Aging acts as a major risk factor for many human pathologies, including cancer, neurodegenerative disorders, diabetes, and cardiovascular diseases. Over the years, the global trend has been for people to live longer, with projections for 2030 indicating that individuals aged 60 and older will surpass the youth population and double the number of children under five. This has prompted a strong interest in aging research in the past decades. Nonetheless, additional information on the determinants of biological deterioration is still required if we aim at providing a better quality of life for aging individuals, together with creative and efficient ways to counteract them and prevent age-prone diseases.
In the LipLAge project, the focus was to understand why human cell nuclei tend to lose structural integrity as age progresses, ultimately leading to functional impairment. We envisioned a new paradigm where the lipid composition of the nuclear envelope, and not only proteins and nucleic acids, would have an active role in regulating the overall integrity of the nucleus. More specifically, our strategy was to address the interplay between lamin proteins and the lipids of the nuclear envelope, and to understand how these interactions affect nuclear lamina architecture and nuclear structure during human aging. Overall, our results show that, as age progresses, there is a significant decrease in the content of ether lipids in the nucleus of human skin cells. Moreover, this difference in membrane composition results in altered membrane biophysical properties, ultimately leading to a differential binding of lamin proteins to the nuclear envelope.
