Lamin A K97E leads to NF-κB-mediated dysfunction of inflammatory responses in dilated cardiomyopathy.

BACKGROUND INFORMATION: Lamins are type V intermediate filament proteins underlying the inner nuclear membrane which provide structural rigidity to the nucleus, tether the chromosomes, maintain nuclear homeostasis, and remain dynamically associated with developmentally regulated regions of the genome. A large number of mutations particularly in the LMNA gene encoding lamin A/C results in a wide array of human diseases, collectively termed as laminopathies. Dilated Cardiomyopathy (DCM) is one such laminopathic cardiovascular disease which is associated with systolic dysfunction of left or both ventricles leading to cardiac arrhythmia which ultimately culminates into myocardial infarction. RESULTS: In this work, we have unraveled the epigenetic landscape to address the regulation of gene expression in mouse myoblast cell line in the context of the missense mutation LMNA 289A

Characterization of the Secretome, Transcriptome, and Proteome of Human ß Cell Line EndoC-ßH1.

Early diabetes research is hampered by limited availability, variable quality, and instability of human pancreatic islets in culture. Little is known about the human ß cell secretome, and recent studies question translatability of rodent ß cell secretory profiles. Here, we verify representativeness of EndoC-ßH1, one of the most widely used human ß cell lines, as a translational human ß cell model based on omics and characterize the EndoC-ßH1 secretome. We profiled EndoC-ßH1 cells using RNA-seq, data-independent acquisition, and tandem mass tag proteomics of cell lysate. Omics profiles of EndoC-ßH1 cells were compared to human ß cells and insulinomas. Secretome composition was assessed by data-independent acquisition proteomics. Agreement between EndoC-ßH1 cells and primary adult human ß cells was ∼90% for global omics profiles as well as for ß cell markers, transcription factors, and enzymes. Discrepancies in expression were due to elevated proliferation rate of EndoC-ßH1 cells compared to adult ß cells. Consistently, similarity was slightly higher with benign nonmetastatic insulinomas. EndoC-ßH1 secreted 783 proteins in untreated baseline state and 3135 proteins when stressed with nontargeting control siRNA, including known ß cell hormones INS, IAPP, and IGF2. Further, EndoC-ßH1 secreted proteins known to generate bioactive peptides such as granins and enzymes required for production of bioactive peptides. EndoC-ßH1 secretome contained an unexpectedly high proportion of predicted extracellular vesicle proteins. We believe that secretion of extracellular vesicles and bioactive peptides warrant further investigation with specialized proteomics workflows in future studies.

Proprotein convertase PCSK9 affects expression of key surface proteins in human pancreatic beta cells via intracellular and extracellular regulatory circuits.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in the degradation of the low-density lipoprotein receptor. PCSK9 also targets proteins involved in lipid metabolism (very low-density lipoprotein receptor), immunity (major histocompatibility complex I), and viral infection (cluster of differentiation 81). Recent studies have also indicated that PCSK9 loss-of-function mutations are associated with an increased incidence of diabetes; however, the expression and function of PCSK9 in insulin-producing pancreatic beta cells remain unclear. Here, we studied PCSK9 regulation and function by performing loss- and gain-of-function experiments in the human beta cell line EndoC-ßH1. We demonstrate that PCSK9 is expressed and secreted by EndoC-ßH1 cells. We also found that PCSK9 expression is regulated by cholesterol and sterol regulatory element-binding protein transcription factors, as previously demonstrated in other cell types such as hepatocytes. Importantly, we show that PCSK9 knockdown using siRNA results in deregulation of various elements of the transcriptome, proteome, and secretome, and increases insulin secretion. We also observed that PCSK9 decreases low-density lipoprotein receptor and very low-density lipoprotein receptor levels via an extracellular signaling mechanism involving exogenous PCSK9, as well as levels of cluster of differentiation 36, a fatty acid transporter, through an intracellular signaling mechanism. Finally, we found that PCSK9 regulates the cell surface expression of PDL1 and HLA-ABC, proteins involved in cell-lymphocyte interaction, also via an intracellular mechanism. Collectively, these results highlight PCSK9 as a regulator of multiple cell surface receptors in pancreatic beta cells.

Development of geographic inequality in dental caries and its association with socioeconomic factors over an 18-year period in Denmark.

BACKGROUND: Few studies have examined the development of geographic and socioeconomic inequalities in caries over time or have simultaneously assessed individual-level socioeconomic position (SEP) and neighborhood-level factors as a multi-layered phenomenon influencing caries inequalities. This study examined (i) the trends in geographic inequalities in caries among adolescents in Denmark and (ii) how the association between SEP and caries has progressed over time, when accounting for individual and neighborhood-level confounding factors. METHODS: This nationwide repeated cross-sectional study included 15-year-olds in Denmark from 1995, 2003, and 2013 (n = 149,808). The outcome was caries experience (measured by the decayed, missing, and filled tooth surfaces [DMFS] index). The exposure of interest was SEP, indicated by the previous year's parental education, occupational social class, and (equivalized) disposable household income. Covariates included individual-level factors (immigration status, country of origin, number of children and persons in the family, and household type) and neighborhood (residence municipality)-level factors (Gini index; proportion of unemployed, low-educated, and unmarried/non-cohabiting individuals; proportion of single-parent households and households with overcrowding). Data sources included the Danish national dental and administrative social registers and Statistics Denmark's statistics database (StatBank). Data were analyzed using spatial and spatiotemporal modelling utilizing zero-inflated negative binomial regressions and integrated nested Laplace approximations for Bayesian parametric inference. Observed caries experience geo-maps of the Danish municipalities for 1995, 2003, and 2013 were created. RESULTS: Between 1995 and 2013, caries prevalence in the 15-year-olds declined sharply (1995, 71%; 2013, 45%). Caries experience declined in nearly all socioeconomic subgroups and municipalities. However, geographic inequalities persisted with higher caries levels largely concentrated in the relatively deprived areas of Denmark. Increasing relative socioeconomic inequalities in caries over time were observed with significant graded associations between SEP and caries despite adjustment for the various individual and neighborhood-level covariates and the effect of assessment year (e.g., 15-year-olds with parents having basic education had 1.91-fold [95% CI: 1.86-1.95] higher caries experience than those having parents with high education). CONCLUSIONS: Reducing these enduring inequalities will likely require additional resources and targeted supportive and preventive measures for adolescents from lower SEP backgrounds and those residing in municipalities with higher caries prevalence.

Emerging roles of lamins and DNA damage repair mechanisms in ovarian cancer.

Lamins are type V intermediate filament proteins which are ubiquitously present in all metazoan cells providing a platform for binding of chromatin and related proteins, thereby serving a wide range of nuclear functions including DNA damage repair. Altered expression of lamins in different subtypes of cancer is evident from researches worldwide. But whether cancer is a consequence of this change or this change is a consequence of cancer is a matter of future investigation. However changes in the expression levels of lamins is reported to have direct or indirect association with cancer progression or have regulatory roles in common neoplastic symptoms like higher nuclear deformability, increased genomic instability and reduced susceptibility to DNA damaging agents. It has already been proved that loss of A type lamin positively regulates cathepsin L, eventually leading to degradation of several DNA damage repair proteins, hence impairing DNA damage repair pathways and increasing genomic instability. It is established in ovarian cancer, that the extent of alteration in nuclear morphology can determine the degree of genetic changes and thus can be utilized to detect low to high form of serous carcinoma. In this review, we have focused on ovarian cancer which is largely caused by genomic alterations in the DNA damage response pathways utilizing proteins like RAD51, BRCA1, 53BP1 which are regulated by lamins. We have elucidated the current understanding of lamin expression in ovarian cancer and its implications in the regulation of DNA damage response pathways that ultimately result in telomere deformation and genomic instability.

Depression symptoms and recurrent aphthous stomatitis-Evidence from a population-based study in Indonesia.

OBJECTIVES: This study aims to report the prevalence and distribution of recurrent aphthous stomatitis (RAS) among Indonesian adults and to test the relationship between symptom of depression and RAS. METHODS: Data from the 2007 Indonesia Family Life Survey (IFLS 2007) were analysed to assess the association between symptom of depression and RAS. The prevalence of RAS in the previous month was self-reported. Symptom of depression was measured using the 10-item Center for Epidemiologic Studies Depression (CES-D) scale. The distribution of RAS according to age, sex and level of stress was also presented in the bivariate analysis. Multivariable logistic regression models were fitted to test associations between symptom of depression and RAS, controlling for age, sex and the stress level. RESULTS: The previous month prevalence of RAS in Indonesian population was 12%. The adjusted odds ratios (ORs) from the logistic regression models indicate that, for each unit increase in the CES-D depression score (range: 0-30), there was a 9% increase in the odds of having RAS (OR: 1.09, 95%CI: 1.08-1.10). Being older and being male was related with lower prevalence of RAS. CONCLUSIONS: A higher score of depression was related to a higher prevalence of RAS. This association was persistent even after controlling for age, sex and the level of stress.

Utilization of etoricoxib in dental patients in the Nordic countries: a population-based register study.

Background: Etoricoxib is a second-generation cyclooxygenase-2-inhibitor approved in 2012 for short-term treatment of pain associated with dental surgery. Objectives: To evaluate etoricoxib utilization in dental patients in the Nordic countries, including its off-label use. Methods: The entire populations of Denmark, Finland, Sweden and Norway with etoricoxib prescriptions written by dentists and dispensed in 2012-2014 were evaluated using national register data. Nationwide estimates of etoricoxib utilization were generated according to year, gender, age, dose and package size. Off-label use in paediatric patients, prescribed doses >90 mg/day or for dental contacts not associated with surgical procedures, and concomitant administration with anticoagulants were evaluated. Results: Utilization of etoricoxib for dental pain was low (1615 prescriptions: Finland, 907; Sweden, 359; Norway, 337; Denmark, 12). Overall, 70% of the prescriptions were without an associated dental procedure. Moreover, 58%, 55%, 10% and 58% of the prescriptions in Denmark, Finland, Sweden and Norway, respectively, were for >90 mg/day doses. Few paediatric prescriptions were dispensed (n < 10), and only a small overlap (n = 21) was observed between etoricoxib and anticoagulant prescriptions. Conclusions: Given the low overall number of prescriptions, it is unlikely that off-label use of etoricoxib within dentistry in the Nordic countries is an important public health concern.

Single-chip source-free terahertz spectroscope across 0.04-0.99 THz: combining sub-wavelength near-field sensing and regression analysis.

This paper demonstrates a methodology to miniaturize THz spectroscopes into a single silicon chip by eliminating traditional solid-state architectural components such as complex tunable THz and optical sources, nonlinear mixing and amplifiers. The proposed method achieves this by extracting incident THz spectral signatures from the surface of an on-chip antenna itself. The information is sensed through the spectrally-sensitive 2D distribution of the impressed current surface under the THz incident field. By converting the antenna from a single-port to a massively multi-port architecture with integrated electronics and deep subwavelength sensing, THz spectral estimation is converted into a linear estimation problem. We employ rigorous regression techniques and analysis to demonstrate a single silicon chip system operating at room temperature across 0.04-0.99 THz with 10 MHz accuracy in spectrum estimation of THz tones across the entire spectrum.

Changes in the Nuclear Envelope in Laminopathies.

Double-membrane-bound nucleus is the major organelle of every metazoan cell, which controls various nuclear processes like chromatin maintenance, DNA replication, transcription and nucleoskeleton-cytoskeleton coupling. Nuclear homeostasis depends on the integrity of nuclear membrane and associated proteins. Lamins, underlying the inner nuclear membrane (INM), play a crucial role in maintaining nuclear homeostasis. In this review, we have focussed on the disruption of nuclear homeostasis due to lamin A/C mutation which produces a plethora of diseases, termed as laminopathies.

DCM associated LMNA mutations cause distortions in lamina structure and assembly.

BACKGROUND: A and B-type lamins are integral scaffolding components of the nuclear lamina which impart rigidity and shape to all metazoan nuclei. Over 450 mutations in A-type lamins are associated with 16 human diseases including dilated cardiomyopathy (DCM). Here, we show that DCM mutants perturb the self-association of lamin A (LA) and it's binding with lamin B1 (LB1). METHODS: We used confocal and superresolution microscopy (NSIM) to study the effect of LA mutants on the nuclear lamina. We further used circular dichroism, fluorescence spectroscopy and isothermal titration calorimetry (ITC) to probe the structural modulations, self-association and heteropolymeric association of mutant LA. RESULTS: Transfection of mutants in cultured cell lines result in the formation of nuclear aggregates of varied size and distribution. Endogenous LB1 is sequestered into these aggregates. This is consistent with the ten-fold increase in association constant of the mutant proteins compared to the wild type. These mutants exhibit differential heterotypic interaction with LB1, along with significant secondary and tertiary structural alterations of the interacting proteins. Thermodynamic studies demonstrate that the mutants bind to LB1 with different stoichiometry, affinity and energetics. CONCLUSIONS: In this report we show that increased self-association propensity of mutant LA modulates the LA-LB1 interaction and precludes the formation of an otherwise uniform laminar network. GENERAL SIGNIFICANCE: Our results might highlight the role of homotypic and heterotypic interactions of LA in the pathogenesis of DCM and hence laminopathies in the broader sense.

Characterization of unfolding mechanism of human lamin A Ig fold by single-molecule force spectroscopy-implications in EDMD.

A- and B-type lamins are intermediate filament proteins constituting the nuclear lamina underneath the nuclear envelope thereby conferring proper shape and mechanical rigidity to the nucleus. Lamin proteins are also shown to be related diversely to basic nuclear processes. More than 400 mutations in human lamin A protein alone have been reported to produce at least 11 different disease conditions jointly termed as laminopathies. These mutations in lamin A are scattered throughout its helical rod domain, as well as the C-terminal domain containing the conserved Ig-fold region. The commonality of phenotypes in all these diseases is characterized by misshapen nuclei of the affected tissues which might stem from altered rigidity of the supporting lamina hence lamins. Here we have focused on autosomal dominant Emery-Dreifuss Muscular Dystrophy, one such laminopathy where R453W is the causative mutation located in the Ig domain of lamin A. We have investigated by single-molecule force spectroscopy how a stretching mechanical perturbation senses the destabilizing effect of the mutation in the lamin A Ig domain and compared the mechanoelastic properties of the mutant R453W with that of the wild-type in conjunction with steered molecular dynamics. Furthermore, we have shown the interaction of Ig domain with emerin, another key player and interacting partner in the pathogenesis of EDMD, is disrupted in the R453W mutant. This altered mechanoresistance of Ig domain itself and consequent uncoupling of lamin A-emerin interaction might underlie the altered mechanotransduction properties of EDMD affected nuclei.

High Sensitivity and High Throughput Magnetic Flow CMOS Cytometers with 2D Oscillator Array and Inter-Sensor Spectrogram Cross-correlation.

In the paper, we present an integrated flow cytometer with a 2D array of magnetic sensors based on dual-frequency oscillators in a 65-nm CMOS process, with the chip packaged with microfluidic controls. The sensor architecture and the presented array signal processing allows uninhibited flow of the sample for high throughput without the need for hydrodynamic focusing to a single sensor. To overcome the challenge of sensitivity and specificity that comes as a trade off with high throughout, we perform two levels of signal processing. First, utilizing the fact that a magnetically tagged cell is expected to excite sequentially an array of sensors in a time-delayed fashion, we perform inter-site cross-correlation of the sensor spectrograms that allows us to suppress the probability of false detection drastically, allowing theoretical sensitivity reaching towards sub-ppM levels that is needed for rare cell or circulating tumor cell detection. In addition, we implement two distinct methods to suppress correlated low frequency drifts of singular sensors-one with an on-chip sensor reference and one that utilizes the frequency dependence of the susceptibility of super-paramagnetic magnetic beads that we deploy as tags. We demonstrate these techniques on a 7×7 sensor array in 65 nm CMOS technology packaged with microfluidics with magnetically tagged dielectric particles and cultu lymphoma cancer cells.

Dentin-derived alveolar bone graft for alveolar augmentation: A systematic review.

Introduction: Application of alveolar bone graft (ABG) in alveolar augmentation is done to prevent excessive bone resorption due to tooth extraction, missing teeth, or other diseases/conditions affecting the alveolar bone. The use of autogenous dentin-derived ABG has been considered as the composition of dentin appears to be nearly analogous to that of bone. Objective: This systematic review aims to assess the efficacy of dentin-derived ABG for alveolar augmentation of post-extraction sockets or other alveolar bone defects by evaluating volume gain and histomorphometric data. Material and methods: A search of systematic literature was conducted in Pubmed, Scopus, Web of Science, and Embase from database inception to October 2023. The review included both randomized controlled trials (RCT), pilot studies, clinical trials, and retrospective studies reporting on dentin-derived ABG use for alveolar augmentation. Results: Overall, 298 articles were obtained from the initial search. From these articles, 21 articles met the inclusion criteria and were included for descriptive analysis. All of the studies indicated low risk of bias. Studies of dentin-derived ABG, which used bone-derived grafts as the control group, have shown significantly higher percentages of new bone formation, gain in vertical and horizontal dimensions, and less reduction in dimensions. Conclusions: Dentin-derived ABG was effective in volume maintenance, indicating promising results via histomorphometric and radiographic analysis.

Structural alterations of Lamin A protein in dilated cardiomyopathy.

Lamin A protein, encoded by the LMNA gene, belongs to the type V intermediate filament protein family and is a major nuclear protein component of higher metazoan organisms, including humans. Lamin A along with B-type lamins impart structural rigidity to the nucleus by forming a lamina that is closely apposed to the inner nuclear membrane and is also present as a filamentous network in the interior of the nucleus. A vast number of mutations that lead to a diverse array of at least 11 diseases in humans, collectively termed laminopathies, are being gradually uncovered in the LMNA gene. Dilated cardiomyopathy (DCM) is one such laminopathy in which ventricular dilation leads to an increase in systolic and diastolic volumes, resulting in cardiac arrhythmia and ultimately myocardial infarction. The point mutations in lamin A protein span the entire length of the protein, with a slight preponderance in the central α-helical coiled-coil forming domain. In this work, we have focused on three such important mutations that had been previously observed in DCM-afflicted patients producing severe symptoms. This is the first report to show that these mutations entail significant alterations in the secondary and tertiary structure of the protein, hence perturbing the intrinsic self-association behavior of lamin A protein. Comparison of the enthalpy changes accompanying the deoligomerization process for the wild type and the mutants suggests a difference in the energetics of their self-association. This is further corroborated by the formation of the aggregates of different size and distribution formed inside the nuclei of transfected cells.

Elevated Levels of Lamin A Promote HR and NHEJ-Mediated Repair Mechanisms in High-Grade Ovarian Serous Carcinoma Cell Line.

Extensive research for the last two decades has significantly contributed to understanding the roles of lamins in the maintenance of nuclear architecture and genome organization which is drastically modified in neoplasia. It must be emphasized that alteration in lamin A/C expression and distribution is a consistent event during tumorigenesis of almost all tissues of human bodies. One of the important signatures of a cancer cell is its inability to repair DNA damage which befalls several genomic events that transform the cells to be sensitive to chemotherapeutic agents. This genomic and chromosomal instability is the most common feature found in cases of high-grade ovarian serous carcinoma. Here, we report elevated levels of lamins in OVCAR3 cells (high-grade ovarian serous carcinoma cell line) in comparison to IOSE (immortalised ovarian surface epithelial cells) and, consequently, altered damage repair machinery in OVCAR3. We have analysed the changes in global gene expression as a sequel to DNA damage induced by etoposide in ovarian carcinoma where lamin A is particularly elevated in expression and reported some differentially expressed genes associated with pathways conferring cellular proliferation and chemoresistance. We hereby establish the role of elevated lamin A in neoplastic transformation in the context of high-grade ovarian serous cancer through a combination of HR and NHEJ mechanisms.

Doing science together: Gaining momentum from long-term explorative university-industry research programs.

'Doing science together' collaborations are a more intense form of university-industry interactions and are characterized by a mutual involvement and active participation of academic and company scientists in scientific research. Here, we examine the successful approach that AstraZeneca and its internationally renowned academic partners, Karolinska Institutet and Uppsala University, implemented to fully unlock the potential of all parties in long-term, explorative, truly collaborative research programs. The underlying premises of these successful research programs are three collaborative governance mechanisms (3MCs) that are required that leverage the strengths of each organization: mutual collaboration; mutually beneficial science; and a mutual governance model with senior management involvement.

An Ingestible Pill With CMOS Fluorescence Sensor Array, Bi-Directional Wireless Interface and Packaged Optics for in-Vivo Bio-Molecular Sensing.

The article presents for the first time a pill-based ingestible electronics with CMOS integrated multiplexed fluorescence bio-molecular sensor arrays, bi-directional wireless communication and packaged optics in a FDA-approved capsule for in-vivo bio-molecular sensing. The silicon chip integrates both the sensor array, and the ultra-low-power (ULP) wireless system that allows offloading sensor computing to an external base station that can reconfigure the sensor measurement time, and its dynamic range, allowing optimized high sensitivity measurement under low power consumption. The integrated receiver achieves -59 dBm receiver sensitivity dissipating 121 µW of power. The integrated transmitter operates in a dual mode FSK/OOK delivering -15 dBm of power. The 15-pixel fluorescence sensor array follows an electronic-optic co-design methodology and integrates the nano-optical filters with integrated sub-wavelength metal layers that achieves high extinction ratio (39 dB), thereby eliminating the need for bulky external optical filters. The chip integrates photo-detection circuitry and on-chip 10-bit digitation, and achieves measured sensitivity of 1.6 attomoles of fluorescence labels on surface, and between 100 pM to 1 nM of target DNA detection limit per pixel. The complete package includes a CMOS fluorescent sensor chip with integrated filter, a prototyped UV LED and optical waveguide, functionalized bioslip, off-chip power management and Tx/Rx antenna that fits in a standard FDA approved capsule size 000.

Demographic and economic correlates of health security in West Sumatra province - Indonesia.

OBJECTIVES: Access to health insurances could indicate the degree of health security among communities. Indonesia made a commitment to attain universal health insurance coverage by the end of 2019. However, until today it has not reached the goal of 100% coverage. Therefore, there is a need to portray the demographic and economic correlates of health insurance coverage in an area to improve health security achievement. METHODS: This secondary analysis was based on the 2017 Indonesian national socio-economic survey conducted in the West Sumatra province. Multivariable models using logistic regression were used to estimate the odds ratios (OR) for being uninsured. RESULTS: The results showed that health security, in terms of insurance coverage, was influenced by demographic and economic factors. Young and middle-aged individuals were more likely to be uninsured than older ones (OR = 1.49 and OR = 1.21, respectively). People from a lower educated family, or with lower consumption per capita have higher risk of being uninsured (OR = 3.00 and OR = 1.26, respectively). CONCLUSION: Insurance coverage was influenced by demographic and economic factors. Policymakers should consider demographic and economic factors related to the implementation of universal health coverage. Campaign about the importance of universal health coverage should reach all citizens.

Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase.

BACKGROUND: A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate whether such patients with CU with IgE against TPO benefit from treatment with omalizumab, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. OBJECTIVES: We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had persistent symptoms (wheals and pruritus) despite standard antihistamine therapy were randomized to receive either omalizumab (75-375 mg, dose determined by using the approved asthma dosing table) or placebo subcutaneously once every 2 or 4 weeks for 24 weeks. The primary end point was the change from baseline in mean weekly urticaria activity score after 24 weeks of treatment, as calculated from patients' diaries. The safety and tolerability of omalizumab were also assessed. RESULTS: Of the 49 randomized patients (omalizumab, n = 27; placebo, n = 22), 42 completed the study. At week 24, patients demonstrated a mean reduction in the weekly urticaria activity score from baseline of 17.8 with omalizumab and 7.9 with placebo (P = .0089). Complete protection from wheal development was observed in 19 (70.4%) patients in the omalizumab group compared with only 1 (4.5%) patient in the placebo group. The rate of adverse events was similar in both groups. CONCLUSIONS: The results of this study indicate that omalizumab is an effective treatment option for patients with CU with IgE autoantibodies against TPO who are refractory to conventional treatment.

Lamin A and telomere maintenance in aging: Two to Tango.

Lamin proteins which constitute the nuclear lamina in almost all higher eukaryotes, are mainly of two types A & B encoded by LMNA and LMNB1/B2 genes respectively. While lamin A remains the principal product of LMNA gene, variants like lamin C, C2 and A∆10 are also formed as alternate splice products. Role of lamin A in aging has been highlighted in recent times due to its association with progeroid or premature aging syndromes which is classified as a type of laminopathy. Progeria caused by accelerated accumulation of lamin A Δ50 or progerin occurs due to a mutation in this LMNA gene leading to defects in post translational modification of lamin A. One of the most common and severe symptoms of progeroid laminopathy is accelerated cellular senescence or aging along with bone resorption, muscle weakness, lipodystrophy and cardiovascular disorders. On the other hand, progerin accumulation and telomere dysfunction merge as common traits in the process of chronological aging. Two major hallmarks of physiological aging in humans include loss of genomic integrity and telomere attrition which can result from defective laminar organization leading to deformed nuclear architecture and culminates into replicative senescence. This also adversely affects epigenetic landscape, mitochondrial dysfunction and several signalling pathways like DNA repair, mTOR, MAPK, TGFß. In this review, we discuss the telomere-lamina interplay in the context of physiological aging and progeria.