Sex differences in telomeres and lifespan

Males and females often age at different rates resulting in longevity 'gender gaps', where one sex outlives the other. Why the sexes have different lifespans is an age-old question, still fiercely debated today. One cellular process related to lifespan, which is known to differ according to sex, is the rate at which the protective telomere chromosome caps are lost. In humans, men have shorter lifespans and greater telomere shortening. This has led to speculation in the medical literature that sex-specific telomere shortening is one cause of sex-specific mortality. However, telomere shortening may be a cause for and/or a consequence of the processes that govern survival, and to infer general principles from single-taxon studies may be misleading. Here, we review recent work on telomeres in a variety of animal taxa, including those with reverse sexual lifespan dimorphism (i.e., where males live longer), to establish whether sex-specific survival is generally associated with sex differences in telomere dynamics. By doing this, we attempt to tease apart the potential underlying causes for sex differences in telomere lengths in humans and highlight targets for future research across all taxa.     

Antioxidants and cataract

Abstract

The major causes for cataract formation are free radicals, and these free radicals are neutralized by the presence of endogenous antioxidants in the eye. Using xenobiotics, it has been confirmed that free radicals mediate the formation of cataract. Two cataract model-selenite model and the diabetic cataract model-have been developed to study the pathophysiology of cataract formation due to free radicals and the role of antioxidants during the process of cataractogenesis. This review focuses on natural compounds with antioxidant properties that could actually be applied as an interventional strategy on a large scale and are also relatively inexpensive. A brief overview of plants with antioxidant properties that in addition possess potential anti-cataract properties has been discussed. In addition to plants, three natural compounds (curcumin, vitamin C and vitamin E), on which a lot of data exist showing anti-cataract and antioxidant activities, have also been discussed. These antioxidants can be supplemented in the diet for a better defence against free radicals. Studies on vitamin C and vitamin E have proved that they are capable of preventing lipid peroxidation, thereby preventing the generation of free radicals, but their efficacy as anti-cataract agent is questionable. Unlike vitamins C and E, curcumin is well established as an anti-cataract agent, but the issue of curcumin bioavailability is yet to be addressed. Nanotechnology proves to be a promising area in increasing the curcumin bioavailability, but still a lot more research needs to be done before the use of curcumin as an effective anti-cataract agent for humans.     

Antioxidants in patients receiving total parenteral nutrition after gastrointestinal cancer surgery

Total parenteral nutrition (TPN) is essential for patients with postoperative impairing gastrointestinal function who are unable to receive and absorb oral/enteral feeding for at least 7 days. Oxidative stress plays a major role in the ethiopathogenesis of cancers. In this study, total antioxidant status (TAS), glutathione peroxidase (GPx), superoxide dismutase, malondialdehyde and ascorbic acid were studied in patients operated because of small intestine, colorectal or pancreatic cancer and subsequently receiving TPN in comparison with patients receiving standard nutrition after the operation. TAS level and GPx activity were decreased in patients with small intestine cancer but did not differ in patients with colorectal and pancreatic cancer before and after surgery. In all patient groups receiving TPN, superoxide dismutase activity after the surgery was kept at the same level as before. On the fifth day after the surgery, malondialdehyde concentration in each group was restored to the value observed before surgery. On the fifth day of TPN treatment, ascorbic acid concentration was increased in every group of patients. TPN applied during the postoperative period alleviates oxidative stress resulting from surgery. In the case of small intestine cancer, the addition of vitamins and antioxidants to the nutrition mixture seems to result in depletion of antioxidant enzymes' activities.     

Influence of Antioxidants on the Peroxidative Swelling of Mitochondria in vitro

To clarify the role of prooxidative processes during in vitro swelling of freshly isolated rat liver mitochondria, the influence of different antioxidants and free-radical scavengers was tested. Ascorbate below 10 mmol/L without externally added Fe²⁺ acted as a prooxidant and enhanced swelling. Higher concentrations in the presence of Fe²⁺ showed antioxidant properties and a decrease in swelling and lipid peroxidation. Swelling was abolished by -tocopherol and reduced to 50% by butylated hydroxytoluene. Glutathione supplementation decreased both swelling and lipid peroxidation. Oxidized glutathione caused swelling without any effect on peroxidation. Hydrogen peroxide, cumene hydroperoxide and t-butyl hydroperoxide caused progressive decreases in glutathione and reduced niacinamide coenzyme levels, suggesting prooxidative changes. Dithiothreitol was found to abolish this effect. Thus, antioxidants reverse superoxide-induced mito chondrial swelling and lipid peroxidation in vitro.     

The association between stressors and telomeres in non‐human vertebrates: a meta‐analysis

Animal response to stressors such as harsh environmental conditions and demanding biological processes requires energy generated through increased mitochondrial activity. This results in the production of reactive oxygen species (ROS). In vitro and some in vivo studies suggest that oxidative damage of DNA caused by ROS is responsible for telomere shortening. Since telomere length is correlated with survival in many vertebrates, telomere loss is hypothesised to trigger cellular ageing and/ or to reflect the harshness of the environment an individual has experienced. To improve our understanding of stress‐induced telomere dynamics in non‐human vertebrates, we analysed 109 relevant studies in a meta‐analytical framework. Overall, the exposure to possible stressors was associated with shorter telomeres or higher telomere shortening rate (average effect size = ?0.16 ± 0.03). This relationship was consistent for all phylogenetic classes and for all a priori‐selected stressor categories. It was stronger in the case of pathogen infection, competition, reproductive effort and high activity level, which emphasises their importance in explaining intraspecific telomere length variability and, potentially, lifespan variability. Interestingly, the association between stressor exposure and telomeres in one hand, and oxidative stress in the other hand, covaried, suggesting the implication of oxidative stress in telomere dynamics.     

Relationships among oxidative status,breeding conditions and life‐history traits in free‐living Great Tits Parus major and Common Starlings Sturnus vulgaris

The interest shown by ecologists in antioxidants and oxidative stress as potential modulators of life‐history trade‐offs has expanded greatly in recent years. However, we still know very little about natural variation in oxidative damage and antioxidant capacity in free‐living animals. In this study, we describe the natural variation in three components of oxidative balance in nestlings and breeding females in free‐living Great Tits Parus major and Common Starlings Sturnus vulgaris in central Italy, and relate these to breeding conditions and life‐history traits. Our results suggest that there are associations among oxidative physiology, reproductive activity, growth pattern and season in wild birds, but that the nature of these associations might be species‐specific rather than general across species.     

Selection of antioxidants against ovarian oxidative stress in mouse model

Oxidative stress (OS) plays an important role in the process of ovarian granulosa cell apoptosis and follicular atresia. The aim of this study was to select antioxidant against OS in ovary tissue. Firstly, we chose the six antioxidants and analyzed the reactive oxygen species (ROS) level in the ovary tissue. The results showed that proanthocyanidins, gallic acid, curcumin, and carotene decrease the ROS level compared with control group. We further demonstrated that both proanthocyanidins and gallic acid increase the antioxidant enzymes activity. Moreover, change in the ROS level was not observed in proanthocyanidins and gallic acid group of brain, liver, spleen, and kidney tissues. Finally, we found that proanthocyanidins and gallic acid inhibit pro‐apoptotic genes expression in granulosa cells. Taken together, proanthocyanidins and gallic acid may be the most acceptable and optimal antioxidants specifically against ovarian OS and also may be involved in the inhibition of granulosa cells apoptosis in mouse ovary.     

外源水杨酸对高温胁迫下葡萄几种抗氧化酶活性和抗氧化物含量的影响

本文以二年生‘克瑞森’无核葡萄为材料,探明外源水杨酸（SA）对高温胁迫下葡萄体内几种酶活性和抗氧化物质含量的影响及其在抗高温胁迫中的作用。实验结果表明,与对照相比,外源SA可以促进高温胁迫下葡萄叶片内ASA和GSH含量的积累,维持较高的APX、GR、SOD、POD和CAT活性。外源SA可能通过提高高温胁迫下葡萄体内抗氧化水平,削弱了高温胁迫对葡萄植株的氧化胁迫伤害作用。     

Climate change and ageing in ectotherms

Human activity is changing climatic conditions at an unprecedented rate. The impact of these changes may be especially acute on ectotherms since they have limited capacities to use metabolic heat to maintain their body temperature. An increase in temperature is likely to increase the growth rate of ectothermic animals, and may also induce thermal stress via increased exposure to heat waves. Fast growth and thermal stress are metabolically demanding, and both factors can increase oxidative damage to essential biomolecules, accelerating the rate of ageing. Here, we explore the potential impact of global warming on ectotherm ageing through its effects on reactive oxygen species production, oxidative damage, and telomere shortening, at the individual and intergenerational levels. Most evidence derives primarily from vertebrates, although the concepts are broadly applicable to invertebrates. We also discuss candidate mechanisms that could buffer ectotherms from the potentially negative consequences of climate change on ageing. Finally, we suggest some potential applications of the study of ageing mechanisms for the implementation of conservation actions. We find a clear need for more ecological, biogeographical, and evolutionary studies on the impact of global climate change on patterns of ageing rates in wild populations of ectotherms facing warming conditions. Understanding the impact of warming on animal life histories, and on ageing in particular, needs to be incorporated into the design of measures to preserve biodiversity to improve their effectiveness.     

Telomeric replication stress: the beginning and the end for alternative lengthening of telomeres cancers

Telomeres are nucleoprotein structures that cap the ends of linear chromosomes. Telomeric DNA comprises terminal tracts of G-rich tandem repeats, which are inherently difficult for the replication machinery to navigate. Structural aberrations that promote activation of the alternative lengthening of telomeres (ALT) pathway of telomere maintenance exacerbate replication stress at ALT telomeres, driving fork stalling and fork collapse. This form of telomeric DNA damage perpetuates recombination-mediated repair pathways and break-induced telomere synthesis. The relationship between replication stress and DNA repair is tightly coordinated for the purpose of regulating telomere length in ALT cells, but has been shown to be experimentally manipulatable. This raises the intriguing possibility that induction of replication stress can be used as a means to cause toxic levels of DNA damage at ALT telomeres, thereby selectively disrupting the viability of ALT cancers.     

Crop Improvement and Abiotic Stress Tolerance Promoted by Moringa Leaf Extract

Moringa leaf extract (MLE) has been shown to promote beneficial outcomes in animals and plants. It is rich in amino acids, antioxidants, phytohormones, minerals, and many other bioactive compounds with nutritional and growth-promoting potential. Recent reports indicated that MLE improved abiotic stress tolerance in plants. Our understanding of the mechanisms underlying MLE-mediated abiotic stress tolerance remains limited. This review summarizes the existing literature on the role of MLE in promoting plant abiotic stress acclimation processes. MLE is applied to plants in a variety of ways, including foliar spray, rooting media, and seed priming. Exogenous application of MLE promoted crop plant growth, photosynthesis, and yield under both nonstress and abiotic stress conditions. MLE treatment reduced the severity of osmotic and oxidative stress in plants by regulating osmolyte accumulation, antioxidant synthesis, and secondary metabolites. MLE also improves mineral homeostasis in the presence of abiotic stress. Overall, this review describes the potential mechanisms underpinning MLE-mediated stress tolerance.     

Antioxidants, showy males and sperm quality

The fertility of males sometimes correlates with their ornamental display, but we do not have a mechanistic explanation to universally link these traits. We suggest that both sperm quality (fertility; integrity of DNA), and the substrates responsible for male ornamentation, may be vulnerable to free radical attack, which can be mitigated by antioxidants. Support for these ideas is at present weak, and requires validation in ecological contexts. We hypothesize that a link between ornamentation and sperm quality could arise if antioxidants are in limited supply, and the showiest males may be preferred because they are most likely to be fertile, or to provide sperm with undamaged genotypes that could give rise to fit offspring.     

Antioxidants protect the yeast Saccharomyces cerevisiae against hypertonic stress

Yeast (Saccharomyces cerevisiae) mutants lacking CuZnSOD have been reported to be hypersensitive to hypertonic media and to show increased oxidative damage. This study demonstrates that hypertonic medium (containing 0.8?M NaCl) increases the generation of superoxide and other reactive species in yeast cells. Other sequelae of exposure to hypertonic medium include oxidation of cellular low-molecular weight thiols and decrease in total antioxidant capacity of cellular extracts. Δsod1 mutant is more sensitive than a wild-type strain to colony growth inhibition on a hypertonic medium. Anaerobic conditions, ascorbate, glutathione, cysteine and dithiothreitol are able to ameliorate this growth inhibition but a range of other antioxidants does not protect. The protective ability of the antioxidants does not correlate with the rate of their reactions with superoxide but seems to be conditioned by low redox potential for one-electron oxidation of free radicals of the antioxidants. It suggests that repair of low-redox potential targets rather than prevention of their damage by superoxide is important in the antioxidant protection against oxidative stress induced by hypertonic conditions.     

HipHop interacts with HOAP and HP1 to protect Drosophila telomeres in a sequence‐independent manner

Telomeres prevent chromosome ends from being repaired as double‐strand breaks (DSBs). Telomere identity in Drosophila is determined epigenetically with no sequence either necessary or sufficient. To better understand this sequence‐independent capping mechanism, we isolated proteins that interact with the HP1/ORC‐associated protein (HOAP) capping protein, and identified HipHop as a subunit of the complex. Loss of one protein destabilizes the other and renders telomeres susceptible to fusion. Both HipHop and HOAP are enriched at telomeres, where they also interact with the conserved HP1 protein. We developed a model telomere lacking repetitive sequences to study the distribution of HipHop, HOAP and HP1 using chromatin immunoprecipitation (ChIP). We discovered that they occupy a broad region >10 kb from the chromosome end and their binding is independent of the underlying DNA sequence. HipHop and HOAP are both rapidly evolving proteins yet their telomeric deposition is under the control of the conserved ATM and Mre11–Rad50–Nbs (MRN) proteins that modulate DNA structures at telomeres and at DSBs. Our characterization of HipHop and HOAP reveals functional analogies between the Drosophila proteins and subunits of the yeast and mammalian capping complexes, implicating conservation in epigenetic capping mechanisms.     

A mechanistic understanding of ageing revealed by studying the young

A main focus within biomedical research is to understand how adverse environmental conditions experienced during early development affects lifelong health (Barker 1992). Within this context, extensive research in rodent models and humans has shown that intrauterine growth retardation (IUGR) caused by nutrient restriction during early development is often followed by post-natal 'catch-up' growth when access to food resources improves. However, this accelerated growth rate seems to come at a cost, as metabolic and endocrine processes that are programmed during this time cause later-life onset of diseases such as obesity, insulin resistance and cardiovascular disease (reviewed in Crespi & Denver 2005). In this issue Molecular Ecology, Geiger et al. (2012) asked what are the costs of catch-up growth in nutrient-restricted king penguin chicks (Fig. 1) by measuring lengths of telomeres, the protective DNA sequences at the end of chromosomes, before and after catch-up growth, as the amount and rate of telomere sequence loss over time has been associated with reduced lifespan in both model and nonmodel organisms (see reviews of Costantini et al. 2010; Haussmann & Marchetto 2010). Geiger et al. (2011) found that chicks entering the post-winter growth season at a smaller size exhibited increased growth rates (i.e. catch-up growth) at the cost of increased oxidative stress and reduced telomere lengths compared with the chicks entering the growth period at a larger size. Furthermore, chicks that did not survive had drastically shorter telomere lengths and reduced antioxidant capacities at the beginning of the growth period than all other chicks, thereby directly associating telomere length to mortality. These results suggest that while catch-up growth allows smaller chicks to head off into the world on equal footing with chicks that hatched at a larger size, it likely comes at the cost of a shortened lifespan. Thus, this study provides a mechanism that supports the antagonistic pleiotropy theory of senescence (Promislow 2004).     

Antioxidative activity of thiophane [bis(3-(3,5-di-tret-butyl-4-hydroxyphenyl)propyl)sulfide]

The antioxidant activity, mutagenicity, and genotoxicity of bis(3-(3,5-di-tret-butyl-4-hydroxyphenyl)propyl)sulfide (thiophane) were studied using bacterial tests. The results of both an Ames test and SOS chromotest, as well as those studying the survival of E. coli cells deficient in enzymes responsible for the repair of DNA oxidative damage, testify to the fact that thiophane is not mutagenic and genotoxic, and it protects Salmonella typhimurium cells better than the well-known antioxidant trolox.     

Oxidative stress and antioxidant content in Chlorella vulgaris after exposure to ultraviolet-B radiation

Growth of Chlorella vulgaris was measured in cultures irradiated with 0, 0.8, 2.0 and 4.4 kJ m² UV-B. Growth expressed as chlorophyll content, declined significantly with increased UV-B dose. Ultraviolet-B irradiated cultures in log phase of growth showed a 284% increase in oxygen radical generation and a 145% increase in lipid peroxidation compared with unirradiated cultures, whereas cultures in the stationary growth phase showed no significant changes in these parameters. The activities of superoxide dismutase and catalase increased by 40 and 500%, respectively, after exposure to a UV-B dose of 4.4 kJ m⁻². Contents of the lipophilic antioxidants α-tocopherol and β-carotene increased by 180 and 63 amol cell⁻¹ respectively, between log and stationary phases in unirradiated cultures; but in UV-B-irradiated cultures these increases were significantly depressed. Photoreducing capacities of chloroplasts were decreased following UV-B irradiation of both isolated chloroplasts and those isolated from irradiated algae. Cells exposed to UV-B exhibited increased size and starch accumulation. These results suggest that oxidative stress conditions related to UV-B exposure trigger an antioxidant response that includes an increase in the activity of the antioxidant enzymes (superoxide dismutase and catalase).     

Cyclic oxidation and reduction of protein methionine residues is an important antioxidant mechanism

Almost all forms of reactive oxygen species (ROS) oxidize methionine residues of proteins to a mixture of the R- and S-isomers of methionine sulfoxide. Because organisms contain methionine sulfoxide reductases (Msr's) that can catalyze the thioredoxin-dependent reduction of the sulfoxides back to methionine, it was proposed that the cyclic oxidation/reduction of methionine residues might serve as antioxidants to scavenge ROS, and also to facilitate the regulation of critical enzyme activities. We summarize here results of studies showing that organisms possess two different forms of Msr – namely, MsrA that catalyzes reduction of the S-isomer and MsrB that catalyzes the reduction of the R-isomer. Deletion of the msrA gene in mice leads to increased sensitivity to oxidative stress and to a decrease (40%) in the maximum lifespan. This suggests that elimination of both Msr's would have more serious consequences.