The Impact of Long Noncoding RNAs in Tissue Regeneration and Senescence

Abstract

Overcoming senescence with tissue engineering has a promising impact on multiple diseases. Here, we provide an overview of recent studies in which cellular senescence was inhibited through the up/downregulation of specific lncRNAs. This approach prevented senescence in the bones, joints, nervous system, heart, and blood vessels, with a potential impact on regeneration and the prevention of osteoarthritis and osteoporosis, as well as neurodegenerative and cardiovascular diseases. Senescence of the skin and liver could also be prevented through the regulation of cellular levels of specific lncRNAs, resulting in the rejuvenation of cells from these organs and their potential protection from disease. From these exciting achievements, which support tissue regeneration and are not restricted to stem cells, we propose lncRNA regulation through RNA or gene therapies as a prospective preventive and therapeutic approach against aging and multiple aging-related diseases.

Keywords: aging; cardiovascular disease; cellular senescence; downregulation; long noncoding RNAs; neurodegeneration; upregulation.

Figure 1

The impact of senescence-associated lncRNAs on the equilibrium between young and aged phenotypes. Aging is characterized by deleterious effects, including cell signaling dysfunctions, oxidative stress, inflammation, cell degeneration, and insulin resistance. Importantly, multiple lncRNAs can be regulated to revert these processes, resulting in enhanced cell viability and metabolism, as well as more specific effects, including improved cardiovascular function, protection against liver diseases, and increased cartilage and bone mass. In this figure, we included several examples of lncRNAs whose up- or downregulation could promote these effects though the inhibition of senescence.

Figure 2

Possible tissue engineering strategies for therapeutic up/downregulation of lncRNAs. Therapies could be based on nanoparticles coated with ligands recognizing a surface receptor overexpressed on target cells. (A) For upregulation, nanoparticles could be loaded with a lncRNA-expressing gene. (B) For downregulation, nanoparticles could be loaded with chemically modified lncRNA downregulatory oligonucleotides. LncRNA upregulation or downregulation are represented by upward or downward arrows, respectively.