The aging process in semelparous and iteroparous species is different, but how different? Death in semelparous organisms (e.g., Pacific salmon) results from suicidal reproductive effort (reproductive ...death). Aging (senescence) in iteroparous organisms such as humans is often viewed as a quite different process. Recent findings suggest that the nematode
Caenorhabditis elegans
, widely used to study aging, undergoes reproductive death. In post-reproductive
C. elegans
hermaphrodites, intestinal biomass is repurposed to produce yolk which when vented serves as a milk to support larval growth. This apparent benefit of lactation comes at the cost of intestinal atrophy in the mother. Germline removal and inhibition of insulin/IGF-1 signaling (IIS) suppress
C. elegans
reproductive pathology and greatly increase lifespan. Blocking sexual maturity, e.g., by gonadectomy, suppresses reproductive death thereby strongly increasing lifespan in semelparous organisms, but typically has little effect on lifespan in iteroparous ones. Similarly, reduced IIS causes relatively modest increases in lifespan in iteroparous organisms. We argue that the more regulated and plastic mechanisms of senescence in semelparous organisms, involving costly resource reallocation under endocrine control, exist as one extreme of an etiological continuum with mechanisms operative in iteroparous organisms. We suggest that reproductive death evolved by exaggeration of mechanisms operative in iteroparous species, where other mechanisms also promote senescence. Thus, knowledge of
C. elegans
senescence can guide understanding of mechanisms contributing to human aging.
The nematode Caenorhabditis elegans exhibits rapid senescence that is promoted by the insulin/IGF-1 signalling (IIS) pathway via regulated processes that are poorly understood. IIS also promotes ...production of yolk for egg provisioning, which in post-reproductive animals continues in an apparently futile fashion, supported by destructive repurposing of intestinal biomass that contributes to senescence. Here we show that post-reproductive mothers vent yolk which can be consumed by larvae and promotes their growth. This implies that later yolk production is not futile; instead vented yolk functions similarly to milk. Moreover, yolk venting is promoted by IIS. These findings suggest that a self-destructive, lactation-like process effects resource transfer from postreproductive C. elegans mothers to offspring, in a fashion reminiscent of semelparous organisms that reproduce in a single, suicidal burst. That this process is promoted by IIS provides insights into how and why IIS shortens lifespan in C. elegans.
In post-reproductive C. elegans, destructive somatic biomass repurposing supports production of yolk which, it was recently shown, is vented and can serve as a foodstuff for larval progeny. This is ...reminiscent of the suicidal reproductive effort (reproductive death) typical of semelparous organisms such as Pacific salmon. To explore the possibility that C. elegans exhibits reproductive death, we have compared sibling species pairs of the genera Caenorhabditis and Pristionchus with hermaphrodites and females. We report that yolk venting and constitutive, early pathology involving major anatomical changes occur only in hermaphrodites, which are also shorter lived. Moreover, only in hermaphrodites does germline removal suppress senescent pathology and markedly increase lifespan. This is consistent with the hypothesis that C. elegans exhibit reproductive death that is suppressed by germline ablation. If correct, this would imply a major difference in the ageing process between C. elegans and most higher organisms, and potentially explain the exceptional plasticity in C. elegans ageing.
One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied ...that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype, or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence, it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition, and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts, such cells are normal and healthy and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent.” Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation—a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term
cellular senescence
with
remodeling activation
, and SASP with
RASP
(remodeling-associated secretory phenotype).
In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, ...which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in
C. elegans
and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in
C. elegans
, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those that involve costly resource reallocation, and exhibit endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in
C. elegans
can teach us about some mechanisms of senescence that are operative in iteroparous organisms.
During aging, etiologies of senescence cause multiple pathologies, leading to morbidity and death. To understand aging requires identification of these etiologies. For example, Caenorhabditis elegans ...hermaphrodites consume their own intestinal biomass to support yolk production, which in later life drives intestinal atrophy and ectopic yolk deposition. Yolk proteins (YPs; vitellogenins) exist as three abundant species: YP170, derived from vit-1-vit-5; and YP115 and YP88, derived from vit-6. Here, we show that inhibiting YP170 synthesis leads to a reciprocal increase in YP115/YP88 levels and vice versa, an effect involving posttranscriptional mechanisms. Inhibiting YP170 production alone, despite increasing YP115/YP88 synthesis, reduces intestinal atrophy as much as inhibition of all YP synthesis, which increases life span. By contrast, inhibiting YP115/YP88 production alone accelerates intestinal atrophy and reduces life span, an effect that is dependent on increased YP170 production. Thus, despite copious abundance of both YP170 and YP115/YP88, only YP170 production is coupled to intestinal atrophy and shortened life span. In addition, increasing levels of YP115/YP88 but not of YP170 increases resistance to oxidative stress; thus, longevity resulting from reduced vitellogenin synthesis is not attributable to oxidative stress resistance.
In this study the leaching of a one component (1K) structural epoxy model adhesive for the automotive industry is analysed via fourier transform infrared spectroscopy (FT-IR). In addition, the ...gravimetric water uptake and morphological changes were observed.
Findings indicate a two-stage water absorption at room temperature, whereas at 70 °C the water absorption shows a drastically increased value including a loss of mass after 500 h of immersion in DI-water. Water content at ambient conditions shows a dependency of the absolute humidity. FT-IR analyses of the dried eluate originating from immersion at 23 °C reveals typical bands of the latent hardener dicyandiamide and the filler CaCO3. On the other hand, the spectrum of the eluate originating from immersion at 70 °C exhibits bands of the fumed silica used as rheological additive. Microscopical observation by means of scanning electron microscopy (SEM) of the adhesive reveals that cavities arise in the vicinity of the inorganic particles contained in the adhesive due to water uptake.
•A novel, near to realism structural epoxy adhesive for scientific purposes.•Gravimetric water uptake in structural epoxy adhesive.•Leaching of substances.•Morphological changes upon water uptake.
Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune ...challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, than untrained monocytes.
, β-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca
uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes
in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm
. This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with
. Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.
Liposome-mediated delivery is a possible means to overcome several shortcomings with
C. elegans
as a model for identifying and testing drugs that retard aging. These include confounding interactions ...between drugs and the nematodes’ bacterial food source and failure of drugs to be taken up into nematode tissues. To explore this, we have tested liposome-mediated delivery of a range of fluorescent dyes and drugs in
C. elegans
. Liposome encapsulation led to enhanced effects on lifespan, requiring smaller quantities of compounds, and enhanced uptake of several dyes into the gut lumen. However, one dye (Texas red) did not cross into nematode tissues, showing that liposomes cannot ensure the uptake of all compounds. Of six compounds previously reported to extend lifespan (vitamin C,
N
-acetylcysteine, glutathione (GSH), trimethadione, thioflavin T (ThT), and rapamycin), this effect was reproduced for the latter four in a condition-dependent manner. For GSH and ThT, antibiotics abrogated life extension, implying a bacterially mediated effect. With GSH, this was attributable to reduced early death from pharyngeal infection and associated with alterations of mitochondrial morphology in a manner suggesting a possible innate immune training effect. By contrast, ThT itself exhibited antibiotic effects. For rapamycin, significant increases in lifespan were only seen when bacterial proliferation was prevented. These results document the utility and limitations of liposome-mediated drug delivery for
C. elegans
. They also illustrate how nematode-bacteria interactions can determine the effects of compounds on
C. elegans
lifespan in a variety of ways.
Heme catabolism exerts physiological functions that impact health through depressing inflammation. Upon reactive pathway progression, as in Gilbert's Syndrome (GS; UGT1A1*28 polymorphism), aggravated ...health effects have been determined. Based on lower inflammation and improved metabolic health reported for GS, inter-group differences in heme catabolism were explored. Therefore, a case-control study including 120 fasted, healthy, age- and gender matched subjects with/without GS, was conducted. Genetic expressions of HMOX-1 and BLVRA were measured. Additionally participants were genotyped for those polymorphisms that are known (UGT1A1*28) or likely (HMOX-1 microsatellites) to impact bilirubinemia. Intracellular interleukins (IL-6, IL-1β, TNFα), circulatory C-reactive protein (CRP), serum amyloid A (SAA) and haptoglobin (Hpt) were analysed as inflammatory markers. To assess intracellular heme oxygenase 1 (HO-1) isolated PBMCs were used. In GS vs. C, inflammation markers were significantly decreased. This was supported by an altered heme catabolism, indirectly reflecting in elevated unconjugated bilirubin (UCB; main phenotypic feature of GS) and iron, decreased hemopexin (Hpx) and Hpt and in up-regulated biliverdin reductase (BLVRA) gene expressions. Moreover, HMOX (GT)
short alleles were non-significantly more prominent in female GS individuals. Herewith, we propose a concept to elucidate why GS individuals encounter lower inflammation, and are thus less prone to oxidative-stress mediated diseases.
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