Research projects

Aging is the major and root factor leading to the onset of the chronic diseases of our century, including neurodegeneration, cancer, and heart-related diseases. Therefore, understanding the molecular basis of aging is critical to foster healthy aging.

At the cellular level, aging is caused by the accumulation of damage. This arises via deficiencies in protective mechanisms that maintain cellular homeostasis and increased exposure to damaging agents. Autophagy is a key cellular repair process that promotes longevity, whose efficiency, unfortunately, decreases during aging via unknown mechanisms. Conversely, genetic mobile elements such as LINE-1 retrotransposons can be a major source of harm, leading to DNA damage and deleterious inflammatory responses, processes that increase with age. The molecular changes that lead to autophagy dysregulation and uncontrolled activity of retrotransposons during aging are not well understood, and the potential correlation in their age-dependent variation is unknown. 

Recently, we described a regulatory pathway required for autophagy completion, which involves the phosphorylation of the core autophagy protein LC3B. LC3B phosphorylation regulates the binding of a set of proteins that may have autophagy-regulatory functions. Strikingly, these interactors have key functions in LINE-1 retrotransposon biology.  

We hypothesize that the autophagy machinery and LINE-1 retrotransposons are tightly connected through dual common interactors and influence each other in an unprecedented manner. We speculate that the autophagy/LINE-1 dual interactors are subject to agedependent changes that could explain autophagy and LINE-1 simultaneous dysregulation during aging. This proposal aims to decipher these intriguing questions and point out potential targets to promote healthy aging.