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.

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.

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.

Individual barnyardgrass plants were grown in the absence of competition in a common garden environment. Cohorts were initiated in mid-March, late April, early June, mid-July, mid-August, and mid-September. Plants within a cohort varied from prostrate to upright. Early and late cohorts required slightly longer to achieve flowering and seed shatter than those initiated in late spring and early summer. The onset and development of senescence varied by as much as 5 wk between individuals within a cohort, and senescence progressed more rapidly for plants in later cohorts. Longest tiller length per plant averaged 150 cm and did not differ by cohort, but within cohort variation was approximately 33%. The number of tillers per plant declined with increasing delay in cohort initiation; within cohort variation exceeded 40%. Leaf numbers decreased from more than 10,000 per plant to less than 400 per plant with increasing delay in cohort initiation date. Individuals within a cohort had more than two-fold variation in leaf numbers. The number of inflorescences decreased from more than 4500 per plant to less than 100 with increasing delay in cohort initiation. Mean inflorescence length and frequency of different inflorescence lengths per plant varied between plants within a cohort. Vegetative biomass exceeded 3000 g for many plants in the early cohorts, and decreased to less than 25 g per plant for some individuals in the September cohort. More than two-fold variation in biomass occurred between plants within a cohort. Plasticity in morphology and phenology may contribute to the success of barnyardgrass as a weed.

The effects of haloxyfop on elongation, mitotic index, and morphology of sorghum and unicorn-plant primary roots were examined. Elongation of sorghum roots was completely inhibited by haloxyfop concentrations of 10–6 M or greater 24 h after treatment, whereas unicorn-plant root elongation was unaffected by the same concentrations 72 h after treatment. Mitotic indices of sorghum roots were reduced by both 10–6 and 10–8 M haloxyfop, with the higher concentration reducing the index to near zero by 24 h of exposure. The mitotic indices of unicorn-plant roots were unaffected by the same levels of the herbicide after both 24- and 48-h treatment. Histological analyses showed that after 24 h exposure to 10–6 M haloxyfop, large vacuoles were present in cells at the root apex that normally did not exhibit these organelles. After 48 h of exposure many cells in the apical region appeared to lack visible cytoplasm and/or nuclei, and by 72 h only cell walls remained visibly evident, and many cells had collapsed. These changes are similar to those that occur in tissues undergoing senescence. Treatment of sorghum roots with 10–8 M haloxyfop did not cause discernible changes after 72 h. Unicorn-plant roots treated with 10–6 M haloxyfop appeared unaffected after 72 h.

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.

Des mécanismes moléculaires liant le cancer à la sénescence cellulaire sont présentement explorés. Les télomères (l'extrémité des chromosomes) raccourcissent à chaque division cellulaire et il a été proposé que ce raccourcissement soit l'horloge moléculaire qui déclenche le processus de la sénescence cellulaire. La re-expression de la télomérase, une enzyme qui aide à maintenir la longueur des télomères et à prévenir leur raccourcissement, est un événement fréquemment observé dans les cellules tumorales. Cette re-expression est probablement essentielle à la formation et à la croissance soutenue de la majorité des cancers.

The flow of time can be conceptualized either as a cycle or an arrow. We offer a combined view: a helix. Chronological age (geophysical time reference) is not necessarily identical to biological age (internal time reference), and aging does not necessarily imply senescence. A new scheme of senescence, based on homeodynamics (nonlinear mechanics and nonequilibrium thermodynamics), is introduced as a plausible physical basis for understanding senescence. We propose that energy throughput, initially constructive of forms and functions, becomes destructive once most of the available degrees of freedom have been “frozen out” by the construction. Senescence becomes manifested at that point.

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).

Nuclear DNA of wheat embryos was probed with a synthetic oligonucleotide (C3TA3C3TA3) to assess changes in the length of telomeres during storage and germination. Chromosomal DNA of dry embryos, especially those derived from long-term-stored caryopses, was considerably depleted of telomeric repeats, but, shortly after the start of imbibition, the chromosomal DNA became rich in sequences hybridizing to the telomeric probe. Simultaneously, newly synthesized telomere-related sequences appeared in an extrachromosomal form that could be separated from bulk nuclear DNA by velocity and isopycnic centrifugations. It is concluded that, in addition to typical repair events, rapid synthesis of telomeric repeats occurs in wheat embryos at the onset of germination.

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.