Kenyon C (2001) Cell "A conserved regulatory system for aging."

Kenyon C

[Cell, 2001]

While many processes in biology, such as cell differentiation and development, increase complexity, the aging process increases entropy and culminates in the death of the animal. Thus, the discovery that single gene mutations in many organisms can extend lifespan dramatically was surprising. These mutations indicated that the aging process is subject to regulation; it is not as random and haphazard as it seems. Even more surprising are some recent findings suggesting that a conserved system regulating lifespan may have arisen early in evolution.

Kenyon C (2005) Cell "The plasticity of aging: insights from long-lived mutants."

Kenyon C

[Cell, 2005]

Mutations in genes affecting endocrine signaling, stress responses, metabolism, and telomeres can all increase the life spans of model organisms. These mutations have revealed evolutionarily conserved pathways for aging, some of which appear to extend life span in response to sensory cues, caloric restriction, or stress. Many mutations affecting longevity pathways delay age-related disease, and the molecular analysis of these pathways is leading to a mechanistic understanding of how these two processesaging and disease susceptibility-are linked.

Kenyon C (2010) Ann N Y Acad Sci "A pathway that links reproductive status to lifespan in Caenorhabditis elegans."

Kenyon C

[Ann N Y Acad Sci, 2010]

In the nematode Caenorhabditis elegans and the fruit fly Drosophila, loss of the germline stem cells activates lifespan-extending FOXO-family transcription factors in somatic tissues and extends lifespan, suggesting the existence of an evolutionarily conserved pathway that links reproductive state and aging. Consistent with this idea, reproductive tissues have been shown to influence the lifespans of mice and humans as well. In C. elegans, loss of the germ cells activates a pathway that triggers nuclear localization of the FOXO transcription factor DAF-16 in endodermal tissue. DAF-16 then acts in the endoderm to activate downstream lifespan-extending genes. DAF-16 is also required for inhibition of insulin/insulin-like growth factor 1 (IGF-1) signaling to extend lifespan. However, the mechanisms by which inhibition of insulin/IGF-1 signaling and germline loss activate DAF-16/FOXO are distinct. As loss of the germ cells further doubles the already-long lifespan of insulin/IGF-1 pathway mutants, a better understanding of this reproductive longevity pathway could potentially suggest powerful ways to increase healthy lifespan in humans.

Kenyon C (2011) Philos Trans R Soc Lond B Biol Sci "The first long-lived mutants: discovery of the insulin/IGF-1 pathway for ageing."

Kenyon C

[Philos Trans R Soc Lond B Biol Sci, 2011]

Inhibiting insulin/IGF-1 signalling extends lifespan and delays age-related disease in species throughout the animal kingdom. This life-extension pathway, the first to be defined, was discovered through genetic studies in the small roundworm Caenorhabditis elegans. This discovery is described here.

Kenyon CJ (1985) Trends Genet "Heterochronic mutations of C. elegans--their developmental and evolutionary significance."

Kenyon CJ

[Trends Genet, 1985]

V. Ambros and R. Horvitz have identified a set of genes that may control the timing of developmental events in the nematode Caenorhabditis elegans. After hatching, C. elegans proceeds to the adult stage via four juvenile stages, each followed by a molt. Each juvenile stage is characterized by a distinct pattern of cell division and differentiation called an S1, S2, S3 or S4 lineage pattern. Ambros and Horvitz have found that the S1-S4 lineage patterns are modular; that is, a lineage pattern (including hypodermal, neuronal, muscle, and intestinal divisions and differentiations) characteristic of one stage can be expressed at a different stage. Each behaves as a complex lineage cassete that can be inserted into one or more of the available temporal slots.

Salser SJ et al. (1992) Trends Cell Biol "Activation of a C. elegans Antennapedia homologue in migrating cells controls their direction of movement. Nature 355, 255-258."

Kenyon C, Salser SJ

[Trends Cell Biol, 1992]

Mukhopadhyay A et al. (2006) Exp Gerontol "Worming pathways to and from DAF-16/FOXO."

Tissenbaum HA, Oh SW, Mukhopadhyay A

[Exp Gerontol, 2006]

In Caenorhabditis elegans, the insulin/IGF-1 signaling pathway controls many biological processes such as life span, fat storage, dauer diapause, reproduction and stress response . This pathway is comprised of many genes including the insulin/IGF-1 receptor (DAF-2) that signals through a conserved PI 3-kinase/AKT pathway and ultimately down-regulates DAF-16, a forkhead transcription factor (FOXO). DAF-16 also receives input from several other pathways that regulate life span such as the germline and the JNK pathway [Hsin, H., Kenyon, C., 1999. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362-366; Oh, S.W., Mukhopadhyay, A., Svrzikapa, N., Jiang, F., Davis, R.J., Tissenbaum, H.A., 2005. JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc. Natl. Acad. Sci. USA 102, 4494-4499]. Therefore, DAF-16 integrates signals from multiple pathways and regulates its downstream target genes to control diverse processes. Here, we discuss the signals to and from DAF-16, with a focus on life span regulation.

Tatar M (2002) Trends in Ecology & Evolution "Germ-line stem cells call the shots."

Tatar M

[Trends in Ecology & Evolution, 2002]

In the nematode Caenorhabditis elegans, developmental biologists find that tissues derived from embryonic germ-line progenitor cells regulate reproductive costs. New work from the laboratory of Cynthia Kenyon demonstrates that signals that reduce adult survival are mediated by a small set of progenitor descendants, the germ-line stem cells, and by their interaction with components of the endocrine system. Caenorhabditis elegans is now providing a new way of understanding the mechanisms of tradeoffs between reproduction and ageing.

Liu J et al. (2013) J Cell Biochem "Advance in research of microRNA in Caenorhabditis elegans."

Ai J, Liu J, Yang B

[J Cell Biochem, 2013]

microRNA (miRNA) is a family of small, non-coding RNA first discovered as an important regulator of development in Caenorhabditis elegans (C. elegans). Numerous miRNAs have been found in C. elegans, and some of them are well conserved in many organisms. Though, the biologic function of miRNAs in C. elegans was largely unknown, more and more studies support the idea that miRNA is an important molecular for C. elegans. In this review, we revisit the research progress of miRNAs in C. elegans related with development, aging, cancer, and neurodegenerative diseases and compared the function of miRNAs between C. elegans and human.

Coghlan A et al. (2006) Methods Mol Biol "Comparative genomics in C. elegans, C. briggsae, and other Caenorhabditis species."

Harris TW, Coghlan A, Stajich JE

[Methods Mol Biol, 2006]

The genome of the nematode Caenorhabditis elegans was the first animal genome sequenced. Subsequent sequencing of the Caenorhabditis briggsae genome enabled a comparison of the genomes of two nematode species. In this chapter, we describe the methods that we used to compare the C. elegans genome to that of C. briggsae. We discuss how these methods could be developed to compare the C. elegans and C. briggsae genomes to those of Caenorhabditis remanei, C. n. sp. represented by strains PB2801 and CB5161, among others (1), and Caenorhabditis japonica, which are currently being sequenced.