Short-term dietary restriction in old mice rejuvenates the aging-induced structural imbalance of gut microbiota In the original publication of the article, the alphabets in figures were published in upper case and mismatched with the figure legends. The corrected figures and figure legends are given in this Correction.

High perceived stress in women is linked to oxidation, inflammation and immunosenescence Abstract Chronic stress situations lead to an impairment of immune response and higher oxidative and inflammatory stress, which are important underlying mechanisms of the ageing process. However, given that the physiological stress response depends on the subjective appraisal of a given stressor, the aim of the study was to investigate the effect that different degrees of perceived stress have, regardless of their type, on immune functions, oxidative and inflammatory stress and ageing rate of women (30–50 years old). For that purpose, a group of 49 women was classified, according to their scores obtained in the perceived stress scale (PSS), into low (n = 23), moderate (n = 14) and high (n = 12) degree of perceived stress. The immune functions studied were: neutrophil and lymphocyte chemotaxis, neutrophil phagocytic capacity, natural killer activity, lymphoproliferation and LPS-stimulated cytokine release. Basal cytokine release was studied as an inflammatory stress marker. Antioxidant (superoxide dismutase, glutathione peroxidase and reductase activities, and reduced glutathione) and oxidant compounds (oxidized glutathione and malondialdehyde) were also investigated in whole blood as markers of oxidative stress. The results show that, in general, women with a moderate or high degree of perceived stress have a worse immune functionality and higher oxidative and inflammatory stress compared to women with low stress perception. In addition, a positive correlation was found between PSS scores and the biological age of each woman (P ≤ 0.001). In conclusion, high levels of perceived stress in women are associated with a higher oxidative and inflammatory stress and immunosenescence, which seem to accelerate their ageing rate.

Hypergravity increases resistance to heat in dFOXO Drosophila melanogaster mutants and can lower FOXO translocation in wild-type males Abstract Severe stresses have deleterious effects, but mild stresses can have beneficial effects called hormetic effects. This study observed survival time of wild-type Drosophila melanogaster flies and dFOXO mutants exposed to 37 °C, a severe stress for flies, after they lived or not for 2 weeks in hypergravity (3 or 5 g), a mild stress with hormetic effects in flies. Hypergravity increased survival time of the mutants, this effect being less observed in wild-type flies. The heat stress increased dFOXO translocation similarly in all gravity groups in a wild-type strain, and hypergravity decreased dFOXO translocation similarly in heat-stressed or not heat-stressed males, no clear effect of the gravity level being observed in females. Because hypergravity increases resistance to heat in dFOXO mutants and the translocation is not tightly dependent on the gravity level, one can conclude that dFOXO does not mediate the effect of hypergravity on resistance to heat. A previous study showed that another mild stress, the cold, can increase survival time at 37 °C of wild-type D. melanogaster flies, but this was not observed in dFOXO mutants. Therefore, two mild stresses, cold and hypergravity, can increase resistance to heat but the pathways mediating this effect are seemingly different, as cold does not increase resistance in dFOXO mutants while hypergravity increases it.

An overview of two decades of diet restriction studies using Drosophila Abstract Dietary restriction (DR) is a potent forerunner in aging studies capable of influencing lifespan and improving health in various model organisms even in their old age. Despite the importance of protein and carbohydrates in the diet (regulation of fecundity and body maintenance respectively), different ratio based combinations of these components has played a major role in lifespan extension studies. In spite of differences existing in dietary protocols across laboratories, diet manipulations have evolved as a major area of research in Drosophila lifespan studies, prominently shedding light on the multi-faceted process over the last two decades. Here, we review various advances and technicalities involved in understanding the DR-mediated lifespan alongside discussing the pros and cons of various existing approaches/diets used across labs. The current review also focuses on the importance of life-stage specific DR implementation and their influence on the life-history traits including lifespan and fecundity, by taking examples of results from different studies comprising diet dilution, calorie restriction, protein restriction, carbohydrate: protein ratios and the modulations in various minor diet components. We thereby intend to gather the major advances made in these fields alongside reviewing the practical implementations that need to be made to get a better view of the DR-mediated lifespan studies.

In silico analysis of human renin gene–gene interactions and neighborhood topologically associated domains suggests breakdown of insulators contribute to ageing-associated diseases Abstract Three-dimensional chromatin architecture and gene–gene interactions impact gene expression. We assembled this information, in silico, for the human renin gene (REN). We searched for chromatin contacts and boundaries and the locations of super-enhancers that are involved in cell specific differentiation. The REN promoter was connected via RNA polymerase II binding to promoters of 12 neighboring genes on chromosome 1q32.1 over a distance of 762,497 bp. This constitutes a regulatory archipelago. The genes formed 3 topologically associated domains (TADs), as follows: TAD1: ZC3H11A, SNRPE, LINC00303; SOX13; TAD2: ETNK2, REN, KISS1, GOLT1A; TAD3: PLEKHA6, LINC00628, PPP1R15B, PIK3C2B, MDM4. REN in TAD2, was isolated from its neighboring genes in TAD1 and TAD3 by CTCF-binding sites that serve as insulators. TAD1 and TAD3 genes SOX13 and LINC00628 overlapped super-enhancers, known to reside near nodes regulating cell identity, and were co-expressed in various tissues, suggesting co-regulation. REN was also connected with 62 distant genes genome-wide, including the angiotensin II type 1 receptor gene. The findings lead us to invoke the following novel hypothesis. While the REN promoter is isolated from neighboring super-enhancers in most cells by insulators, these insulators break down with cell age to permit the inappropriate expression of REN in non-kidney cells by using the neighboring super-enhancers, resulting in expression in a wider spectrum of tissues, contributing to aging-related immune system dysregulation, cardiovascular diseases and cancers. Research is needed to confirm this hypothesis experimentally.

Curcumin induces multiple signaling pathways leading to vascular smooth muscle cell senescence Abstract Curcumin, a phytochemical present in the spice named turmeric, and one of the promising anti-aging factors, is itself able to induce cellular senescence. We have recently shown that cells building the vasculature senesced as a result of curcumin treatment. Curcumin-induced senescence was DNA damage-independent; however, activation of ATM was observed. Moreover, neither increased ROS production, nor even ATM were indispensable for senescence progression. In this paper we tried to elucidate the mechanism of curcumin-induced senescence. We analyzed the time-dependence of the level and activity of numerous proteins involved in senescence progression in vascular smooth muscle cells and how inhibition p38 or p38 together with ATM, two proteins involved in canonical signaling pathways, influenced cell senescence. We showed that curcumin was able to influence many signaling pathways of which probably none was dominant and sufficient to induce senescence by itself. However, we cannot exclude that the switch between initiation and progression of senescence is the result of the impact of curcumin on signaling pathways engaging AMPK, ATM, sirtuin 1 and p300 and on their reciprocal interplay. Cytostatic concentration of curcumin induced cellular stress, which exceeded the adaptive response and, in consequence, led to cellular senescence, which is triggered by time dependent activation of several signaling pathways playing diverse roles in different phases of senescence progression. We also showed that activity of β-glucuronidase, the enzyme involved in deconjugation of the main metabolites of curcumin, glucuronides, increased in senescent cells. It suggests a possible local elevation of curcumin concentration in the organism.

The protective function of non-coding DNA in DNA damage accumulation with age and its roles in age-related diseases Abstract Aging is a progressive decline of physiological function in tissue and organ accompanying both accumulation of DNA damage and reduction of non-coding DNA. Peripheral non-coding DNA/heterochromatin has been proposed to protect the genome and centrally-located protein-coding sequences in soma and male germ cells against radiation and the invasion of exogenous nucleic acids. Therefore, this review summarizes the reduction of non-coding DNA/heterochromatin (including telomeric DNA and rDNA) and DNA damage accumulation during normal physiological aging and in various aging-related diseases. Based on analysis of data, it is found that DNA damage accumulation is roughly negatively correlated with the reduction of non-coding DNA and therefore speculated that DNA damage accumulation is likely due to the reduction of non-coding DNA protection in genome defense during aging. Therefore, it is proposed here that means to increase the total amount of non-coding DNA and/or heterochromatin prior to the onset of these diseases could potentially better protect the genome and protein-coding DNA, reduce the incidence of aging-related diseases, and thus lead to better health during aging.

d -Galactose-induced accelerated aging model: an overview Abstract To facilitate the process of aging healthily and prevent age-related health problems, efforts to properly understand aging mechanisms and develop effective and affordable anti-aging interventions are deemed necessary. Systemic administration of d-galactose has been established to artificially induce senescence in vitro and in vivo as well as for anti-aging therapeutic interventions studies. The aim of this article is to comprehensively discuss the use of d-galactose to generate a model of accelerated aging and its possible underlying mechanisms involved in different tissues/organs.

Development, lifespan and reproduction of spider mites exposed to predator-induced stress across generations Abstract Predator-induced stress shows pronounced effects on prey by inducing behavioural, morphological, and physiological responses. Increasing evidence shows that these antipredator responses may also lead to changes in life-history traits such as aging and lifespan. However, little is known about how predator cues influence the fitness of preys and their transgenerational effects. Parental spider mites (Tetranychus urticae) were either raised on a leaf disc with or without cues from a natural predator (Phytoseiulus persimilis). The results showed that predator cues prolonged the development of both sexes, shortened female adult lifespan but not that of males, and reduced lifetime reproductive outputs of the females. The studies with offspring from both cues-exposed and control mothers demonstrated that parental effects were significant in the early developmental stage of offspring, but not in later life stages. The lifespan of offspring was strongly negatively affected by the predator-induced stress when they were directly exposed but not the stress-experienced by their mothers. Additionally, the parental effects in the earlier life stage were sex-specific, with delayed hatching in daughters (but not sons) when parents were exposed to predator-induced stress. This cross-transgenerational study indicated that there were deleterious effects of predator-induced stress on aging and lifespan of prey for both parents and their offspring, although the parental effects appeared to be weak (in the early stage of offspring but diminished in adult stage). This study highlighted the sex-difference of prey in response to predator-induced stress and sex-dependent parental effects on the offspring.

A 2D analysis of correlations between the parameters of the Gompertz–Makeham model (or law?) of relationships between aging, mortality, and longevity Abstract When mortality (μ), aging rate (γ) and age (t) are treated according to the Gompertz model μ(t) = μ0eγt (GM), any mean age corresponds to a manifold of paired reciprocally changing μ0 and γ. Therefore, any noisiness of data used to derive GM parameters makes them negatively correlated. Besides this artifactual factor of the Strehler–Mildvan correlation (SMC), other factors emerge when the age-independent mortality C modifies survival according to the Gompertz–Makeham model μ(t) = C+μ0eγt (GMM), or body resources are partitioned between survival and protection from aging [the compensation effect of mortality (CEM)]. Theoretical curves in (γ, logμ0) coordinates show how μ0 decreases when γ increases upon a constant mean age. Within a species-specific range of γ, such “isoage” curves look as nearly parallel straight lines. The slopes of lines constructed by applying GM to survival curves modeled according to GMM upon changes in C are greater than the isoage slopes. When CEM is modeled, the slopes are still greater. Based on these observations, CEM is shown to contribute to SMC associated with sex differences in lifespan, with the effects of several life-extending drugs, and with recent trends in survival/mortality patterns in high-life-expectancy countries; whereas changes in C underlie differences between even high-life-expectancy countries, not only between high- and low-life-expectancy countries. Such interpretations make sense only if GM is not merely a statistical model, but rather reflects biological realities. Therefore, GM is discussed as derivable by applying certain constraints to a natural law termed the generalized Gompertz–Makeham law.