the nuclear envelope ( ne ) is a biostructure , which separates the nuclear and cytoplasmic parts of eukaryotic cells . the ne is a dynamic structure composed of the outer nuclear membrane ( onm ) and the inner nuclear membrane ( inm ) . the ne is embedded with nuclear pore proteins , through which molecules selectively pass to move between the nucleus and the cytoplasm . the nuclear membranes are bilipid structures supported by a network of proteins . within the nucleus , the inm is underlined by the nuclear lamina , a dynamic filamentous protein network . the nuclear lamina is predominantly composed of lamins , which are dynamically anchored to the inm via posttranslational modifications . the molecular composition of the nuclear lamina has been previously discussed in several reviews [ 1 , 2 ] . in brief , lamins are divided into a- and b - types ( lmna and lmnb , resp . ) and play a central role in the integrity of the nuclear lamina . both proteins bind to the chromatin at highly defined regions , creating a regulatory role for lamina - chromatic interaction . while lmnb is constitutively expressed , the expression of lmna is developmentally regulated , and expression levels differ between cell types . it has , therefore , been suggested that lmna also plays a regulatory role [ 1 , 2 ] . silencing of lmnb causes dramatic changes in the lmna meshwork , while lmna downregulation has no effect on the structural organization of lmnb filaments . this suggests a crucial and indispensable role for lmnb in maintaining the structural integrity of the nuclear lamina . lamins are brought into the inm via a farnesyl group , which is attached to the c - terminus of the molecule by a posttranslational modification . the maturation step of the b - type lamins ends with a farnesylated molecule , while the mature lmna protein is generated after a reversible anchorage to the inm via the farnesylated group . a de novo mutation in the last intron - exon boundary in lmna causes removal of the 3 of exon 11 and a deletion of the c - terminus , including the farnesylation signal . as a result , farnesylation is irreversible , and the progerin protein predominantly attaches to the imn . progerin causes premature cell senescence , which is associated with genome - wide transcriptional changes and telomere shortening [ 6 , 7 ] . progeria patients exhibit premature aging , starting in young children , only a few years old . progerin is also expressed during normal aging [ 6 , 9 ] and during closure of the ductus arteriosus in neonates . in the closing ductus arteriosus the function of progerin in those cells is still obscure , and the mechanism regulating progerin expression in normal physiological situations remains to be studied . next to genetic conditions , a deformed nuclear structure is also found in senescent , aging , and apoptotic cells as well as during cell division [ 1113 ] . moreover , overexpression of lmna in cell culture also causes severe changes in the nuclear shape . in those cells , folding of the nuclear lamina the molecular mechanisms driving the changes in the nuclear lamina in senescent and aging cells are not fully understood . the changes in the nuclear lamina during cell division have , however , been studied extensively and are described in several reviews [ 1 , 4 , 16 ] . in this review , we will focus on the structural changes of the nuclear lamina that are associated with cell senescence and aging . in apoptotic cells , changes in the structure of the nuclear lamina in human mesenchymal stem cells ( hmscs ) precede dna fragmentation , the hallmark of cell apoptosis . this suggests that structural deformation of the nuclear lamina precedes irreversible degradation of lamins during caspase-8 induced apoptosis . changes in the shape of the nuclear lamina also precede well - known bioimaging markers for cell senescence [ 11 , 13 , 17 ] . this suggests that monitoring changes in the nuclear lamina organization could mark early changes in cellular function . architectural changes should , therefore , be investigated in living cells expressing lamins fused to fluorescent proteins . as high overexpression of lamins leads to structural deformation of the nuclear lamina , only cells with low expression level should be considered for analysis of the lamina structure . , analysis can be also performed on three - dimensional reconstructions from immunofluorescence . those are , however , less robust compared with those obtained from living cells . the pixels associated with the nuclear lamina are then identified using automated image processing procedures . several studies reported the quantification of the shape of the cell nucleus in two dimensions [ 19 , 20 ] . those analyses only account for the edge of the nucleus and do not provide an internal architectural description . recently , we developed an automatic method to detect pixels of the nuclear lamina from three - dimensional images . quantitative analysis of the lamina architecture was performed subsequently , resulting in a robust and reliable procedure to study cell populations . the nuclear shape can be described by curvature measures . in conditions where cells exhibit a deformed nuclear shape , as in senescent cells or disease situations , folding of the nuclear lamina is associated with high curvature values and often shows high fluorescence intensity values of lmna , indicating protein accumulation . in young and healthy cells , lmna is evenly distributed along the nuclear rim , and it accumulates mainly in the  short edges  of the nuclear surface . in aging or senescent cells , the main changes in the structure of the nuclear lamina are associated with an uneven distribution of intensity of lmna and folding along the structure ( examples are depicted in figure 1(b ) ) . regions with high intensity values are often surrounded by high curvature values ( figure 1(b ) ) , suggesting a biomechanical association where protein accumulation induces a mechanical pressure that causes bending of the structure . several approaches can be used to quantify the three - dimensional structure of the nuclear lamina . a simple method is quantifying the length - to - width ratio of nuclear objects . structural changes along the lamina would then not be detected , because only the overall length and width of the cell are measured . a more accurate description can be provided by curvature measures of the folding of the structure . the distribution of fluorescence intensity at the nuclear lamina can provide a quantitative description of the structure as well . the intensity distribution can be summarized by the mean value and the skewness of the intensity distribution . absolute curvature and intensity values can not be directly compared between cells ; the measured values should be normalized first . a cell - based accurate and robust description of the nuclear lamina can then be obtained by combining these features . with a linear classification method it is possible to determine whether cell populations can be classified based on the nuclear lamina structure . a comparison between different cell populations is possible , because the measures themselves are normalized . the result of this robust analysis demonstrated that young and aged cell populations can be discriminated based on mean intensity and curvature values of the nuclear lamina ( figure 3 ) . a confined accumulation of proteins is often a result of a decrease in protein mobility . using frap analyses , lmna at the nuclear envelop is more mobile compared to lmnb . in addition , the mobility of progerin is significantly reduced compared to the wild type lmna protein [ 22 , 23 ] . triton treatment of cells disrupts the localization of soluble proteins , and only insoluble proteins and structures that are triton - resistant remain intact . in cells at low passage number , lmna enrichment at the nuclear envelope is significantly lower compared with cells at high passage number ( figure 3 ) . the enrichment in lmna accumulation at the nuclear envelope is significantly more pronounced after triton treatment ( figure 2 ) . this procedure suggests that lmna at the nuclear envelope is less mobile in senescent cells than in young cells . when zooming into the nuclear envelop with the frap procedure , lower lmna mobility was found at regions with high protein accumulation compared with low fluorescence intensity regions . as the high fluorescence regions are mainly localized at bent structures , this suggests that folding of the nuclear lamina is associated with local accumulation of lmna . quantitative analyses of the nuclear lamina show that the mean normalized intensity of lmna decreased from the young to the old and senescent cells . this indicates changes in the lmna distribution in the nuclear lamina during aging and senescence . changes in the average curvature between young cells and senescent and old cells are smaller compared to the intensity ( figure 4 ) . the average curvature increases , however , significantly more in apoptotic cells compared to young or senescent cells . since cell apoptosis is increased in a population of senescent cells , this suggests that a major increase in folding of the nuclear lamina is secondary to an increase in local protein accumulation . regulatory functions of the nuclear lamins have been widely studied , and a dynamic multifunctional role is emerging . lamins directly bind to the chromatin , and chromatin recruitment of the nuclear envelope alters gene expression . how changes in the structure of the lamina contribute to nuclear function in aging cells recent technical advances in monitoring and measuring the dynamics of the nuclear lamina structure [ 15 , 24 , 25 ] and lamina - chromatic dynamics on a single cell resolution   will open new opportunities to further understand how the structure of the nuclear lamina contributes to regulation of nuclear function . based on the quantification of the biophysical features of the nuclear lamina , the following mechanical models are suggested : initially protein mobility decreases , leading to confined and localized lmna accumulation in the nuclear envelop . the local lmna accumulation could result in a mechanical pressure that subsequently results in bending of the structure . when structural pressure of the nuclear lamina would be too large to maintain , the smooth ellipsoidal shape would deform , and the nuclear envelope structure would form an irregular shape . advances in molecular imaging at the single cell level , in combination with high resolution studies of chromatin dynamics , enable the possibility to study how spatial changes of the nuclear lamina affect nuclear function in aging and senescent cells .