Heavy isotopes to avert ageing?

Oxidative modifications of cellular components by free radicals are thought to be the cause of ageing and age-associated diseases. Extensive prior research has aimed to lessen such damage by counteracting the free-radical oxidizers with antioxidants, but there have been no attempts to protect the oxidizer-targeted biomolecules by making them more stable against oxidation. A recent paper describes an original and promising method based on the use of non-radioactive heavy isotopes, which might enable living cells to resist the free-radical oxidation and consequently allow us to live a healthier, longer life.     

Mechanisms of ageing: public or private?

Ageing--the decline in survival and fecundity with advancing age is caused by damage to macromolecules and tissues. Ageing is not a programmed process, in the sense that no genes are known to have evolved specifically to cause damage and ageing. Mechanisms of ageing might therefore not be expected to be as highly conserved between distantly related organisms as are mechanisms of development and metabolism. However, evidence is mounting that modulators of the rate of ageing are conserved over large evolutionary distances. As we discuss in this review, this conservation might stem from mechanisms that match reproductive rate to nutrient supply.     

How might replicative senescence contribute to human ageing?

Cell senescence is the limited ability of primary human cells to divide when cultured in vitro. This eventual cessation of division is accompanied by a specific set of changes in cell physiology, morphology, and gene expression. Such changes in phenotype have the potential to contribute to human ageing and age-related diseases. Until now, senescence has largely been studied as an in vitro phenomenon, but recent data have for the first time directly demonstrated the presence of senescent cells in aged human tissues. Although a direct causal link between the ageing of whole organisms and the senescence of cells in culture remains elusive, a large body of data is consistent with cell senescence contributing to a variety of pathological changes seen in the aged. This review considers the in vitro phenotype of cellular senescence and speculates on the various possible routes whereby the presence of senescent cells in old bodies may affect different tissue systems.     

Does salinity induce early ageing of pea root tissue?

Summary The effect of salinity on ageing of pea roots was studied. The distance from the apex at which differentiation of xylem elements occurred and the relative increase in the function of pentose phosphate pathways were taken as parameters for maturation or ageing.Pea seeds (Pisum stivum L.) of the varieties Alaska and Dan were used in these experiments. The seeds were germinated and grown in vermiculite moistened with Hoagland's solution or Hoagland's solution containing either 96 or 120 mM NaCl. In Alaska roots salinity induced differentiation in a lower section of the root than in controls, and the increase in the function of the pentose phosphate pathway paralleled the advance of maturation. Salinity apparently induces earlier ageing in Alaska roots. This is not the case in Dan roots which tolerate slightly higher salinity levels than Alaska.This paper is dedicated to Professor Michael Evenari for his 75th birthday, in admiration and friendshipThis research was supported by a grant from The Hebrew University's Central Research Fund     

Does capacity of DNA replication change during in vitro ageing?

We described elsewhere how a lack of change in the rate of DNA chain elongation occurred during in vitro ageing of human diploid fibroblasts. Here we further examined the rate of actual incorporation of tritiated thymidine, the center-to-center distance of replicons and the length of each phase of the cell cycle in order to extend our previous results to the other aspects of DNA replication. The results obtained showed that the rate of net DNA synthesis, the replicon size and the duration of S phase did not change during in vitro ageing. Our findings indicated that the reason why the greater part of the cell population at high population doubling levels becomes incapable of proliferating might not be the gradual decline in the ability of DNA replication. The regulation system(s) of DNA replication may alter during the period of culturing without any change in the capacities of the DNA replication machinery and, consequently, the non-cycling cells increase.     

Vertebrate ageing: an evolutionary process with a genetic basis?

Theories that explain the persistence of ageing in the face of natural selection implicitly assume that there is a genetic basis for ageing. This has now for the first time been shown to be the case in two free-living populations of mammals.     

Zinc–gene interaction related to inflammatory/immune response in ageing

The pivotal role played by zinc-gene interaction in affecting some relevant cytokines (IL-6 and TNF-alpha) and heat shock proteins (HSP70-2) in ageing, successful ageing (nonagenarians) and the most common age-related diseases, such as atherosclerosis and infections, is now recognized. The polymorphisms of genes codifying proteins related to the inflammation are predictive on one hand in longevity, on the other hand they are associated with atherosclerosis or severe infections. Since the health life-span has a strong genetic component, which in turn also affected by nutritional factors like zinc, the association of these polymorphisms with innate immune response, zinc ion bioavailability and Metallothioneins (MT) homeostasis is an useful tool to unravel the role played by zinc-gene interactions in longevity, especially due to the inability of MT in zinc release in ageing and chronic inflammation. In ageing, this last fact leads to depressed innate immune response for host defence. In contrast, in very old age the inflammation is lower with subsequent more zinc ion bioavailability, less MT gene expression and satisfactory innate immunity. Therefore, the zinc-gene (IL-6, TNF-alpha, Hsp70-2) interactions, via MT homeostasis, are crucial to achieve successful ageing.     

p53 and ageing: too much of a good thing?

A recent report by Tyner et al.(1) suggests that p53 is bad for longevity. Heterozygotic mice carrying a p53 mutation that apparently enhances the stability of the wild-type protein showed shorter lifespans and faster ageing while also developing fewer tumours. This fits with the idea that cellular ageing is the price paid for better protection against unlimited proliferation of cancer cells. But other work shows that there is a strong positive association between DNA repair-mediated protection against cancer and ageing. So what are we to make of the new data with regard to overall understanding of the mechanisms of ageing?     

Stem cell ageing: does it happen and can we intervene?

Adult stem cells have become the focus of intense research in recent years as a result of their role in the maintenance and repair of tissues. They exert this function through their extensive expansion (self-renewal) and multipotent differentiation capacity. Understanding whether adult stem cells retain this capacity throughout the lifespan of the individual, or undergo a process of ageing resulting in a decreased stem cell pool, is an important area of investigation. Progress in this area has been hampered by lack of suitable models and of appropriate markers and assays to identify stem cells. However, recent data suggest that an understanding of the mechanisms governing stem cell ageing can give insight into the mechanism of tissue ageing and, most importantly, advance our ability to use stem cells in cell and gene therapy strategies.     

The actin cytoskeleton: a key regulator of apoptosis and ageing?

Evidence from many organisms has shown that the accumulation of reactive oxygen species (ROS) has a detrimental effect on cell well-being. High levels of ROS have been linked to programmed cell death pathways and to ageing. Recent reports have implicated changes to the dynamics of the actin cytoskeleton in the release of ROS from mitochondria and subsequent cell death.     

Oxidative damage, ageing, and life-history evolution: where now?

The idea that resources are limited and animals can maximise fitness by trading costly activities off against one another forms the basis of life-history theory. Although investment in reproduction or growth negatively affects survival, the mechanisms underlying such trade-offs remain obscure. One plausible mechanism is oxidative damage to proteins, lipids, and nucleic acids caused by reactive oxygen species (ROS). Here, we critically evaluate the premise that ROS-induced oxidative damage shapes life history, focussing on birds and mammals, and highlight the importance of ecological studies examining free-living animals within this experimental framework. We conclude by emphasising the value of using multiple assays to determine oxidative protection and damage. We also highlight the importance of using standardised and appropriate protocols, and discuss future research directions.     

DNA damage, cellular senescence and organismal ageing: causal or correlative?

Cellular senescence has long been used as a cellular model for understanding mechanisms underlying the ageing process. Compelling evidence obtained in recent years demonstrate that DNA damage is a common mediator for both replicative senescence, which is triggered by telomere shortening, and premature cellular senescence induced by various stressors such as oncogenic stress and oxidative stress. Extensive observations suggest that DNA damage accumulates with age and that this may be due to an increase in production of reactive oxygen species (ROS) and a decline in DNA repair capacity with age. Mutation or disrupted expression of genes that increase DNA damage often result in premature ageing. In contrast, interventions that enhance resistance to oxidative stress and attenuate DNA damage contribute towards longevity. This evidence suggests that genomic instability plays a causative role in the ageing process. However, conflicting findings exist which indicate that ROS production and oxidative damage levels of macromolecules including DNA do not always correlate with lifespan in model animals. Here we review the recent advances in addressing the role of DNA damage in cellular senescence and organismal ageing.     

Reduced mitochondrial and ascorbate–glutathione activity after artificial ageing in soybean seed

The effect of artificial ageing on the relationship between mitochondrial activities and the antioxidant system was studied in soybean seeds (Glycine max L. cv. Zhongdou No. 27). Ageing seeds for 18 d and 41 d at 40 °C reduced germination from 99% to 52% and 0%, respectively. In comparison to the control, malondialdehyde content and leachate conductivity in aged seeds increased and were associated with membrane damage. Transmission electron microscopy and Percoll density gradient centrifugation showed that aged seeds mainly contained poorly developed mitochondria in which respiration and marker enzymes activities were significantly reduced. Heavy mitochondria isolated from the interface of the 21% and 40% Percoll were analyzed. Mitochondrial antioxidant enzymes activities including superoxide dismutase, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase, and dehydroascorbate reductase were significantly reduced in aged seeds. A decrease in total ascorbic acid (ASC) and glutathione (GSH) content as well as the reduced/oxidized ratio of ASC and GSH in mitochondria with prolonged ageing showed that artificial ageing reduced ASC–GSH cycle activity. These results suggested an elevated reactive oxygen species (ROS) level in the aged seeds, which was confirmed by measurements of superoxide radical and hydrogen peroxide levels. We conclude that mitochondrial dysfunction in artificially aged seeds is due to retarded mitochondrial and ASC-GSH cycle activity and elevated ROS accumulation.     

Physiotherapy students’ perceptions of ageing – Playing narratives as a pedagogical innovation

Introduction and objectivesThere is a considerable lack of structure in training health professionals in geriatrics. The narratives can promote a collaborative reflection on different topics and might be used as a pedagogic strategy for undergraduate health students. This study aimed to explore the adoption of new perspectives on ageing after the implementation of dynamic narratives in the first graduate year for physiotherapy students.Materials and methodsAn exploratory qualitative study was performed. Participants were included if they were: ≥18 years old, physiotherapy students and agreed to participate. Physiotherapy students (n = 44) were recruited from the School of Health Sciences, Polytechnic Institute of Leiria. Two gaming sessions were performed to help students, as narrators, express their visions and ways to deal with the geriatrics field. Students’ perspectives about ageing at baseline (T1) and after the narratives experience (T2) were collected by answering the following question: What is your perception regarding ageing? Two evaluators were involved in qualitative data analysis by performing: (i) an individual analysis of themes/subthemes and a discussion meeting to evaluate discrepancies and to reach a consensus.ResultsNegative perceptions about ageing were referred 39 times at T1 (most of them related to restriction; deterioration subthemes). There were no negative perceptions registered at T2. Positive perceptions increased at T2, from n = 39 to n = 52, and three new subthemes emerged (beginning of something, fighting ageism, challenge).ConclusionThis study demonstrated the potential of narrative-based experiences as a desirable pedagogic methodology (board games-oriented) for geriatric education in undergraduate health students.