C. elegans feed yolk to their young in a form of primitive lactation

Kern, Carina; Townsend, StJohn; Salzmann, Antoine; Rendell, Nigel B.; Taylor, Graham W.; Comisel, Ruxandra M.; Foukas, Lazaros C.; Bähler, Jürg

doi:10.1038/s41467-021-25821-y

Cited by 30 publications

(45 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our research raises the possibility that these proteins may mediate or respond to signals from sperm. Also, both reproductive aging and C. elegans yolk secretion are regulated by insulin/insulin-like growth factor signaling (Luo et al 2010; Kern et al 2021). How reproductive aging and sperm depletion signals are integrated through this pathway to enact distinct phenotypes that impact germline function remains unknown but opens an avenue for future investigation.…”

Section: Discussionmentioning

confidence: 99%

Aging and sperm signals alter DNA break formation and repair in theC. elegansgermline

Toraason

Adler

Libuda

2022

Preprint

View full text Add to dashboard Cite

Female reproductive aging is associated with decreased oocyte quality and fertility. The nematode Caenorhabditis elegans is a powerful system for understanding the biology of aging and exhibits age-related reproductive defects that are analogous to those observed in many mammals, including dysregulation of DNA repair. C. elegans germline function is influenced simultaneously by both reproductive aging and signals triggered by limited supplies of sperm, which are depleted over chronological time. To delineate the causes of DNA repair defects in aged C. elegans germlines, we assessed both DNA double strand break (DSB) induction and repair during meiotic prophase progression in aged germlines which were depleted of self-sperm, mated, or never exposed to sperm. We find that germline DSB induction is dramatically reduced only in hermaphrodites which have exhausted their endogenous sperm, suggesting that a signal due specifically to sperm depletion downregulates DSB formation. We also find that DSB repair is delayed in aged germlines regardless of whether hermaphrodites had either a reduction in sperm supply or an inability to endogenously produce sperm. These results demonstrate that in contrast to DSB induction, DSB repair defects are a feature of C. elegans reproductive aging independent of sperm presence. Finally, we demonstrate that the ubiquitin E2 ligase variant UEV-2 is required for efficient DSB repair specifically in young germlines, implicating UEV-2 in the regulation of DNA repair during reproductive aging. In summary, our study demonstrates that DNA repair defects are a feature of C. elegans reproductive aging and uncovers parallel mechanisms regulating efficient DSB formation in the germline.Author SummaryAging leads to a decline in the quality of the female reproductive cells, known as oocytes. Oocytes subjected to reproductive aging experience an increase in both infertility and aneuploidies that cause miscarriages and birth defects. The nematode Caenorhabditis elegans is a classic model system used to determine the mechanisms of aging. Old C. elegans oocytes accrue many defects which may contribute to their reduced quality, including dysregulation of DNA repair. C. elegans fertility and germline function is also regulated oocyte-independently by sperm-dependent signals. To determine how aging and sperm may independently impact DNA repair in aging C. elegans oocytes, we control oocyte aging and sperm presence independently to evaluate their effects on DNA break formation and repair. We find that running out of sperm reduces the levels of DNA breaks which are produced, but the efficiency of DNA repair declines during aging independent of sperm effects. We also identify a protein which specifically promotes DNA repair in the oocytes of young animals, suggesting that this protein may regulate DNA repair in the germline during aging. Taken together, our research defines aging-specific and aging-independent mechanisms which regulate the genome integrity of oocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Aging and sperm signals alter DNA break formation and repair in theC. elegansgermline

Toraason

Adler

Libuda

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…(D) Intestinal atrophy as a cost of lactation. The recent demonstration that yolk is vented, and of promotion of larval growth by vented yolk, implies that later yolk production is not futile run-on, and that gut atrophy is a cost of lactation ( Kern et al, 2021 ).…”

Section: Identifying Proximate Mechanisms Of Aging: Stochastic or Pro...mentioning

confidence: 99%

“…However, our more recent findings imply that this was still not correct. We recently described how post-reproductive C. elegans vent yolk through the vulva, and that such yolk can be consumed by larvae, promoting their growth ( Kern et al, 2021 ). This implies that vented yolk serves a function similar to milk ( yolk milk ), though whether this behavior really promotes fitness in the wild remains to be demonstrated.…”

Section: Nematode Lactation: a Costly Programmentioning

confidence: 99%

“… Blocking reproductive death in semelparous species strongly increases lifespan, while gonadectomy in iteroparous species overall does not. Effects on lifespan of germline ablation in hermaphrodite but not female nematodes of several species resemble effects of blocking reproductive death in semelparous species ( Kern et al, 2021 ). Values for nematodes from a recent report ( Kern et al, 2021 ), and for other species from a recent review ( Gems et al, 2021 ); where there are multiple studies of the same species, only references with both male and female data are included, and for A. anguila (eel) data from the more recent source ( Tesch, 1977 ).…”

Section: Elegans Is Semelparous: Reproductive Death and Adap...mentioning

confidence: 99%

See 1 more Smart Citation

Semelparous Death as one Element of Iteroparous Aging Gone Large

Kern

2022

Front. Genet.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Likewise, in C. elegans , telomere length is a determinant of longevity and lifespan ( Lim et al, 2001 ; Joeng et al, 2004 ) ( Figure 1 ). Although the senescence-related secretory phenotype in C. elegans is still poorly understood, senescence-like atrophy is responsible for the age-dependent loss of gonad cells in the distal tip of the germline ( de la Guardia et al, 2016 ), as well as insulin/IGF-1 signaling-dependent self-destruction of intestinal biomass ( Ezcurra et al, 2018 ; Kern et al, 2021 ). This indicates that this model organism might experience age-related senescence, but stem cell exhaustion has not been directly linked to aging in C. elegans.…”

Section: Introductionmentioning

confidence: 99%

C. elegans as an Animal Model to Study the Intersection of DNA Repair, Aging and Neurodegeneration

Naranjo-Galindo¹,

Ai²,

Fang³

et al. 2022

Front. Aging

View full text Add to dashboard Cite

Since its introduction as a genetic model organism, Caenorhabditis elegans has yielded insights into the causes of aging. In addition, it has provided a molecular understanding of mechanisms of neurodegeneration, one of the devastating effects of aging. However, C. elegans has been less popular as an animal model to investigate DNA repair and genomic instability, which is a major hallmark of aging and also a cause of many rare neurological disorders. This article provides an overview of DNA repair pathways in C. elegans and the impact of DNA repair on aging hallmarks, such as mitochondrial dysfunction, telomere maintenance, and autophagy. In addition, we discuss how the combination of biological characteristics, new technical tools, and the potential of following precise phenotypic assays through a natural life-course make C. elegans an ideal model organism to study how DNA repair impact neurodegeneration in models of common age-related neurodegenerative diseases.

show abstract

C. elegans feed yolk to their young in a form of primitive lactation

Cited by 30 publications

References 50 publications

Aging and sperm signals alter DNA break formation and repair in theC. elegansgermline

Aging and sperm signals alter DNA break formation and repair in theC. elegansgermline

Semelparous Death as one Element of Iteroparous Aging Gone Large

C. elegans as an Animal Model to Study the Intersection of DNA Repair, Aging and Neurodegeneration

Contact Info

Product

Resources

About