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101.
102.
Martin Weinberger Belém Sampaio-Marques Paula Ludovico William C. Burhans 《Cell cycle (Georgetown, Tex.)》2013,12(8):1189-1200
In many organisms, attenuation of growth signaling by caloric restriction or mutational inactivation of growth signaling pathways extends lifespan and protects against cancer and other age-related diseases. The focus of many efforts to understand these effects has been on the induction of oxidative stress defenses that inhibit cellular senescence and cell death. Here we show that in the model organism S. cerevisiae, growth signaling induces entry of cells in stationary phase into S phase in parallel with loss of reproductive capacity, which is enhanced by elevated concentrations of glucose. Overexpression of RNR1 encoding a ribonucleotide reductase subunit required for the synthesis of deoxynucleotide triphosphates and DNA replication suppresses the accelerated loss of reproductive capacity of cells cultured in high glucose. The reduced reproductive capacity of these cells is also suppressed by excess threonine, which buffers dNTP pools when ribonucleotide reductase activity is limiting. Caloric restriction or inactivation of the AKT homolog Sch9p inhibits senescence and death in stationary phase cells caused by the DNA replication inhibitor hydroxyurea or by inactivation of the DNA replication and repair proteins Sgs1p or Rad27p. Inhibition of DNA replication stress represents a novel mechanism by which caloric restriction promotes longevity in S. cerevisiae. A similar mechanism may promote longevity and inhibit cancer and other age-related diseases in humans. 相似文献
103.
Leaf structure and defence control litter decomposition rate across species and life forms in regional floras on two continents 总被引:17,自引:2,他引:17
104.
《Cell cycle (Georgetown, Tex.)》2013,12(20):3876-3886
DJ-1 (or PARK-7) is a multifunctional protein implicated in numerous pathologies including cancer, sterility and Parkinson disease (PD). The popular genetic model Drosophila melanogaster has two orthologs, dj-1: α and β. Dysfunction of dj-1β strongly impairs fly mobility in an age-dependent manner. In this study, we analyze in detail the molecular mechanism underlying the dj-1β mutant phenotype. Mitochondrial hydrogen peroxide production, but not superoxide production, was increased in mutant flies. An increase in peroxide leak from mitochondria causes oxidative damage elsewhere and explains the strong reduction in mobility caused by dj-1β mutation. However, at the same time, increased levels of hydrogen peroxide activated a pro-survival program characterized by (1) an alteration in insulin-like signaling, (2) an increase in mitochondrial biogenesis and (3) an increase in the de-acetylase activity of sirtuins. The activation of this pro-survival program was associated with increased longevity under conditions of moderate oxidative stress. Additionally, the dj-1β mutation unexpectedly accelerated development, a phenotype not previously associated with this mutation. Our results reveal an important role of dj-1β in oxidative stress handling, insulin-like signaling and development in Drosophila melanogaster. 相似文献
105.
Bethan Britt-Compton 《FEBS letters》2009,583(18):3076-89
Short telomeres have been shown to be preferentially elongated in both yeast and mouse models. We examined this in human cells, by utilising cells with large allelic telomere length differentials and observing the relative rates of elongation following the expression of hTERT. We observed that short telomeres are gradually elongated in the first 26 PDs of growth, whereas the longer telomeres displayed limited elongation in this period. Telomeres coalesced at similar lengths irrespective of their length prior to the expression of hTERT. These data indicate that short telomeres are marked for gradual elongation to a cell strain specific length threshold. 相似文献
106.
Maria Razzoli Kewir Nyuyki‐Dufe Allison Gurney Connor Erickson Jacob McCallum Nicholas Spielman Marta Marzullo Jessica Patricelli Morito Kurata Emily A. Pope Chadi Touma Rupert Palme David A. Largaespada Alessandro Bartolomucci 《Aging cell》2018,17(4)
Stress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality. However, this association is not mechanistically understood nor has its causation been explored in animal models thus far. Recently, cellular senescence has been suggested as a potential mechanism linking lifelong stress to age‐related diseases and shorter life expectancy in humans. Here, we established a causal role for lifelong social stress on shortening lifespan and increasing the risk of cardiovascular disease in mice. Specifically, we developed a lifelong chronic psychosocial stress model in which male mouse aggressive behavior is used to study the impact of negative social confrontations on healthspan and lifespan. C57BL/6J mice identified through unbiased cluster analysis for receiving high while exhibiting low aggression, or identified as subordinate based on an ethologic criterion, had lower median and maximal lifespan, and developed earlier onset of several organ pathologies in the presence of a cellular senescence signature. Critically, subordinate mice developed spontaneous early‐stage atherosclerotic lesions of the aortic sinuses characterized by significant immune cells infiltration and sporadic rupture and calcification, none of which was found in dominant subjects. In conclusion, we present here the first rodent model to study and mechanistically dissect the impact of chronic stress on lifespan and disease of aging. These data highlight a conserved role for social stress and low social status on shortening lifespan and increasing the risk of cardiovascular disease in mammals and identify a potential mechanistic link for this complex phenomenon. 相似文献
107.
Lifelong reduction in complex IV induces tissue‐specific metabolic effects but does not reduce lifespan or healthspan in mice
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Sathyaseelan S. Deepa Gavin Pharaoh Michael Kinter Vivian Diaz Wilson C. Fok Kaitlyn Riddle Daniel Pulliam Shauna Hill Kathleen E. Fischer Vanessa Soto Constantin Georgescu Jonathan D. Wren Carlo Viscomi Arlan Richardson Holly Van Remmen 《Aging cell》2018,17(4)
Loss of SURF1, a Complex IV assembly protein, was reported to increase lifespan in mice despite dramatically lower cytochrome oxidase (COX) activity. Consistent with this, our previous studies found advantageous changes in metabolism (reduced adiposity, increased insulin sensitivity, and mitochondrial biogenesis) in Surf1?/? mice. The lack of deleterious phenotypes in Surf1?/? mice is contrary to the hypothesis that mitochondrial dysfunction contributes to aging. We found only a modest (nonsignificant) extension of lifespan (7% median, 16% maximum) and no change in healthspan indices in Surf1?/? vs. Surf1+/+ mice despite substantial decreases in COX activity (22%–87% across tissues). Dietary restriction (DR) increased median lifespan in both Surf1+/+ and Surf1?/? mice (36% and 19%, respectively). We measured gene expression, metabolites, and targeted expression of key metabolic proteins in adipose tissue, liver, and brain in Surf1+/+ and Surf1?/? mice. Gene expression was differentially regulated in a tissue‐specific manner. Many proteins and metabolites are downregulated in Surf1?/? adipose tissue and reversed by DR, while in brain, most metabolites that changed were elevated in Surf1?/? mice. Finally, mitochondrial unfolded protein response (UPRmt)‐associated proteins were not uniformly altered by age or genotype, suggesting the UPRmt is not a key player in aging or in response to reduced COX activity. While the changes in gene expression and metabolism may represent compensatory responses to mitochondrial stress, the important outcome of this study is that lifespan and healthspan are not compromised in Surf1?/? mice, suggesting that not all mitochondrial deficiencies are a critical determinant of lifespan. 相似文献
108.
109.
Deciduous larches, Larix spp., and evergreen pines, Pinus spp., are sympatric Pinaceae conifers. Adjacent monocultures of 10-year-old Larix decidua Mill. and Pinus resinosa Ait. were subjected to single-season artificial defoliation by clipping from 0% to 99% of each needle. Survival, above-ground
productivity, and architecture were measured for 36 months. P. resinosa and L. decidua exhibited differential relationships with defoliation intensity and recovery time. Two months after treatment, defoliation
reduced larch height growth but had no effect on radial growth. By contrast, P. resinosa stem radial growth was reduced immediately, but height growth was not decreased until the following year. Pine leader growth
and above-ground biomass following 66% defoliation never recovered to control values or 33% defoliated pines. Conversely,
defoliated larch quickly recovered from an initial growth loss to eliminate all treatment effects on biomass. The plasticity
in architectural response found in larch, but not pine, might partially account for defoliation tolerance. Both P. resinosa and L. decidua exhibited non-linear responses to defoliation. These patterns may be caused partially by the uneven distribution of nutrients
within needles, rather than a simple function of leaf area lost to defoliators. Concentrations of 13 nutrients in P. resinosa were highest either in the mid- (Ca, Mg, S, Zn, B, Mn, Fe, Al and Na) or basal- (N, P, K, and Cu) section. The relatively
low nutrient content in needle tips may contribute to similar biomass productivity between trees defoliated 33% and controls.
Removal of needle mid-sections significantly reduced whole-plant productivity. In contrast, L. decidua nutrients are concentrated in the distal sections. Nutrient concentrations were generally highest in larch. Our results agree
with an emergent prediction of the carbon/nutrient balance theory that defoliation more severely reduces growth of evergreen
than deciduous species. These results are discussed within the physiological, ecological and evolutionary context of allocation
theory, with implications for natural resource management and plant-insect interaction theory.
Received: 6 April 1995 / Accepted: 29 August 1995 相似文献
110.
Phenotypes optimized for early‐life reproduction exhibit faster somatic deterioration with age,revealing a latent cost of high condition
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High condition enables individuals to express a phenotype with greater reproductive potential. However, life‐history theory predicts that reproduction will trade off with somatic maintenance and viability, and several studies have reported faster age‐related decline in performance in high‐condition individuals, suggesting that high condition in early life is associated with accelerated somatic deterioration. This trade‐off may be especially pronounced in males, which often express condition‐dependent secondary sexual traits that can impose viability costs during development and through damage‐inflicting adult sexual behaviours. To test this prediction, we reared larvae of the neriid fly Telostylinus angusticollis on diets of varying nutrient content and quantified somatic deterioration in solitary males, males housed in all‐male or mixed‐sex groups and immobilized males subjected to mechanical stress. We found that males reared on a nutrient‐rich larval diet (high‐condition males) suffered a higher rate of somatic deterioration with age, particularly when housed in groups. Perhaps as a result of accelerated somatic deterioration, high‐condition males did not outlive low‐condition males. In addition, high‐condition males housed in all‐male groups experienced a greater reduction in escape response with age than males housed in mixed‐sex groups, suggesting that male–male combat promotes somatic deterioration. However, even when immobilized, high‐condition males were still found to be more susceptible to somatic damage than low‐condition males. Our findings suggest that a high‐condition male phenotype is more prone to somatic damage, both as a result of associated behaviours such as combat, and because of the inherent fragility of the high‐condition body. 相似文献