed reaction, it has been suggested that methionine residues act as oxidant scavengers, protecting not only the proteins where ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2010.00657.x
更新日期:2011-04-01 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::Adequate energy stores are essential for survival, and sophisticated neuroendocrine mechanisms evolved to stimulate foraging in response to nutrient deprivation. Food search behavior is usually investigated in young animals, and it is not known how aging alters this behavior. To address this question in Drosophila mel...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12361
更新日期:2015-10-01 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::Immunosenescence, the age-related decline in immune response, is a well-known consequence of aging. To date, most studies of age-related changes in immune response focused on the cellular and physiological bases of this decline; we have virtually no understanding of the genetic basis of age-related changes in the immu...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2006.00219.x
更新日期:2006-08-01 00:00:00
abstract::Alogliptin is a commonly prescribed drug treating patients with type 2 diabetes. Here, we show that long-term intervention with alogliptin (0.03% w/w in diet) improves survival and health of mice on a high-fat diet. Alogliptin intervention takes beneficial effects associated with longevity, including increased insulin...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.12883
更新日期:2019-04-01 00:00:00
abstract::The frequently quoted figure for the fractional univalent reduction of oxygen to superoxide in mitochondria is certainly too high by at least one order of magnitude. This is so because the higher number (2%) was derived from mitochondria whose cytochrome c oxidase was blocked with cyanide. Nevertheless, even the more ...
journal_title:Aging cell
pub_type: 杂志文章,评审
doi:10.1046/j.1474-9728.2003.00075.x
更新日期:2004-02-01 00:00:00
abstract::Long-term calorie restriction (CR) has numerous benefits; however, effects of CR on susceptibility to intact pathogens are not well understood. Because CR enhances immune function of laboratory mice (Mus musculus), it was hypothesized that mice subjected to CR would be less susceptible to experimental infections of th...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/j.1474-9726.2007.00345.x
更新日期:2007-12-01 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::The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late-onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of APOE has a neuroprotective effect, it is associated with ...
journal_title:Aging cell
pub_type: 杂志文章
doi:10.1111/acel.13023
更新日期:2019-12-01 00:00:00