Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans

The beneficial effects of polyphenol compounds in fruits and vegetables are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary polyphenols are beneficial in whole animals, particularly with respect to aging. To address this question, we examined the effects of blueberry polyphenols on lifespan and aging of the nematode, Caenorhabditis elegans, a useful organism for such a study. We report that a complex mixture of blueberry polyphenols increased lifespan and slowed aging-related declines in C. elegans. We also found that these benefits did not just reflect antioxidant activity in these compounds. For instance, blueberry treatment increased survival during acute heat stress, but was not protective against acute oxidative stress. The blueberry extract consists of three major fractions that all contain antioxidant activity. However, only one fraction, enriched in proanthocyanidin compounds, increased C. elegans lifespan and thermotolerance. To further determine how polyphenols prolonged C. elegans lifespan, we analyzed the genetic requirements for these effects. Prolonged lifespan from this treatment required the presence of a CaMKII pathway that mediates osmotic stress resistance, though not other pathways that affect stress resistance and longevity. In conclusion, polyphenolic compounds in blueberries had robust and reproducible benefits during aging that were separable from antioxidant effects.     

Regulation of chronological aging in Schizosaccharomyces pombe by the protein kinases Pka1 and Sck2

Budding yeast shows a progressive decline in viability after entering stationary phase, a phenomenon known as chronological aging. We show here that the fission yeast Schizosaccharomyces pombe also undergoes chronological aging and that the process is regulated by genes controlling two related nutrient signalling pathways. The first pathway includes the serine/threonine cAMP-activated protein kinase Pka1 and the second pathway comprises the serine/threonine kinase Sck2, a homologue of Saccharomyces cerevisiae SCH9. A double mutant for pka1 and sck2 displayed an additive effect on prolonging the fission yeast lifespan, suggesting that these genes regulate related but independent pathways. These long-lived mutants also accumulated less reactive oxygen species and had a delayed initiation of apoptosis compared with wild-type cells. We also found that strains carrying pka1 deletion but not those with sck2 deletion gained resistance to oxidative stress due to exposure to H(2)O(2) or menadione. On the other hand, the additional increase in lifespan shown by the Deltapka1Deltasck2 double-mutant strain correlated with an increased resistance to both oxidative stress and heat shock. These results underscore the importance of nutrient signalling pathways and reactive oxygen species on organismal lifespan and establish S. pombe as a new model organism to study the molecular mechanisms underlying aging.     

Lifespan extension in Caenorhabditis elegans by complete removal of food

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. These findings represent the first report in any organism of lifespan extension in response to prolonged starvation. Removal of bacterial food increases lifespan to a greater extent than partial reduction of food through a mechanism that is distinct from insulin/IGF-like signaling and the Sir2-family deacetylase, SIR-2.1. Removal of bacterial food also increases lifespan when initiated in postreproductive adults, suggesting that dietary restriction started during middle age can result in a substantial longevity benefit that is independent of reproduction.     

Impaired mitophagosome–lysosome fusion mediates olanzapine-induced aging

The lifespan of schizophrenia patients is significantly shorter than the general population. Olanzapine is one of the most commonly used antipsychotic drugs (APDs) for treating patients with psychosis, including schizophrenia and bipolar disorder. Despite their effectiveness in treating positive and negative symptoms, prolonged exposure to APDs may lead to accelerated aging and cognitive decline, among other side effects. Here we report that dysfunctional mitophagy is a fundamental mechanism underlying accelerated aging induced by olanzapine, using in vitro and in vivo (Caenorhabditis elegans) models. We showed that the aberrant mitophagy caused by olanzapine was via blocking mitophagosome–lysosome fusion. Furthermore, olanzapine can induce mitochondrial damage and hyperfragmentation of the mitochondrial network. The mitophagosome–lysosome fusion in olanzapine-induced aging models can be restored by a mitophagy inducer, urolithin A, which alleviates defective mitophagy, mitochondrial damage, and fragmentation of the mitochondrial network. Moreover, the mitophagy inducer ameliorated behavioral changes induced by olanzapine, including shortened lifespan, and impaired health span, learning, and memory. These data indicate that olanzapine impairs mitophagy, leading to the shortened lifespan, impaired health span, and cognitive deficits. Furthermore, this study suggests the potential application of mitophagy inducers as therapeutic strategies to reverse APD-induced adverse effects associated with accelerated aging.     

The effect of defoliation intensity and history on photosynthesis, growth and carbon reserves of two conifers with contrasting leaf lifespans and growth habits

The effects of partial defoliation on photosynthesis, whole-seedling carbon allocation, partitioning and growth were studied for two species with contrasting foliar traits. Field-grown seedlings of deciduous Japanese larch ( Larix leptolepis ) and evergreen red pine ( Pinus resinosa ) were defoliated by hand in early summer for 2 consecutive years. In the first year (1990), seedlings were defoliated by removing the distal 0, 25, 50 or 75% of each needle. In the second year (1991), seedlings were defoliated either 0 or 50%, regardless of previous defoliation treatments. Defoliation had little effect on photosynthesis and starch concentration in whole seedlings of either species in the first year. In the second year, photosynthesis increased in both species in response to the 1991 defoliation treatment, and in red pine also increased in response to the 1990 defoliation treatment. Further, in 1991 both larch and pine had decreased whole-seedling total non-structural carbohydrate concentrations in all seedlings that were defoliated at least once over the 2-yr period. This decrease was noted mostly in the starch component of the non-structural carbohydrates, and was similar in both species. In 1991, biomass was similarly decreased in both species in response to 1991 defoliation. Both species showed overcompensation in total and component biomass in seedlings defoliated by 25% in 1990. Overall, the results do not support the widely held belief that evergreen trees are substantially more affected than deciduous trees by defoliation.     

BIASES IN DOLPHIN AGE STRUCTURE DUE TO AGE ESTIMATION TECHNIQUE1

The use of different tooth-preparation techniques resulted in widely different estimates of age in a sample of bottlenose dolphins, Tursiops truncatus. Teeth from 30 animals were prepared using the two most prevalent techniques reported in the literature for this species, unstained sections and decalcified and stained thin sections, and the resulting paired counts of growth layers were compared. Estimates from the two methods were identical or at least placed the specimen in the same age class in only five cases, ranging in age from 2 to 22 yr. Otherwise, the results fell into one of two categories: when the estimates were close (± 3-yr difference, n= 15), counts from unstained sections generally were higher (13 cases, age from unstained sections 2-20 yr); when the counts were more disparate, estimates from stained sections always were higher (6-31 yr difference, n= 10, age from unstained sections 12-27 yr and corresponding ages from stained sections of 27-47). Previous studies of age estimation in known-age bottlenose dolphins indicate that stained sections allow accurate estimates of age and demonstrate that maximum lifespan approaches or exceeds 50 yr. In contrast, the results herein suggest that using unstained sections for age estimation may result in imprecise or biased age-structure data.     

Comparative Analysis of Mammal Genomes Unveils Key Genomic Variability for Human Life Span

The enormous mammal’s lifespan variation is the result of each species’ adaptations to their own biological trade-offs and ecological conditions. Comparative genomics have demonstrated that genomic factors underlying both, species lifespans and longevity of individuals, are in part shared across the tree of life. Here, we compared protein-coding regions across the mammalian phylogeny to detect individual amino acid (AA) changes shared by the most long-lived mammals and genes whose rates of protein evolution correlate with longevity. We discovered a total of 2,737 AA in 2,004 genes that distinguish long- and short-lived mammals, significantly more than expected by chance (P = 0.003). These genes belong to pathways involved in regulating lifespan, such as inflammatory response and hemostasis. Among them, a total 1,157 AA showed a significant association with maximum lifespan in a phylogenetic test. Interestingly, most of the detected AA positions do not vary in extant human populations (81.2%) or have allele frequencies below 1% (99.78%). Consequently, almost none of these putatively important variants could have been detected by genome-wide association studies, suggesting that comparative genomics can be used to complement and enhance interpretation of human genome-wide association studies. Additionally, we identified four more genes whose rate of protein evolution correlated with longevity in mammals. Finally, we show that the human longevity-associated proteins are significantly more stable than the orthologous proteins from short-lived mammals, strongly suggesting that general protein stability is linked to increased lifespan.     

The Cost of Reproduction in the Rotifer Brachionus calyciflorus Pallas

A study of lifespan, fecundity, and reproductive schedules was carried out with the rotifer Brachionus calyciflorus under different food concentrations. At high food densities (6.1 to 12.4 μg · ml⁻¹, dry mass) there was an increase in offspring number but the reproductive investment remained constantly. This was possible because Brachionus calyciflorus invested a smaller amount of energy one egg volume being able to increase offspring number. Although egg volume was reduced, this was compensated by the greater amount of energy available to the neonates. The length of the prereproductive period remained constant throughout this range of food concentrations. Within this range a reduction in lifespan was observed. This, however, was not due to a total higher reproductive investment, but to an increased offspring rate production resulting in a shortening of the reproductive period. The length of the post-reproductive period was not different at all food concentrations.     

Molecular Characterization of Mn-superoxide Dismutase and Gene Expression Studies in Dietary Restricted <Emphasis Type="Italic">Brachionus plicatilis</Emphasis> Rotifers

Superoxide dismutases (SODs) promote a conversion of harmful reactive oxygen species (ROS) to relatively moderate forms, resulting in the extension of lifespan in the nematode Caenorhabditis elegans under caloric restriction. The lifespan of the rotifer Brachionus plicatilis is also markedly extended by caloric restriction. We, therefore, cloned cDNA encoding SOD activated with Mn (Mn SOD) from B. plicatilis and examined its expression pattern in rotifers raised with energy restricted diet. The full length deduced amino acid sequence of the rotifer Mn SOD showed 61% identity with the C. elegans ortholog. Four amino acid residues that are essential to the binding of this enzyme to Mn were conserved in the rotifer Mn SOD. Subsequently we examined the mRNA expression patterns of Mn SOD using highly sensitive quantitative real-time PCR for various rotifer populations that are likely to differ in their lifespans in experiments on calorie restricted diets. The accumulated mRNA levels of Mn SOD were found to increase in supposedly long-lived rotifers. These results suggest that Mn SOD is possibly related to the aging of B. plicatilis.     

Mitochondrial medicine: neuroprotection and life extension by the new amphiphilic nitrone LPBNAH acting as a highly potent antioxidant agent

The search for effective treatments that prevent oxidative stress associated with premature ageing and neurodegenerative diseases is an important area of neurochemical research. As age- and disease-related oxidative stress is frequently associated with mitochondrial dysfunction, amphiphilic antioxidant agents of high stability and selectivity that target these organelles can provide on-site protection. Such an amphiphilic nitrone protected human neuroblastoma cells at low micromolar concentrations against oxidative damage and death induced by exposure to the beta-amyloid peptide, hydrogen peroxide and 3-hydroxykynurenine. Daily administration of the antioxidant at a concentration of only 5 mum significantly increased the lifespan of the individually cultured rotifer Philodina acuticornis odiosa Milne. This compound is unique in its exceptional anti-ageing efficacy, being one order of magnitude more potent than any other compound previously tested on rotifers. The nitrone protected these aquatic animals against the lethal toxicity of hydrogen peroxide and doxorubicin and greatly enhanced their survival when co-administered with these oxidotoxins. These findings indicate that amphiphilic antioxidants have a great potential as neuroprotective agents in preventing the death of cells and organisms exposed to enhanced oxidative stress and damage.