Caenorhabditis Elegans

Aging is commonly defined as a nonreversible, ongoing, and (almost) unstoppable functional decline that is thought to eventually result in the death of the organism (Tosato et al. 2007). It seems to be an inevitable process in almost all known living organisms and is regulated by many different cellular pathways, and several factors (Uno and Nishida 2016). Remarkably, this process seems to be going on slower in some individuals and faster in others. Over the last decades, the rate of deaths among the older population has decreased (Shadyab and LaCroix 2015). People live longer in general and more people reach the age of 100 or higher (1:6000). Human longevity is still under investigation and the genetic basis of it is still unknown, but

The nematode Caenorhabditis elegans (C. elegans) is a widely used model organism. C. elegans is often used as a model organism to study aging and longevity, because of its small size (adult 1.5mm) and have a short lifespan (around 3 weeks) (Kaletsky and Murphy 2010). Conducting experiments with them is thus fast and less expensive than for example working with mice (lifespan >3 years). Due to C. elegans’ short lifespan and its genetic amiability, they are genetic modifications are easier to introduce and the worms are in general easier to handle in the laboratory. They have a transparent cuticle, which makes research especially on the extracellular matrix easier (Figure 1). Although C. elegans is smaller and has a shorter lifespan than humans, the nematode seems to be a suitable model organism to research human aging, as most of the genes in C. elegans are evolutionarily related to the genes present in the human DNA. Humans and C. elegans share a great amount of genetic information: 40% of genes are conserved and more than 70% of disease-associated genes are well conserved. What is unique about C. elegans is that their somatic cells do not divide, which leads to only a fixed number of cells. They have 959 somatic and about 2000 germ cells. This phenomenon is also called eutely. Also, they can be revived after long periods of freezing (>40 years at -80oC). Therefore,

A collagen that might play an important role in the ECM remodeling activity during aging is collagen 144 (col-144) (Ewald et al. 2015). Col-144 is an orthologs of the human surfactant protein D. Protein domain information indicates that col-144 is a structural constituent of cuticle (Shaye and Greenwald 2011). In C. elegans, researchers observed that col-144 is expressed as a factor in the ECM remodeling mechanism and that an overexpression of col-144 (and other types of collagens) is predicted to have an important role in slowing down the aging process (Budovskaya et al. 2008; Ewald et al. 2015).

Although the specific underlying aging processes are not completely clear, there are genes and pathways known which can enhance the lifespan. Gene mutations which are homologs or orthologs to the human insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) pathway can induce longevity and thus extend the lifespan of an organism (Bartke et al.