TABLE 1.

Nuclear envelope proteins associated with or altered in the aging process

NE protein	Aging model	Alterations observed with aging	Cellular and molecular alterations	References
Lamin A/C	Physiological aging models: Human fibroblasts extensively passaged in culture Human centenarian fibroblasts Human aged‐iPSCs Human VSMCs from old donors Human aged‐iPSCs	Prelamin A accumulation at the nuclear periphery Depletion of nucleoplasmic lamin A/C Increase of lamin A expression in human aged‐iPSCs	Prelamin A/progerin accumulation cause the disruption of lamin A/C‐related functions, culminating in alterations in the nuclear structure and functions	Lattanzi et al. (2014), Petrini et al. (2017), Ragnauth et al. (2010), Scaffidi and Misteli (2006)
	Premature aging models: Human HGPS fibroblasts Human HGPS coronary arteries Zmpste24‐deficient mouse MEFs	Accumulation of progerin in the nuclear membrane in a cellular age‐dependent manner Depletion of nucleoplasmic lamin A/C induced by progerin expression		Candelario, Sudhakar, Navarro, Reddy, and Comai (2008), Goldman et al. (2004), Liu et al. (2005), McClintock et al. (2007), Olive et al. (2010), Rodriguez, Coppedè, Sagelius, and Eriksson (2009), Scaffidi and Misteli (2005), Vidak et al. (2015)
Lamin B1	Human diploid fibroblasts (WI‐38 cell line) extensively passaged in culture Human fibroblasts extensively passaged in culture Human fibroblasts from old donors Human progeria fibroblasts (mutation E145K) Human HGPS fibroblasts Senescent human fibroblasts Human aged‐iPSCs	Reduction of lamin B1 expression in human senescent and progeria fibroblasts, and in aged‐iPSCs Depletion of lamin B1 from the perinuclear region	Lamin B1 reduction is a consequence of senescence caused by activation of p53 and Rb Lamin B1 reduction in senescent cells is associated with unselective permeability of the NE Nuclear‐to‐cytoplasm chromatin blebbing (CCFs formation) in senescent cells is associated with the lamin B1 reduction Lamin B1 reduction seems to have a role in distension of satellite DNA, contributing to the appearance of SADs Lamin B1 protein turnover is achieved by autophagy in senescent cells Lamin B1 mRNA decreases early in senescence due to a decrease in its stability Lamin B1 silencing leads to the formation of misshapen nuclei and nuclear blebs	Dou et al. (2015), Dreesen, Chojnowski, et al. (2013), Dreesen, Ong, Ong, Chojnowski, and Colman (2013), Freund et al. (2012), Ivanov et al. (2013), Lattanzi et al. (2014), Liu et al. (2011), Petrini et al. (2017), Scaffidi and Misteli (2005), Shimi et al. (2011), Swanson et al. (2013), Taimen et al. (2009)
LAP2	Human HGPS fibroblasts Senescent human fibroblasts Human skin biopsies from old donors	Reduction in LAP2s (LAP2α and LAP2β) levels in HGPS, senescence and normal aging	Progerin expression down‐regulates LAP2α at the transcriptional level LAP2α decline contributes to the progerin‐dependent impaired proliferation in HGPS LAP2α deficiency changes lamin A/C–chromatin interactions toward heterochromatic regions	Dreesen, Chojnowski, et al. (2013), Gesson et al. (2016), Liu et al. (2011), Scaffidi and Misteli (2005), Vidak et al. (2015)
SUN1	Human HGPS fibroblasts Human centenarian fibroblasts LmnaΔE mutant mice	SUN1 is upregulated and accumulates at the NE and Golgi	SUN1 recruitment to the NE is enhanced due to higher affinity for both the progerin and farnesylated prelamin A, in HGPS and during normal aging, respectively Over accumulation of SUN1 arises from reduced protein turnover, rather than increased transcription SUN1 over accumulation at the NE correlates with NE abnormalities observed in HGPS, namely the heterochromatin profile and cellular senescence	Chen et al. (2012), Chen et al. (2014), Haque et al. (2010), Lattanzi et al. (2014)
Emerin	Human aged‐iPSCs Mouse HGPS fibroblasts	Increase of emerin expression Emerin is mislocated around nucleus	—	Petrini et al. (2017), Sola‐Carvajal et al. (2019)
Nesprin‐2	Human aged‐iPSCs Human HGPS fibroblasts	Increase of nesprin‐2 expression in human aged‐iPSCs Decrease of nesprin‐2 at the nuclear rim in human HGPS fibroblasts	—	Petrini et al. (2017); Sola‐Carvajal et al. (2019)
Nup153	Late passage VSMCs Human HGPS fibroblasts Caenorhabditis elegans	Nup153 mislocalization: decrease import into the nucleus and incorporation in NPCs Nup153 protein levels decrease	Nup153 mislocalization affects NPC assembly which impairs large cargo transportation to the nucleus and compromises the DNA damage repair	D’Angelo et al. (2009), Cobb et al. (2016), Larrieu et al. (2018)
Nup93	Old rat neurons nuclei Caenorhabditis elegans	Depletion of Nup93	Nup93 loss contributes to the age‐related deterioration of the NPC permeability barrier	D’Angelo et al. (2009)
Nup62	Old rat neurons nuclei	Depletion of Nup62	Nup62 loss contributes to the age‐related deterioration of the NPC permeability barrier	D’Angelo et al. (2009)
Tpr	HGPS fibroblasts	TPR mislocalization: decreased import into the nucleus and defective anchorage at NPCs	Disruption of the nuclear anchorage of the Tpr as a consequence of the failure to import Nup153 Tpr‐mediated anchorage of chromatin to the NE is compromised leading to chromatin disorganization and gene expression alterations	Larrieu et al. (2018), Snow, Dar, Dutta, Kehlenbach, and Paschal (2013)

CCFs, cytoplasmic chromatin fragments; HGPS, Hutchinson–Gilford progeria syndrome; INM, inner nuclear membrane; IPSCs, induced pluripotent stem cells; MEFs, mouse embryonic fibroblasts; NE, nuclear envelope; NPC, nuclear pore complex; SADs, senescence‐associated distension of satellites; VSMCs, vascular smooth muscle cells.