The occurrence of cardiovascular diseases increases with age independent of other risk factors, and the percentage of senescent cells is significantly elevated in vascular cells at atherosclerotic sites. Patients with accelerated aging syndromes caused by mutant lamin A protein, a structural component in nuclear lamina, also share many similarities with normal aged people, including the propensity to develop atherosclerosis. Recent studies have revealed the accumulation of prelamin A in normal aged vascular cells, and that lamin A participated as a mechanosensitive molecule in regulating various cellular events. These findings suggest that the ectopic expression of mutant lamin A or lamin A precursor (prelamin A) not only causes defects in cell mechanics, but it also disturbs stress-induced mechanotransduction pathways involving lamin A, both of which may contribute to vascular dysregulation. This review summarizes the current understanding of how lamin proteins are involved in vascular cell during aging, with a particular focus on the effect of mechanical stresses from blood flow on nuclear lamina of endothelial cells. Related studies are clarifying the role of lamin A in the progression of atherosclerosis, which will aid in the development of potential therapies for those suffering from lamin A-associated accelerated aging syndromes.

The protein kinase PINK1 and ubiquitin ligase Parkin promote removal of damaged mitochondria via a feed‐forward mechanism involving ubiquitin (Ub) phosphorylation (pUb), Parkin activation, and ubiquitylation of mitochondrial outer membrane proteins to support the recruitment of mitophagy receptors. The ubiquitin ligase substrate receptor FBXO7/PARK15 is mutated in an early‐onset parkinsonian–pyramidal syndrome. Previous studies have proposed a role for FBXO7 in promoting Parkin‐dependent mitophagy. Here, we systematically examine the involvement of FBXO7 in depolarization and mtUPR‐dependent mitophagy in the well‐established HeLa and induced‐neurons cell systems. We find that FBXO7−/− cells have no demonstrable defect in: (i) kinetics of pUb accumulation, (ii) pUb puncta on mitochondria by super‐resolution imaging, (iii) recruitment of Parkin and autophagy machinery to damaged mitochondria, (iv) mitophagic flux, and (v) mitochondrial clearance as quantified by global proteomics. Moreover, global proteomics of neurogenesis in the absence of FBXO7 reveals no obvious alterations in mitochondria or other organelles. These results argue against a general role for FBXO7 in Parkin‐dependent mitophagy and point to the need for additional studies to define how FBXO7 mutations promote parkinsonian–pyramidal syndrome.

Introduction-Vascular cells are regulated by continuous hemodynamic forces in vivo, and mechanical forces such as shear stress are proposed to involve in the progression of cardiovascular diseases such as atherosclerosis. Lamin A/C makes up the nuclear lamina, which structurally supports the nucleus while also functionally participates in chromatin organization and gene transcription. Diseases caused by lamin or other nuclear proteins are called laminopathies. One example, Hutchinson Gilford Progeria Syndrome (HGPS) where young patients show signs of accelerated aging, is caused by de novo mutations on the lamin A/C gene. Vasculature of HGPS patients shares many similarities with people of advanced age, suggesting a role for lamin in vascular aging. Methods-In this study, we examined how arterial shear stress affects lamin A/C expression in bovine aortic endothelial cells at different population doubling levels (PDL). We also used fluorescence image analysis to examine nuclear shape changes with shear stress and PDL. Results-Our results suggest that laminar shear stress downregulated lamin A/C expression in low PDL cells, but the effect was reversed in high PDL cells. Nuclear shape changes were more prominent after shear stress in low PDL cells. Moreover, lamin A/C accumulated more at the nuclear periphery after exposure to shear stress. Conclusions-Overall, our results indicate that both shear stress and cell passage can have an impact on lamin expressions at transcriptional and translational levels, as we continue to understand the effect of shear stress on endothelial lamina as part of the vascular aging process.