Lamin A involvement in ageing processes

Cenni, Vittoria; Capanni, Cristina; Mattioli, Elisabetta; Schena, Elisa; Squarzoni, Stefano; Bacalini, Maria Giulia; Garagnani, Paolo; Salvioli, Stefano; Franceschi, Claudio; Lattanzi, Giovanna

doi:10.1016/j.arr.2020.101073

Cited by 60 publications

(68 citation statements)

References 178 publications

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“…Cell intrinsic and cell-independent mechanisms play a synergistic role in HGPS pathogenesis (Bidault et al, 2020;Del Campo et al, 2019;Cenni et al, 2020;Kreienkamp et al, 2016Kreienkamp et al, , 2018Kreienkamp et al, , 2019Kreienkamp & Gonzalo, 2020;Osmanagic-Myers et al, 2019). Thus, an efficient therapeutic strategy needs to counteract both mechanism types.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐6 neutralization ameliorates symptoms in prematurely aged mice

et al. 2021

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Hutchinson–Gilford progeria syndrome (HGPS) causes premature aging in children, with adipose tissue, skin and bone deterioration, and cardiovascular impairment. In HGPS cells and mouse models, high levels of interleukin‐6, an inflammatory cytokine linked to aging processes, have been detected. Here, we show that inhibition of interleukin‐6 activity by tocilizumab, a neutralizing antibody raised against interleukin‐6 receptors, counteracts progeroid features in both HGPS fibroblasts and LmnaG609G/G609G progeroid mice. Tocilizumab treatment limits the accumulation of progerin, the toxic protein produced in HGPS cells, rescues nuclear envelope and chromatin abnormalities, and attenuates the hyperactivated DNA damage response. In vivo administration of tocilizumab reduces aortic lesions and adipose tissue dystrophy, delays the onset of lipodystrophy and kyphosis, avoids motor impairment, and preserves a good quality of life in progeroid mice. This work identifies tocilizumab as a valuable tool in HGPS therapy and, speculatively, in the treatment of a variety of aging‐related disorders.

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Section: Discussionmentioning

confidence: 99%

Interleukin‐6 neutralization ameliorates symptoms in prematurely aged mice

et al. 2021

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“…The Lamin A protein is an integral part of the nuclear membrane, and by lying there could contribute to the special organization of the chromatin, that as proposed, could be an epigenetic information container (see Table 1). A single point mutation in Lamin A protein could therefore imply a sudden disorganization of nuclear architecture, characteristics that has been shown to happen in ageing and in particular to HGPS affected cells (Cenni et al, 2020;Reddy et al, 2020;Liu et al, 2011), and creating a quick information loss that could explain the premature manifestation of ageing phenotypes in HGPS patients.…”

Section: Experimental Observations In Accordance With the Proposed Modelmentioning

confidence: 99%

The Principle of Continuous Biological Information Flow as the Fundamental Foundation for the Biological Sciences. Implications for Ageing Research

Marsellach¹

2020

Preprint

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The current state of biological knowledge contains an unresolved paradox: life as a continuity in the face of the phenomena of ageing. In this manuscript I propose a theoretical framework that offers a solution for this apparent contradiction. The framework proposed is based on a rethinking of what ageing is at a molecular level, as well as on a rethinking of the mechanisms in charge of the flow of information from one generation to the following ones. I propose an information-based conception of ageing instead of the widely accepted damage-based conception of ageing and propose a full recovery of the chromosome theory of inheritance to describe the intergenerational flow of information. Altogether the proposed framework allows a precise and unique definition of what life is: a continuous flow of biological information. The proposed framework also implies that ageing is merely a consequence of the way in which epigenetically-coded phenotypic characteristics are passed from one generation to the next ones.

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“…The consequences of the failure of mechanisms to maintain genome stability are vividly illustrated by the pathological patterns of numerous accelerated asging syndromes that are caused by mutations in DNA repair genes (for example, Werner, Cocaine, Bloom syndromes, xeroderma pigmentosum, ataxia-telangiectasia, and others) and nuclear architecture maintenance genes (laminopathy, in particular, Hutchinson–Gilford syndrome) [ 6 , 7 , 8 , 9 , 10 ]. On the other hand, an increased expression of a number of genes, providing a response to DNA damage and repair, causes an increase in the lifespan of model animals [ 2 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

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Lamin A involvement in ageing processes

Cited by 60 publications

References 178 publications

Interleukin‐6 neutralization ameliorates symptoms in prematurely aged mice

Interleukin‐6 neutralization ameliorates symptoms in prematurely aged mice

The Principle of Continuous Biological Information Flow as the Fundamental Foundation for the Biological Sciences. Implications for Ageing Research

Genome-Protecting Compounds as Potential Geroprotectors

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