Biology subjects

Kern, C. C.

Publications and source records attributed to Kern, C. C..

3 recordsLinked to original sources

bioRxiv2025

A hierarchy of causes of death in senescent C. elegans

In experimental gerontology, lifespan is often interpreted as a metric of the rate of the overall aging process. However, interventions that increase lifespan can result from suppression of one or more individual late-life pathologies. Here we show how, in the nematode Caenorhabditis elegans, such pathologies can compete in a hierarchical fashion to cause death, such that removal of one cause of death can unmask another. Under standard culture conditions, a major cause of death in elderly C. elegans is infection by their bacterial food source. We report that only when such infection is prevented is lifespan extended by suppression of a second senescent pathology, teratoma-like uterine tumors. Thus, as in mammals, lifespan in wild-type C. elegans can be limited by naturally-occurring neoplasia. By contrast, blocking bacterial infection attenuated the life-shortening effects of vitellogenesis, and did not unmask a life-shortening effect of distal gonad degeneration. Thus, depending on the masking or unmasking of competing causes of mortality in the hierarchy of causes of death, nematode lifespan limitation in different contexts can reflect action of distinct life-limiting senescent pathologies. This underscores how increases in lifespan do not necessarily reflect a reduction in overall aging rate.

pathology↗

bioRxiv2020

C. elegans hermaphrodites undergo semelparous reproductive death

Ageing in the nematode Caenorhabditis elegans is unusual in terms of the severity and early onset of senescent pathology, particularly affecting organs involved in reproduction (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002). In post-reproductive C. elegans hermaphrodites, intestinal biomass is converted into yolk leading to intestinal atrophy and yolk steatosis (Ezcurra et al., 2018; Sornda et al., 2019). We recently showed that post-reproductive mothers vent yolk which functions as a milk (yolk milk), supporting larval growth that is consumed by larvae (Kern et al., 2020). This form of massive reproductive effort involving biomass repurposing leading to organ degeneration is characteristic of semelparous organisms (i.e. that exhibit only a single reproductive episode) ranging from monocarpic plants to Pacific salmon where it leads to rapid death (reproductive death) (Finch, 1990; Gems et al., 2020). Removal of the germline greatly increases lifespan in both C. elegans and Pacific salmon, in the latter case by suppressing semelparous reproductive death (Hsin and Kenyon, 1999; Robertson, 1961). Here we present evidence that reproductive death occurs in C. elegans, and that it is suppressed by germline removal, leading to extension of lifespan. Comparing three Caenorhabditis sibling species pairs with hermaphrodites and females, we show that lactation and massive early pathology only occurs in the former. In each case, hermaphrodites are shorter lived and only in hermaphrodites does germline removal markedly increase lifespan. Semelparous reproductive death has previously been viewed as distinct from ageing; however, drawing on recent theories of ageing (Blagosklonny, 2006; de Magalhaes and Church, 2005; Maklakov and Chapman, 2019), we argue that it involves exaggerated versions of programmatic mechanisms that to a smaller extent contribute to ageing in non-semelparous species. Thus, despite the presence of reproductive death, mechanisms of ageing in C. elegans are informative about ageing in general.

genetics↗

bioRxiv2020

C. elegans provide milk for their young

Adult C. elegans hermaphrodites exhibit severe senescent pathology that begins to develop within days of reaching sexual maturity (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002; Wang et al., 2018). For example, after depletion of self-sperm, intestinal biomass is converted into yolk leading to intestinal atrophy and yolk steatosis (pseudocoelomic lipoprotein pools, PLPs) (Ezcurra et al., 2018; Garigan et al., 2002; Herndon et al., 2002; Sornda et al., 2019). These senescent pathologies are promoted by insulin/IGF-1 signalling (IIS), which also shortens lifespan (Ezcurra et al., 2018; Kenyon, 2010). This pattern of rapid and severe pathology in organs linked to reproduction is reminiscent of semelparous organisms where massive reproductive effort leads to rapid death (reproductive death) as in Pacific salmon (Finch, 1990; Gems et al., 2020). Moreover, destructive conversion of somatic biomass to support reproduction is a hallmark of reproductive death (Gems et al., 2020). Yet arguing against the occurrence of reproductive death in C. elegans is the apparent futility of post-reproductive yolk production. Here we show that this effort is not futile, since post-reproductive mothers vent yolk through their vulva, which is consumed by progeny and supports their growth; thus vented yolk functions as a milk, and C. elegans mothers exhibit a form of lactation. Moreover, IIS promotes lactation, thereby effecting a costly process of resource transfer from postreproductive mothers to offspring. These results support the view that C. elegans hermaphrodites exhibit reproductive death involving a self-destructive process of lactation that is promoted by IIS. They also provide new insight into how the strongly life-shortening effects of IIS in C. elegans evolved.

genetics↗