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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.
Vitamin C (VC) is a vital micronutrient for humans and some other mammals and also has antioxidant activity. Stress-induced elevation of glucocorticoid production is well known to cause immunosuppression. The present study evaluated the effect of high VC intake on glucocorticoid-induced immune changes in mice. Senescence marker protein 30 knockout mice with genetic VC deficiency were fed a diet containing the recommended VC content (20 mg/kg per d; 0·02 %VC group) or a high VC content (200 mg/kg per d; 0·2 %VC group) for 2 months, then dexamethasone was given by intraperitoneal injection. After administration of dexamethasone, the plasma ascorbic acid concentration decreased significantly in the 0·02 %VC group and was unchanged in wild-type C57BL/6 mice on a VC-deficient diet (wild-type group), while it was significantly higher in the 0·2 %VC group compared with the other two groups. In the 0·02 %VC and wild-type groups, dexamethasone caused a significant decrease in the cluster of differentiation (CD)4+ and CD8+ T cells among splenocytes as well as a significant decrease in IL-2, IL-12p40 and interferon-γ protein production by splenocytes and a significant decrease in T-cell proliferation among splenocytes. In the 0·2 %VC group, these dexamethasone-induced immunosuppression improved when compared with the other two groups. In addition, reduction in the intracellular levels of ascorbic acid, superoxide dismutase and glutathione in splenocytes by dexamethasone as well as elevation in thiobarbituric acid-reactive substances were significantly suppressed in the 0·2 %VC group. These findings suggest that high dietary VC intake reduces glucocorticoid-induced T-cell dysfunction by maintaining intracellular antioxidant activity.
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.
Vitamin C (VC) is an essential nutrient for humans and certain other animals. It has antioxidant properties and has been reported to ameliorate oxidative damage to lipids, DNA and proteins. However, the effects of VC on immune function are poorly understood, especially the influence of long-term high-dose VC intake on the number and function of immune cells. In the present study, to evaluate the immune effects of VC, VC-deficient senescence marker protein-30 knockout (SMP30KO) mice were fed a diet containing the recommended level of VC (20 mg/kg per d; 0·02 % VC) or a high level of VC (200 mg/kg per d; 0·2 % VC) for 1 year. The plasma VC concentration of the 0·02 % group was the same as that of age-matched C57BL/6 mice after 1 year of feeding; however, plasma VC concentration and thymus weight were significantly higher in the 0·2 % VC group than in the 0·02 % VC group. The total counts of leucocytes, lymphocytes, granulocytes and monocytes in the peripheral blood, as well as the number of splenocytes and thymocytes, were all significantly higher in the 0·2 % VC group than in the 0·02 % VC group. In addition, the number of naive T cells in peripheral blood lymphocytes, the number of memory T-cell populations in splenocytes, and the number of cluster of differentiation (CD)4+CD8+ or CD4+CD8− or CD4−CD8+ T cells in thymocytes were all markedly higher in the 0·2 % VC group than in the 0·02 % VC group after 1 year of dietary treatment. These results suggest that a long-term high-dose intake of VC is effective in the maintenance of immune cells, partly through the suppression of age-related thymic involution in VC-deficient SMP30KO mice.
Cowpea is an important grain legume crop in sub-Saharan Africa (SSA) where, on a worldwide basis, the bulk is produced and consumed. The dry savanna area of SSA is where cowpea is mostly grown under rain-fed conditions. The crop is therefore prone to drought which may occur early, mid and/or late in the cropping season. Compared with many other crops, cowpea is drought tolerant, even though drought is still a major constraint limiting its productivity in SSA. Increasing the level of drought tolerance in existing cowpea varieties grown by farmers would enable them to obtain more and stable yield from their cowpea fields. As a first step towards enhancing drought tolerance in existing cowpea varieties, 1288 lines were selected randomly from cowpea germplasm collections maintained at the International Institute of Tropical Agriculture, and evaluated for their drought tolerance at Ibadan. Drought was imposed by withdrawal of irrigation from 5 weeks after sowing. On average, drought reduced the number of days to flower by 12 d, and the mean grain yield per plant was also reduced by 67.28%. A few of the cowpea lines stayed green for up to 6 weeks after irrigation was stopped, even though some of these produced no pods when the study was terminated. Further evaluation in the screenhouse of 142 selected drought-tolerant lines helped to identify six lines that could be potential parents for developing breeding lines with enhanced drought tolerance.
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.
Senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence, shows age-related deficits in learning and memory. We investigated the effect of oligomeric proanthocyanidins (oligomers) on memory impairment using the SAMP8 model involving the oral administration of oligomers for 5 weeks. To analyse memory improvement in SAMP8, we performed Morris water maze, object location and object recognition tests. The oral administration of oligomers improved spatial and object recognition impairment in SAMP8. Expressions of phosphorylated neurofilament-H (P-NF-H, axon marker), microtubule-associated proteins (MAP) 2a and 2b (MAP2; dendrite marker) and synaptophysin were increased in the brains of SAMP8-administered oligomers. In particular, the expression of P-NF-H was significantly elevated in the hippocampal CA1. This indicates that oligomers result in an increase in the densities of axons, dendrites and synapses. To investigate the protective mechanisms of oligomers against brain dysfunction with ageing, we carried out a receptor tyrosine kinase phosphorylation antibody array, and clarified that the administration of oligomers led to an increase in the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2, suggesting the neuroprotective role of oligomers. The phosphorylation of VEGFR-2 was more greatly increased in the hypothalamus and choroid plexus than in other brain regions of SAMP8. Memory in oligomer-treated mice was impaired by SU1498, a VEGFR-2-specific antagonist. Elucidating the relationship between memory impairment with ageing and VEGFR-2 signalling may provide new suggestions for protection against memory deficit in the ageing brain.
The senescence-accelerated mouse develops normally until 5–6 months of age and then displays rapid and irreversible advancement of senescence manifesting as clinical signs and gross lesions. To clarify the effect of lactic acid bacteria on the physiological changes with increasing age, heat-killed Lactococcus lactis G50 was administered to 1-month-old senescence-accelerated-prone mouse (SAMP)6 mice for 11 months, a senescence-accelerated mouse strain that develops senile osteoporosis. Mice fed G50 gained more weight than the control mice (not fed G50) during the feeding experiment. Faecal IgA levels in the mice fed G50 at 3 months were higher than those of the control mice but decreased to control levels with increasing age. The numbers of viable cells of Bacteroides sp., Lactobacillus sp., Staphylococcus sp., Enterococcus/Streptococcus sp. and Enterobacteriaceae sp. in faeces were similar for mice fed the G50 and control diets at any age, but strain G50 suppressed the intestinal growth of H2S-producing bacteria. Bone density of the thigh bone did not differ between aged G50 and control mice. Strain G50 would be a beneficial bacterium for the enhancement of intestinal immunity during youth and to suppress the growth of harmful intestinal bacteria. The applicability of strain G50 for the food and animal industries has been proposed in the present study.
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.
Neuroinflammation resulting from chronic reactive microgliosis is thought to contribute to age-related neurodegeneration, as well as age-related neurodegenerative diseases, specifically Alzheimer's disease (AD). Support of this theory comes from studies reporting a progressive, age-associated increase in microglia with an activated phenotype. Although the underlying cause(s) of this microglial reactivity is idiopathic, an accepted therapeutic strategy for the treatment of AD is inhibition of microglial activation using anti-inflammatory agents. Although the effectiveness of anti-inflammatory treatment for AD remains equivocal, microglial inhibition is being tested as a potential treatment for additional neurodegenerative disorders including amyotrophic lateral sclerosis and Parkinson's disease. Given the important and necessary functions of microglia in normal brain, careful evaluation of microglial function in the aged brain is a necessary first step in targeting more precise treatment strategies for aging-related neurodegenerative diseases. Studies from our laboratory have shown multiple age-related changes in microglial morphology and function that are suggestive of cellular senescence. In this manuscript, we review current knowledge of microglia in the aging brain and present new, unpublished work that further supports the theory that microglia experience an age-related decline in proliferative function as a result of cellular senescence.
The number of elderly people is increasing in less-developed countries. Although nutritional deficiencies and infectious diseases are generally more prevalent in resource-poor countries, the health and nutritional status of the elderly in South America in general, and in Ecuador, in particular, remains largely unstudied. The objective of the present study was to assess the nutritional, immunological and health status of elderly Ecuadorians. A cross-sectional study was conducted to evaluate a sample of elderly Ecuadorians with 24 h dietary recalls, biochemical and anthropometric measurements, delayed type hypersensitivity skin response and a health questionnaire. The 145 elders who enrolled had a mean age of 74·3 (sd 6·9) years. Of the subjects, 52 % exhibited BMI ≥25 kg/m2, whereas 9·1 % had BMI ≤20 kg/m2. Means of dietary intakes were below recommendations for most nutrients; exceptions were carbohydrate, fat, Fe and Se. Serum nutrient levels indicated that 50, 44, 43, 19 and 18 % of participants had deficiencies of Zn, Fe, vitamins B12 and D, and folate, respectively. The mean number of positive responses to seven recall antigens was 2·1 (sd 1·7) with an induration diameter of 9·9 (sd 7) mm, which are substantially lower than those reported for elders in developed countries. During the previous 6 months, 54 and 21 % of subjects reported at least one episode of respiratory infection or diarrhoea, respectively. Of these, 47 % sought care at a hospital or from a physician and 96 % from a relative or friend. In conclusion, while few elderly Ecuadorians were underweight, obesity was common. Micronutrient deficiencies were prevalent and may contribute to reduced immunological responses in this population.
Traditional explanations for the evolution of menopause and post-reproductive lifespan in human females have been based on the benefits of maternal or grand-maternal care outweighing the cost of lost reproduction. These explanations assume an evolutionary origin of menopause since human divergence with the most recent common ancestor. In this study, I conduct a literature survey of studies of 42 mammal species from eight orders, showing that post-reproductive lifespan appears to be widespread among mammals. I then propose an alternative to traditional hypotheses: following accepted theories of trade-offs and senescence, I suggest that the cost of extending reproductive lifespan might be relatively high in female mammals. Somatic and reproductive senescence appear to follow separate trajectories, so it is not surprising that the two processes should occur on different schedules. The timing of each process is probably determined by maximization of reproductive performance and survival early in adulthood, with consequent trajectories resulting in a post-reproductive lifespan. The early end of reproduction relative to lifespan may be due to the cost of production and/or maintenance of oocytes, which decline exponentially over time. Oocyte number below a threshold may trigger an end to normal hormonal cycling.
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.