Two forms of death in ageing Caenorhabditis elegans
2017
Ageing generates senescent pathologies, some of which cause death. Interventions that delay or prevent lethal pathologies will extend lifespan. Here we identify life-limiting pathologies in Caenorhabditis elegans with a necropsy analysis of worms that have died of old age. Our results imply the presence of multiple causes of death. Specifically, we identify two classes of corpse: early deaths with a swollen pharynx (which we call ‘P deaths’), and later deaths with an atrophied pharynx (termed ‘p deaths’). The effects of interventions on lifespan can be broken down into changes in the frequency and/or timing of either form of death. For example, glp-1 mutation only delays p death, while eat-2 mutation reduces P death. Combining pathology and mortality analysis allows mortality profiles to be deconvolved, providing biological meaning to complex survival and mortality profiles. Despite its wide use in ageing research, the contribution of specific age-associated pathologies toC. elegansmortality is not well understood. Here the authors identify two types of death in worms, with either a swollen or a shrunken pharynx, that are differentially affected by age and mutations that extend worm lifespan.
1
Citations in 🌏 GeoScience
[
{
"id": "1973236",
"title": "A fln-2 mutation affects lethal pathology and lifespan in C. elegans",
"abstract": "Differences in genetic background in model organisms can have complex effects on phenotypes of interest. We previously reported a difference in hermaphrodite lifespan between two wild-type lines widely used by C. elegans researchers (N2 hermaphrodite and male stocks). Here, using pathology-based approaches and genome sequencing, we identify the cause of this difference as a nonsense mutation in the filamin gene fln-2 in the male stock, which reduces early mortality caused by pharyngeal infection. We show how fln-2 variation explains previous discrepancies involving effects of sir-2.1 (sirtuin deacetylase) on ageing, and show that in a fln-2(+) background, sir-2.1 over-expression causes an FUDR (DNA synthesis inhibitor)-dependent reduction in pharyngeal infection and increase in lifespan. In addition we show how fln-2 variation confounds effects on lifespan of daf-2 (insulin/IGF-1 signalling), daf-12 (steroid hormone signalling), and eat-2 (putative dietary restriction). These findings underscore the importance of identifying and controlling genetic background variation. C. elegans is a commonly used model organism in the study of ageing, and differences in genetic background can result in varying strain longevity. Here the authors demonstrate that a background mutation in fln-2 affects life-limiting pharyngeal infection and that in the mutant background the beneficial effect of sir-2.1 over-expression is suppressed.",
"source_url": "https://www.nature.com/articles/s41467-019-13062-z",
"doc_type": 4,
"year": 2019,
"issue": 1,
"volume": 10,
"first_page": 1,
"last_page": 10,
"citation_count": 1,
"reference_count": 14,
"venue": {
"id": 2110000199,
"name": "NATURE COMMUNICATIONS",
"abbr": ""
},
"author": [
{
"id": 1000302028,
"name": "Yuan Zhao"
},
{
"id": 1000425948,
"name": "Hongyuan Wang"
},
{
"id": 1001894539,
"name": "Richard J. Poole"
},
{
"id": 1001250109,
"name": "David Gems"
}
],
"field": [
{
"id": 2014617445,
"name": "Middle constrictor"
},
{
"id": 2017680085,
"name": "Parasagitta elegans"
},
{
"id": 2029842136,
"name": "Superior constrictor"
},
{
"id": 2010394661,
"name": "Superior pharyngeal constrictor muscle"
},
{
"id": 2037700029,
"name": "Superior pharyngeal constrictor"
},
{
"id": 2020633606,
"name": "Stolidobranchia"
}
],
"cite": [
{
"name": "GB/T 7714",
"text": "Zhao Yuan, Wang Hongyuan, Poole Richard J., et al. A fln-2 mutation affects lethal pathology and lifespan in C. elegans[J]. NATURE COMMUNICATIONS, 2019, 10(1): 1-10."
},
{
"name": "MLA",
"text": "Zhao, Yuan, et al. \"A fln-2 mutation affects lethal pathology and lifespan in C. elegans\" NATURE COMMUNICATIONS., vol. 10, no. 1, 2019, pp. 1-10."
},
{
"name": "APA",
"text": "Zhao Yuan, Wang Hongyuan, Poole Richard J., & Gems David (2019). A fln-2 mutation affects lethal pathology and lifespan in C. elegans. NATURE COMMUNICATIONS, 10(1), 1-10."
},
{
"name": "BibTeX",
"text": "@inproceedings{Acemap1973236,\n title=\"A fln-2 mutation affects lethal pathology and lifespan in C. elegans\",\n author=\"Yuan {Zhao} and Hongyuan {Wang} and {Richard J. Poole} and David {Gems}\",\n journal=\"NATURE COMMUNICATIONS\",\n volume=\"10\",\n number=\"1\",\n pages=\"1--10\",\n url=\"https://www.acemap.info/paper/1973236\",\n year=\"2019\"\n}"
}
]
}
]
