As the nematode Caenorhabditis elegans ages, muscle expression of transcription factor UNC120/SRF declines. As this gene is also found in human muscle tissue, these findings could pave the way for treatments to improve the healthy aging process.
At first sight, the nematode Caenorhabditis elegans (C. elegans) has very little in common with humans… yet it has long been used in medical research. Many of its genes are, in fact, still found in higher mammals. Furthermore, some of its cellular and molecular mechanisms are also found in humans. A team of researchers also recently used this animal model to describe a mechanism related to muscle aging which could exist in humans: according to their findings, C. elegans muscle function is genetically influenced. Hence, with aging, C. elegans muscle expresses declining levels of transcription factor UNC-120, responsible for the expression of various genes involved in muscle contraction. This phenomenon is said to explain the lower mobility of aging nematodes. By maintaining expression of UNC-120/SRF, it would nonetheless be possible to delay muscle aging in the nematode.
In humans, UNC-120 is known as SRF. Furthermore, since expression of the latter has been shown to decrease with aging in elderly subjects, extrapolation of these results from the nematode to humans seems possible. This would allow new therapeutic perspectives to be confidently envisaged: "Developing life-extending treatments raises a number of ethical issues", explains Florence Solari* who led this research. However, having access to treatments which improve healthy aging, without modifying longevity, offers an interesting alternative".
From muscle aging to the aging body...
However, researchers nonetheless need to pass through many other stages before then. Firstly, additional genetic investigations: "Our findings show that other genes involved in the muscle aging phenomenon have yet to be identified. We therefore need to conduct new studies in C. elegans", states the researcher. Our work will now be easier, given the greater knowledge of muscle tissue physiology derived from the initial research: "A large part of this research involved describing the muscle tissue aging process in the nematode, which had been relatively unclear until now, through a series of preliminary investigations". By comparing the cell functions in nematodes, according to their longevity, the researchers were able to identify relevant biomarkers, such as mitochondrial fragmentation or the accumulation of autophagosomes. These criteria will be able to be used in the forthcoming investigations. Other perspectives also involve conducting similar research to study the changes in other tissues or organs over time.
Healthy aging is both an individual and collective goal. To achieve this, it is vital to understand the aging process for tissues and organs. This research proves that genome studies are essential in this field, to access these mechanisms: "Since the 1980s, numerous research conducted on model organisms have shown that longevity is influenced by genes", explains Florence Solari. We know that environment plays a predominant role in human longevity, notably owing to studies on true twins. However, our body's response to the environment largely depends on our genetic inheritance".
The promise of healthy aging therefore seems to be an accessible goal, even though it is still a long way off…
* Inserm Unit 1217/CNRS/Université Lyon 1, C. elegans Genetics and Neurobiology team, Institut NeuroMyoGene, Villeurbanne
Mergoud Dit Lamarche A et al. UNC-120/SRF independently controls muscle aging and lifespan in Caenorhabditis elegans. Aging Cell. 2018 Jan 3. doi: 10.1111/acel.12713.