Elastin is an important component of the extracellular matrix in flexible tissues. It is, as the name might suggest, necessary for tissue elasticity. Elastin fibers in the extracellular matrix become damaged with age, and this process is thought to be important in a number of ways, not just because it alters the structural properties of the tissue, but also because it changes cell behavior for the worse. The presence of elastin fragments can provoke inflammation or other maladaptive responses, for example. It isn't entirely clear how best to tackle this aspect of aging, as elastin fibers are near all created during development, and cells make relatively little elastin in adult life. Some form of controlled recreation of developmental activities would likely be needed, coupled with some way to selectively clear out damaged elastin.
In today's open access paper, researchers review an entirely different aspect of elastin, meaning what it might be doing inside cells rather than outside cells in the extracellular matrix. Interestingly, elastin may be protective, acting to help cells resist cellular senescence in response to stress by interacting with mitochondria in some way. It remains unclear as to what is going on in detail; at this stage, researchers are taking the traditional path of disabling elastin expression and examining the consequences. Building a coherent picture of the underlying interactions that take place in a normal cell between elastin and mitochondria is a longer term prospect.
ELN regulates cellular senescence: emerging hypothesis for a non-canonical role
Tropoelastin, also named elastin, is an essential protein. It is encoded by the ELN gene as a secreted monomer. In the extracellular matrix, it undergoes complex and organized post-translation modifications, mainly crosslinking, to form mature elastic fibers. To date, research on ELN has been mainly focused on elastic fibers. Whether ELN also exerts non-canonical elastic fiber-independent functions, which could contribute to ELN role in physiological and pathological conditions, is barely known.
Elastic fibers are mainly produced during development and at young age, and then ELN expression decreases and largely ceases in adulthood. With aging, or during exposures that cause accelerating aging, elastic fibers are damaged without possibility of proper repair. This deterioration is thought to contribute to physiological tissue and organism aging as well as to pathological aging, altering parameters such as breath capacity during chronic obstructive pulmonary disease or blood circulation in some cardiovascular diseases.
In addition to exerting mechanical effects on tissues, the degradation of elastic fibers during the aging process or the development of age-related diseases also results in the production of elastin-derived peptides (EDP), also known as elastokines. These peptides have the potential to exert biological activity and have been linked to a range of detrimental effects, including those observed in pathologies associated with senescent cells.
The links of ELN or cellular senescence with the processes of aging and age-related diseases have prompted the suggestion that the two may be functionally connected. A key role of ELN in the regulation of cellular senescence has recently been demonstrated. Interestingly, this new function has been found to probably be independent of elastic fibers. All the studies concluded that ELN protects from cellular senescence, nevertheless the use of different tools and cells make more advanced direct comparison of the results hazardous.
Transcriptome and Gene Set Enrichment Analysis (GSEA) of fibroblasts upon ELN knockdown revealed a significant enrichment of a gene set associated with response to oxidative stress. An increase in mitochondrial reactive oxygen species was indeed detected early after ELN downregulation, supporting that ELN loss impacts mitochondria. We propose that loss of ELN results in alterations of the mitochondrial electron transport chain activity, which is a strong candidate to mediate reactive oxygen species production and senescence induction. Still, we can speculate that elastic fibers, by impacting elasticity and mechano-transduction, and/or when degraded by releasing elastokines and by inducing specific signaling, could also regulate cellular senescence through other mechanisms.
View the full article at FightAging
