Search results for "senescence."
showing 10 items of 335 documents
Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence.
2020
Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C) approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a dis…
Vaccination in old age: Challenges and promises
2021
Abstract Vaccination is one of the most effective medical interventions ever introduced, preventing millions of cases of infections worldwide every year. However, vaccines are commonly believed to be less effective in providing protection in older adults, due to the perceived decline seen in immunity in this population (“immunosenescence”). Accordingly, this chapter considers how to identify hallmarks of immunosenescence and approach their resolution strategically. It was reviewed potential options for therapeutic intervention to restore appropriate responses to vaccines in older adults.
Heat shock proteins may have effects on cellular senescence and may lead to neoplastic transformation
2007
Senescence and p130/Rbl2: a new beginning to the end.
2009
Senescence is the process of cellular aging dependent on the normal physiological functions of non-immortalized cells. With increasing data being uncovered in this field, the complex molecular web regulating senescence is gradually being unraveled. Recent studies have suggested two main phases of senescence, the triggering of senescence and the maintenance of senescence. Each has been supported by data implying precise roles for DNA methyltransferases, reactive oxygen species and other factors. We will first summarize the data supporting these claims and then highlight the specific role that we hypothesize that p130/Rbl2 plays in the modulation of the senescence process.
RASSF1A inhibits estrogen receptor alpha expression and estrogen-independent signalling: implications for breast cancer development
2012
The Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor whose inactivation is implicated in the development of many human cancers, including breast carcinomas. Little is known about the tumor-suppressive function of RASSF1A in breast tissue and whether its inactivation is mechanistically involved in the initiation and progression of breast tumors. Here, we show that RASSF1A inhibits breast cancer growth in vivo, and suppresses estrogen receptor (ERα) expression and function. Reconstitution of RASSF1A in MCF7 cells led to decreased ERα levels and reduced sensitivity to estrogen (E2). Concomitantly, we observed decreased expression of Id1 as well as the E2-responsive gen…
Effects of B-Cell Lymphoma on the Immune System and Immune Recovery after Treatment: The Paradigm of Targeted Therapy
2022
B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune syst…
An immunologist's guide to immunosenescence and its treatment
2022
Abstract Introduction: Aging causes several changes in the immune system, although immune aging is strongly influenced by individual immunological history, as well as genetic and environmental factors leading to inter-individual variability. Areas covered: We focused on the biological and clinical meaning of immunosenescence. SARS-CoV-2 and Yellow Fever vaccine have demonstrated the clinical relevance of immunosenescence, while inconsistent results, obtained from longitudinal studies aimed at looking for immune risk phenotypes, have revealed that immunosenescence is highly context-dependent. Large projects allowed the delineation of the drivers of immune system variance, including genetic a…
How Can We Improve Vaccination Response in Old People? Part I: Targeting Immunosenescence of Innate Immunity Cells
2022
Vaccination, being able to prevent millions of cases of infectious diseases around the world every year, is the most effective medical intervention ever introduced. However, immunosenescence makes vaccines less effective in providing protection to older people. Although most studies explain that this is mainly due to the immunosenescence of T and B cells, the immunosenescence of innate immunity can also be a significant contributing factor. Alterations in function, number, subset, and distribution of blood neutrophils, monocytes, and natural killer and dendritic cells are detected in aging, thus potentially reducing the efficacy of vaccines in older individuals. In this paper, we focus on t…
Effects of 5-Azacitidine on Dnmt2/Trdmt1 expression levels and endoplasmic reticulum stress in cellular models of insulinoma
2021
Diabetes mellitus affects people all over the world of all ages or social groups making it a worldwide healthcare challenge. Moreover, untreated or badly treated diabetes carries a risk of serious complications including premature death (IDF Diabetes Atlas 9th edition, 2019). The main symptom of diabetes is insulin secretion and/or action disorder leading to hyperglycemia what results in impaired carbohydrate, fat, and protein metabolism (“Diagnosis and Classification of Diabetes Mellitus,” 2013). Dnmt2/ Trdmt1 in its structure and sequence is similar to DNA methyltransferases, however, it has been shown that mainly methylates aspartic acid transfer RNA, specifically at the cytosine-38 resi…
Age is not just a number : Mathematical model suggests senescence affects how fish populations respond to different fishing regimes
2021
Senescence is often described as an age-dependent increase in natural mortality (known as actuarial senescence) and an age-dependent decrease in fecundity (known as reproductive senescence), and its role in nature is still poorly understood. Based on empirical estimates of reproductive and actuarial senescence, we used mathematical simulations to explore how senescence affects the population dynamics of Coregonus albula, a small, schooling salmonid fish. Using an empirically based eco-evolutionary model, we investigated how the presence or absence of senescence affects the eco-evolutionary dynamics of a fish population during pristine, intensive harvest, and recovery phases. Our simulation …