Research Perspective Advance Articles
Nuclear lipid droplets: a novel regulator of nuclear homeostasis and ageing
Figure 1. Age-dependent nLDs accumulation affects nuclear homeostasis. Over time, lipid droplets (LDs) accumulate progressively in the cytoplasm and within the nuclear lamina, closely associated with age-related changes in the nuclear lamina protein LMN-1 (the nematode homolog of lamin A/C), which supports nuclear morphology. This nLD accumulation may disrupt Lamin-Associated Domains (LADs), chromatin regions anchored to the nuclear periphery, leading to chromatin remodelling, heterochromatin destabilization, and compromised nuclear integrity, which are well-established hallmarks of ageing. Longevity-promoting interventions activate the lipase ATGL-1, regulated by HLH-30/TFEB, linking lipid metabolism to pathways that promote cellular longevity. These changes in nLDs could impact key nuclear processes, including gene expression and DNA repair, thereby contributing to cellular ageing. Created in BioRender (Palikaras, K., 2024, https://BioRender.com/t49f941).