A novel assay for replicative lifespan in Saccharomyces cerevisiae

The replicative lifespan of Saccharomyces cerevisiae is determined by both genetic and environmental factors. Many of the same factors determine the lifespan of metazoan animals. The lack of fast and reliable lifespan assays has limited the pace of yeast aging research. In this study we describe a novel strategy for assaying replicative lifespan in yeast, and apply it in a screening of mutants that are resistant to pro-oxidants. The assay reproduces the lifespan-shortening effects of deleting SIR2 and of growth in the presence of paraquat, a pro-oxidant. The lifespan-increasing activity of resveratrol is also reproduced. Compared to current assays, this new strategy promises to significantly increase the possible number of replicative-lifespan determinations.     

The interaction between reproductive lifespan and protandry in seasonal breeders

The timing and duration of reproductive activities are highly variable both at the individual and population level. Understanding how this variation evolved by natural selection is fundamental to understanding many important aspects of an organism's life history, ecology and behaviour. Here, we combine game theoretic principles governing reproductive timing and the evolutionary theory of senescence to study the interaction between protandry (the earlier arrival or emergence of males to breeding areas than females) and senescence in seasonal breeders. Our general model applies to males who are seeking to mate as frequently as possible over a relatively short period, and so is relevant to many organisms including annual insects and semelparous vertebrates. The model predicts that protandry and maximum reproductive lifespans should increase in environments characterized by high survival and by a low competitive cost of maintaining the somatic machinery necessary for survival. In relatively short seasons under these same conditions, seasonal declines in the reproductive lifespans of males of equivalent quality will be evolutionarily stable. However, over a broad range of potential values for daily survival and maintenance cost, reproductive lifespan is expected to be relatively short and constant throughout a large fraction of the season. We applied the model to sockeye (or kokanee) salmon Oncorhynchus nerka and show that pronounced seasonal declines in reproductive lifespan, a distinctive feature of semelparous Oncorhynchus spp., is likely part of a male mating strategy to maximize mating opportunities.     

动物寿命与人类影响

地球上各种生物有机体的寿命是有本质差异的,即使一些大小、形态和生理上大体相似的生物之间也存在着这种差异。早期的研究多集中在探讨基因、热量限制、药物与动物特别是人类寿命的相关性上,而环境因素以及日益加剧的人类活动对动物寿命的影响则很少被涉及。目前,越来越多的证据显示,人类以倍人类活动对动物的寿命有着直接或间接的影响。正面的影响可以从近年来诸如自然保护区的建立等保护措施的实施活动中得到体现。然而,由于日益加剧的人类活动造成的自然生境的日益萎缩和片段化所带来的负面影响也是非常明显的,人们不应只关注人类活动如何导致物种的绝灭,也应研究人类如何改变动物的生存环境、寿命以及动物固有的生命轨迹。介绍了有关动物寿命研究的最新进展,呼吁更多的学者投身到环境因素对动物寿命的影响这一迅速升温的诱人的研究领域中来。植物方面的类似研究也应该尽早启动。     

Life history and morphological plasticity of the soybean aphid,Aphis glycines

The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is a pest of soybean, Glycine max (L.) Merr. (Fabaceae), from eastern Asia that was first reported in North America in 2000. The influence of temperature on plasticity of life history and morphological traits of the soybean aphid has not been tested despite observable differences in population growth and morphology among isolates in laboratory colonies. Therefore, we used three isolates of the aphid to test whether lifespan, growth rate, fecundity, and morphology were plastic at 16, 24, and 28 °C. Population size of the aphid was influenced by temperature, probably because two reproductive traits, maximum number of offspring in 1 day and total fecundity, were plastic and increased in successive generations at 24 °C. All morphological traits were plastic, including lengths of body parts, number of antennal segments and caudal hairs, and color of siphunculi and body, and they were differentially influenced by isolate and temperature. Knowledge about the life history and morphology of the soybean aphid may help identify its capacity for phenotypic plasticity in heterogeneous temperatures and identify how temperature influences its survival, population growth, and diversity.     

The migration of mitochondrial DNA fragments to the nucleus affects the chronological aging process of Saccharomyces cerevisiae

Migration of fragmented mitochondrial DNA (mtDNA) to the nucleus has been shown to occur in multiple species including yeast, plants, and mammals. Several human diseases, including Pallister–Hall syndrome and mucolipidosis, can be initiated by mtDNA insertion mutagenesis of nuclear DNA. In yeast, we demonstrated that the rate of mtDNA fragments translocating to the nucleus increases during chronological aging. The yeast chronological lifespan (CLS) is determined by the survival of nondividing cell populations. Whereas yeast strains with elevated migration rates of mtDNA fragments to the nucleus showed accelerated chronological aging, strains with decreased mtDNA transfer rates to the nucleus exhibited an extended CLS. Although one of the most popular theories of aging is the free radical theory, migration of mtDNA fragments to the nucleus may also contribute to the chronological aging process by possibly increasing nuclear genomic instability in cells with advanced age.     

High oxidative damage levels in the longest-living rodent, the naked mole-rat

Oxidative stress is reputed to be a significant contributor to the aging process and a key factor affecting species longevity. The tremendous natural variation in maximum species lifespan may be due to interspecific differences in reactive oxygen species generation, antioxidant defenses and/or levels of accrued oxidative damage to cellular macromolecules (such as DNA, lipids and proteins). The present study tests if the exceptional longevity of the longest living (> 28.3 years) rodent species known, the naked mole-rat (NMR, Heterocephalus glaber ), is associated with attenuated levels of oxidative stress. We compare antioxidant defenses (reduced glutathione, GSH), redox status (GSH/GSSG), as well as lipid (malondialdehyde and isoprostanes), DNA (8-OHdG), and protein (carbonyls) oxidation levels in urine and various tissues from both mole-rats and similar-sized mice. Significantly lower GSH and GSH/GSSG in mole-rats indicate poorer antioxidant capacity and a surprisingly more pro-oxidative cellular environment, manifested by 10-fold higher levels of in vivo lipid peroxidation. Furthermore, mole-rats exhibit greater levels of accrued oxidative damage to lipids (twofold), DNA (~two to eight times) and proteins (1.5 to 2-fold) than physiologically age-matched mice, and equal to that of same-aged mice. Given that NMRs live an order of magnitude longer than predicted based on their body size, our findings strongly suggest that mechanisms other than attenuated oxidative stress explain the impressive longevity of this species.     

Exploiting the rodent model for studies on the pharmacology of lifespan extension

The rodent is a particularly valuable model with which to test therapeutic interventions for aging, as rodent physiology is close enough to human physiology to give the findings relevance for human aging, and it is small enough to allow for use of statistically robust sample sizes. There are many rodent models to choose from, with advantages and disadvantages to each. The choice of model system, as well as other experimental design decisions such as diet and housing, is extremely important for the success of lifespan studies. These issues are discussed in this review of the use of the rodent model. The National Institute on Aging (NIA) Interventions Testing Program, which has grappled with all of these issues, is described.     

Studies of Caenorhabditis elegans DAF-2/insulin signaling reveal targets for pharmacological manipulation of lifespan

Much excitement has arisen from the observation that decrements in insulin‐like signaling can dramatically extend lifespan in the nematode, Caenorhabditis elegans, and fruitfly, Drosophila melanogaster. In addition, there are tantalizing hints that the IGF‐I pathway in mice may have similar effects. In addition to dramatic effects on lifespan, invertebrate insulin‐like signaling also promotes changes in stress resistance, metabolism and development. Which, if any, of the various phenotypes of insulin pathway mutants are relevant to longevity? What are the genes that function in collaboration with insulin to prolong lifespan? These questions are at the heart of current research in C. elegans longevity. Two main theories exist as to the mechanism behind insulin's effects on invertebrate longevity. One theory is that insulin programs metabolic parameters that prolong or reduce lifespan. The other theory is that insulin determines the cell's ability to endure oxidative stress from respiration, thereby determining the rate of aging. However, these mechanisms are not mutually exclusive and several studies seem to support a role for both. Here, we review recently published reports investigating the mechanisms behind insulin's dramatic effect on longevity. We also spotlight several C. elegans genes that are now known to interact with insulin signaling to determine lifespan. These insights into pathways affecting invertebrate lifespan may provide a basis for developing strategies for pharmacological manipulation of human lifespan.