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A life-course approach to enhance tolerance to and prevent dementia and senescence is increasingly embraced by scientists, clinicians and policy makers to promote healthy ageing. Tolerance enhancement and prevention remain the most sensible courses of action given the lack of effective dementia treatment. We discuss the modifiable risk factors of dementia, and address social isolation and loneliness in view of their importance from a psychological and societal perspective. The effectiveness of prevention strategies and non-pharmacological intervention is increasingly supported by scientific evidence. They support an actionable model of dementia and senescence prevention that is cost effective and converges with established public health programmes (diet, exercise, mental health). They also relate to central societal issues (social inequality, pollution, healthcare), and translate to multidisciplinary professional interventions that are tailored to the individual. Changing lifestyle might be an effective way to address the challenges of dementia and senescence in our ageing populations, but also represents one of the most formidable psychosocial and societal challenges.
It is well accepted that the impact of diseases is generally more detrimental in elderly individuals than in younger ones. Changes in the immune system due to ageing can directly affect the ability to respond effectively to infections and may contribute to the higher morbidities and mortalities in the elderly population. Leishmaniasis is a complex of clinically unique diseases caused by obligate intracellular protozoa belonging to genus Leishmania, wherein visceral leishmaniasis (VL) is the most severe form and is fatal if left untreated. In this study, aged mice (72 weeks old) presented increased susceptibility to L. infantum infection compared to younger mice (4–6-week-old), with notable parasitism in both the spleen and liver, as well as exhibiting hepatosplenomegaly. A pronounced inflammatory profile was observed in the aged-infected mice, with excessive production of TNF-α and nitrite, along with diminished IFN-γ production and reduced proliferative capacity of T cells (assessed by expression of the Ki67 marker). Additionally, both CD4+ and CD8+ T cells from the aged-infected mice presented increased expression of the inhibitory receptors PD-1 and KLRG1 that strongly correlated with the parasitism found in the liver and spleen of this group. Overall, the data reported in this study suggests for the first time that ageing may negatively impact the VL outcome and provides a perspective for new therapeutic strategies involving manipulation of immunosenescence features against Leishmania infection.
Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that develops in or around the throat, larynx, nose, sinuses and mouth, and is mostly treated with a combination of chemo- and radiotherapy (RT). The main goal of RT is to kill enough of the cancer cell population, whilst preserving the surrounding normal and healthy tissue. The mechanisms by which conventional photon RT achieves this have been extensively studied over several decades, but little is known about the cell death pathways that are activated in response to RT of increasing linear energy transfer (LET), including proton beam therapy and heavy ions. Here, we provide an up-to-date review on the observed radiobiological effects of low- versus high-LET RT in HNSCC cell models, particularly in the context of specific cell death mechanisms, including apoptosis, necrosis, autophagy, senescence and mitotic death. We also detail some of the current therapeutic strategies targeting cell death pathways that have been investigated to enhance the radiosensitivity of HNSCC cells in response to RT, including those that may present with clinical opportunities for eventual patient benefit.
Two properties – robustness and plasticity – characterize development as the bridge between genotype and phenotype. Developmental robustness is the capacity of a developmental system to produce the same phenotype irrespective of changes in external conditions (and, to some extent, of genetic change). Developmental plasticity is the production of different phenotypes by individuals with the same genotype, as a response to exposure to different external conditions. This outcome is called polyphenism if there is a clear discontinuity between the produced phenotypes, e.g. male vs. female in the alligator, in response to different temperatures in a critical phase of embryonic development. Phenotypic differences are not restricted to morphology, but extend to the temporal dimension, e.g. in the annual, biennial or perennial habit of plants, or in their flowering calendar. Periodization of development is to some extent arbitrary even in organisms where the individual’s life is punctuated by events such as moults in arthropods. The determination of age is also to some extent arbitrary. Senescence is conspicuous (often dramatic) in many organisms, but apparently non-existent in others.
Apicomplexan parasites are well-known to modulate their host cells at diverse functional levels. As such, apicomplexan-induced alteration of host cellular cell cycle was described and appeared dependent on both, parasite species and host cell type. As a striking evidence of species-specific reactions, we here show that Eimeria bovis drives primary bovine umbilical vein endothelial cells (BUVECs) into a senescence-like phenotype during merogony I. In line with senescence characteristics, E. bovis induces a phenotypic change in host cell nuclei being characterized by nucleolar fusion and heterochromatin-enriched peripheries. By fibrillarin staining we confirm nucleoli sizes to be increased and their number per nucleus to be reduced in E. bovis-infected BUVECs. Additionally, nuclei of E. bovis-infected BUVECs showed enhanced signals for HH3K9me2 as heterochromatin marker thereby indicating an infection-induced change in heterochromatin transition. Furthermore, E. bovis-infected BUVECs show an enhanced β-galactosidase activity, which is a well-known marker of senescence. Referring to cell cycle progression, protein abundance profiles in E. bovis-infected endothelial cells revealed an up-regulation of cyclin E1 thereby indicating a cell cycle arrest at G1/S transition, signifying a senescence key feature. Similarly, abundance of G2 phase-specific cyclin B1 was found to be downregulated at the late phase of macromeront formation. Overall, these data indicate that the slow proliferative intracellular parasite E. bovis drives its host endothelial cells in a senescence-like status. So far, it remains to be elucidated whether this phenomenon indeed reflects an intentionally induced mechanism to profit from host cell-derived energy and metabolites present in a non-dividing cellular status.
Since the mid-1980s, swarms of the rhizostome Rhopilema nomadica have been an annual phenomenon in Israeli Mediterranean coastal waters during the summer months. Despite its annual prominence and the potential impact on food webs and ecosystem services, studies concerning its feeding ecology and its interactions with other biota in the marine food web have not been conducted. During summer 2015 gut contents of 41 R. nomadica were analysed as well as ambient plankton assemblages. More than 60% of the medusae diet was found to consist of microzooplankton <150 μm. Size correlations revealed that larger R. nomadica consumed faster swimming prey while smaller medusae relied more on the slower swimming taxa. The medusan diet reflected most of the ambient plankton taxa, but no statistically significant correlations between the relative abundance in diet and ambient plankton were found. As summer progressed, there was a gradual decrease in both mean medusa bell diameter (from 42.2–16 cm) and integrity of feeding structures. These findings suggest that R. nomadica, at least at the time of its appearance in Israeli coastal waters, may exert less predatory pressure on the plankton than we might otherwise expect.
The chapter “Aging Theory” makes three related points about the intersection of narrative, time, and aging. First, it draws on the idea of surface reading to argue for renewed attention to the effects of aging. By drawing aging to the surface of the body and its representation in the novel, this approach resists the modern tendency of repressing the duration of aging. The second section draws together the diachronic analyses of narrative theory with the metaphysics of Henri Bergson and Gilles Deleuze, contending that the reader’s temporal encounter with the materiality of a text’s discourse serves as a tacit reminder of the reader’s own aging. By doing so, narrative temporality reflects to the reader the very duration that falls out of his or her experience of aging. The final section suggests that the novel’s realism naturalizes a crisis model of character development by positing life-changing events as a part of “everyday” reality. As realism relies upon a model of change where duration surprisingly disappears, it diminishes the role of aging in the development of subjectivity over time.
Our brains are continuously changing and these changes alter brain functions. With maturation, there is growth and unfortunately, even with healthy aging, decline. Aging-related decrements affect neurons and their connectivity, neurotransmitter systems, and even support systems such as glia. Aging affects some brain regions (frontal lobes and hippocampi) more than others. This book reviews and discusses aging-related changes and their influence on the major neurobehavioral domains, beginning with reviews of aging-related changes in anatomy and physiology. Subsequent chapters review cross-sectional and longitudinal studies of aging-related changes in sensory perception (vision, hearing, touch, smell, taste) and cognitive functions (memory, language, motor planning, attention, executive functions, emotions, creativity). In each chapter, mechanisms that may account for these changes are discussed. Declines related to aging per se are distinguished from declines related to aging-associated diseases. Final chapters discuss what can potentially be done to slow or reverse aging-related decline of cognitive functions, including exercise, cognitive rehabilitation, and pharmacological agents. It is hoped this book will help clinicians differentiate between normal aging processes and brain diseases, reduce the adverse effects of brain aging, and stimulate further research on how adverse effects of brain aging can be reversed, stopped, modified, or best managed.
Chapter 1 introduces some fundamental concepts, starting with a tentative definition of reproduction that will be revised and enriched in the following chapters and with the traditional distinction between sexual and asexual reproduction. We address the delicate issues relating to the notions of biological individual, generation and life cycle (but we refrain from discussing these topics from a philosophical perspective). We also deal with the not always clearly defined relationship between reproductive and developmental processes, in particular those related to regeneration.
In the USA, western Washington (WWA) and the Alaska (AK) Interior are two regions where maritime and continental climates, high latitude and cropping systems necessitate early maturing spring wheat (Triticum aestivum L.). Both regions aim to increase the production of hard spring bread wheat for human consumption to support regional agriculture and food systems. The Nordic region of Europe has a history of breeding for early maturing spring wheat and also experiences long daylengths with mixed maritime and continental climates. Nordic wheat also carries wildtype (wt) NAM-B1, an allele associated with accelerated senescence and increased grain protein and micronutrient content, at a higher frequency than global germplasm. Time to senescence, yield, protein and mineral content were evaluated on 42 accessions of Nordic hard red spring wheat containing wt NAM-B1 over 2 years on experimental stations in WWA and the AK Interior. Significant variation was found by location and accession for time to senescence, suggesting potential parental lines for breeding programmes targeting early maturity. Additionally, multiple regression analysis showed that decreased time to senescence correlated negatively with grain yield and positively with grain protein, iron and zinc content. Breeding for early maturity in these regions will need to account for this potential trade-off in yield. Nordic wt NAM-B1 accessions with early senescence yet with yields similar to regional checks are reported. Collaboration among alternative wheat regions can aid in germplasm exchange and varietal development as shown here for the early maturing trait.
To quantitatively test the hypothesis that older patients have increased thyroarytenoid muscle atrophy by comparing thyroarytenoid muscle volumes across different age groups.
A retrospective chart review was conducted. The study included 111 patients with no history of laryngeal pathology. Two investigators reviewed magnetic resonance imaging studies of these patients and manually traced the thyroarytenoid muscles on multiple slices bilaterally. Thyroarytenoid muscle volumes were then computed using imaging analysis software. Patients were stratified into three age groups (18–50 years, 51–64 years, and 65 years or older) for comparison.
Intra- and inter-rater reliabilities were excellent for all measurements (intraclass correlation co-efficient > 0.90). There was no statistically significant difference in the mean volumes of left and right thyroarytenoid muscles in all age and gender groups.
Given the lack of statistically significant difference in thyroarytenoid muscle volume between age groups on magnetic resonance imaging, the prevailing assumption that age-related thyroarytenoid muscle atrophy contributes to presbyphonia should be re-examined.
The risk of developing cardiovascular diseases is known to begin before birth and the impact of the intrauterine environment on subsequent adult health is currently being investigated from many quarters. Following our studies demonstrating the impact of hypoxia in utero and consequent intrauterine growth restriction (IUGR) on the rat cardiovascular system, we hypothesized that changes extend throughout the vasculature and alter function of the renal artery. In addition, we hypothesized that hypoxia induces renal senescence as a potential mediator of altered vascular function. We demonstrated that IUGR females had decreased responses to the adrenergic agonist phenylephrine (PE; pEC50 6.50 ± 0.05 control v. 6.17 ± 0.09 IUGR, P < 0.05) and the endothelium-dependent vasodilator methylcholine (MCh; Emax 89.8 ± 7.0% control v. 41.0 ± 6.5% IUGR, P < 0.001). In IUGR females, this was characterised by increased basal nitric oxide (NO) modulation of vasoconstriction (PE pEC50 6.17 ± 0.09 IUGR v. 6.42 ± 0.08 in the presence of the NO synthase inhibitor N-nitro-l-arginine methyl ester hydrochloride (l-NAME; P < 0.01) but decreased activated NO modulation (no change in MCh responses in the presence of l-NAME), respectively. In contrast, IUGR males had no changes in PE or MCh responses but demonstrated increased basal NO (PE pEC50 6.29 ± 0.06 IUGR v. 6.42 ± 0.12 plus l-NAME, P < 0.01) and activated NO (Emax 37.8 ± 9.4% control v. −0.8 ± 13.0% plus l-NAME, P < 0.05) modulation. No significant changes were found in gross kidney morphology, proteinuria or markers of cellular senescence in either sex. In summary, renal vascular function was altered by hypoxia in utero in a sex-dependent manner but was unlikely to be mediated by premature renal senescence.
Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100–380 nm) and visible (380–760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (sd 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (sd 500) lx light (420–800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.
Predictions of survivorship are critical to quantify the probability of establishment by an alien invasive species, but survival curves rarely distinguish between the effects of temperature on development versus senescence. We report chronological and physiological age-based survival curves for a potentially invasive noctuid, recently described as Copitarsia corruda Pogue & Simmons, collected from Peru and reared on asparagus at six constant temperatures between 9.7 and 34.5°C. Copitarsia spp. are not known to occur in the United States but are routinely intercepted at ports of entry. Chronological age survival curves differ significantly among temperatures. Survivorship at early age after hatch is greatest at lower temperatures and declines as temperature increases. Mean longevity was 220 (±13 SEM) days at 9.7°C. Physiological age survival curves constructed with developmental base temperature (7.2°C) did not correspond to those constructed with a senescence base temperature (5.9°C). A single degree day survival curve with an appropriate temperature threshold based on senescence adequately describes survivorship under non-stress temperature conditions (5.9–24.9°C).
Several professional groups present themselves as ‘waging war’ on old age. They construct old age as a naturalised, self-evidently negative, biological phenomenon, which must be attacked and defeated. These groups make different claims to technical expertise and their ability to control natural phenomena, and use different weapons to defeat ageing. There are those who focus on cosmetic interventions, that is, the control of the body and the removal or masking of the signs of ageing. There are those who equate old age with ill-health and identify themselves as warriors in a battle with disease, and others whose objective is to understand the fundamental intra-cellular processes of ageing and what controls the human life span, and then to extend its limits. A fourth group aims to make human immortality possible. Examination of the language and symbolic practices of these groups reveals that they share a dominant cultural view that devalues old age and older people. The use of military metaphors to describe the importance and difficulties of their task is most prolific among the first and fourth of these groups. The second and third groups disguise a contradiction in their aim of understanding the diseases and disorders of old age by advocating the goal of an extended ‘healthy life span’, which avoids having to confront the moral dilemmas of extending the lifespan for its own sake.
The epiphytic habitat is assumed to be nutrient deficient, although this generally held notion is based almost completely on circumstantial evidence (Zotz & Hietz 2001). Most studies on the nutrient relations of vascular epiphytes focus on nitrogen (Bergstrom & Tweedie 1998, Hietz & Wanek 2003, Stewart et al. 1995). Although nitrogen plays a key role in limiting plant growth worldwide, there is an on-going discussion whether nitrogen or rather phosphorus are more limiting in many tropical forests (Grubb 1989, Harrington et al. 2001, Vitousek & Howarth 1991). To identify which nutritional factor is most limiting for plant growth, nutrient ratios have been proposed as a very useful tool (Koerselman & Meuleman 1996). These authors stated that N:P ratios exceeding 16 are indicative of P limitation, while an N:P ratio <14 suggests N limitation. Some reports of such ratios in the epiphyte literature indicate that phosphorus may indeed be limiting for epiphytes in tropical forests. For example, the N:P ratio of two field-grown bromeliads (Tillandsia circinnata and T. usneoides) decreased dramatically from 23.6 and 40.4, respectively, to 3.6 and 3.4, respectively, when fertilized with both N and P in the laboratory (Benzing & Renfrow 1974a). On the other hand, however, the average N:P ratios of mature leaves of 41 epiphyte species compiled from a number of papers did not appear particularly high (12.1±10.5, cf. Zotz & Hietz 2001).
Senescence can be defined as accelerating phenotypic deterioration with old age. For traits that grow throughout life, such as the horns of some ungulates, senescence may be expressed as a decrease in annual growth rates, or an increase in asymmetry, in the years preceding death. Age-specific yearly horn-growth segments of 378 male Alpine ibex Capra ibex L. that died from natural causes were analysed in the Gran Paradiso National Park (Italian Alps). Horn annuli displayed fluctuating asymmetry. The hypothesis that asymmetry and size of the annuli of the horns could predict annual survival probability was tested. It was found that between 5 and 11 years of age, male ibex that grew shorter annuli than the average for the population had a greater probability of mortality over the following years than those with greater rates of horn growth. Horn asymmetry and mortality rates were not significantly correlated. Annulus size, reflecting the onset of senescence, seemed to be a better indicator of individual quality than annulus asymmetry.
The FT-Raman spectra are described of green and red snow algae, Chlamydomona, involved in the colonization of exposed surfaces of the McLeod Glacier, Jane Col, Signy Island, situated at the northern edge of the Weddell Sea, Antarctica. The protective biochemicals produced by these extremophilic algae give rise to the so-called watermelon snow of Alpine regions. The red colour of the senescent algae is shown to derive from the accumulation of carotenoids and a deficiency of chlorophyll believed to arise from UV-radiation induced breakdown into phaecophytin. A comparison of the Raman spectra of young (green) and old (red) algae is effected and possible bio-markers for spectral detection on extraterrestrial icy moons and planets are identified.
The premise that there are genes that wield a strong influence on longevity has, until recently, not been a popular one and there has been no concerted effort to find such genes. However, the finding that single genes can have large effects on the lifespans of yeast, worms and flies raises the possibility that individual genes in mammals may similarly have relatively large effects on longevity. Recent advances in mammalian genetics, many associated with the large-scale efforts to sequence the human and mouse genomes, have accelerated the search for longevity genes, principally in mice. Here, we review results using animal models that have recently shed light on genes regulating longevity and ageing patterns. A large number of genetically defined strains of mice are available and this, together with their established history of use in genetic research and their relatively short lifespans, has made murine models particularly useful. We also review our own work in which genes regulating mouse lifespan and those regulating cell cycling of haematopoietic progenitor cells have been mapped to the same locations in the genome. These results suggest that some of the same genes affect both traits, and further suggest a cause-and-effect relationship between cumulative cell-cycle activity and longevity of an organism.
Procellariform seabirds provide a good model for studies of the causes and consequences of variability in avian egg size, because females can only adjust reproductive investment by breeding intermittently, or by altering the size of their single egg. Maternal characteristics such as age, breeding experience and body size, as well as environmental variability, can influence egg size, but the effect of these factors has rarely been assessed simultaneously in the same study. Previous studies in Scotland have shown that the egg size of northern fulmars Fulmarus glacialis increased in relation to breeding experience. At this colony the influence of breeding experience, body size and inter-annual variability upon egg size was tested simultaneously. Data collected over seven breeding seasons between 1975 and 2002 showed that egg size varied significantly both between years and in relation to the length of the breeding experience of females, but that female body size explained most variation in egg size. Inter-annual variability in egg size was not related to the winter North Atlantic Oscillation, which had recently been shown to influence other measures of reproductive success at this colony. Larger eggs also seem to be more likely to produce successful fledglings. These findings are discussed in relation to the relative contribution of egg quality and parental quality on increased reproductive success.