The potential longevity-promoting hypoxic-hypercapnic environment as a measure for radioprotection.

Many biological mechanisms of aging well converge with radiation's biological effects. We used scientific insights from the field of aging to establish a novel hypoxic-hypercapnic environment (HHE) concept for radioprotection. According to this concept, HHE which possesses an anti-aging and longevity-promoting potential, should also act as a radiomitigator and radioprotector.

Stem cell-derived extracellular vesicles as senotherapeutics.

Cellular senescence (CS) is recognized as one of the hallmarks of aging, and an important player in a variety of age-related pathologies. Accumulation of senescent cells can promote a pro-inflammatory and pro-cancerogenic microenvironment. Among potential senotherapeutics are extracellular vesicles (EVs) (40-1000 nm), including exosomes (40-150 nm), that play an important role in cell-cell communications.

Correlative links between natural radiation and life expectancy in the US population.

The linear no-threshold (LNT) hypothesis is still the ruling concept which dictates the radiation protection health policy and regulations. However, more and more studies show that not only that low dose radiation pose no danger to our health, but also exhibits clear beneficial health effects. Here, we evaluated the correlative links of the natural sources of radiation-terrestrial radiation (TR), cosmic radiation (CR), and Radon-222, with life expectancy, the most integrative index of population health.

Small molecules for cell reprogramming: a systems biology analysis.

If somatic stem cells would be able to maintain their regenerative capacity over time, this might, to a great extent, resolve rejuvenation issues. Unfortunately, the pool of somatic stem cells is limited, and they undergo cell aging with a consequent loss of functionality. During the last decade, low molecular weight compounds that are able to induce or enhance cell reprogramming have been reported.

Background radiation impacts human longevity and cancer mortality: reconsidering the linear no-threshold paradigm.

The current linear no-threshold paradigm assumes that any exposure to ionizing radiation carries some risk, thus every effort should be made to maintain the exposures as low as possible. We examined whether background radiation impacts human longevity and cancer mortality. Our data covered the entire US population of the 3139 US counties, encompassing over 320 million people.

c-Met as a new marker of cellular senescence.

Here, we reported for the first time an increased expression of c-Met protein in primary cultures of human dermal and pulmonary fibroblasts of late passages. This suggests that c-Met could serve as an early marker of cellular senescence (CS). The levels of c-Met-related signaling proteins phospho-Akt and Stat3 were also increased in (pre)senescent fibroblasts.

Transplantation of mesenchymal stem cells reverses behavioural deficits and impaired neurogenesis caused by prenatal exposure to valproic acid.

Neurodevelopmental impairment can affect lifelong brain functions such as cognitive and social behaviour, and may contribute to aging-related changes of these functions. In the present study, we hypothesized that bone marrow-derived mesenchymal stem cells (MSC) administration may repair neurodevelopmental behavioural deficits by modulating adult hippocampal neurogenesis. Indeed, postnatal intracerebral transplantation of MSC has restored cognitive and social behaviour in mice prenatally exposed to valproic acid (VPA).

Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome.

Purpose: There is evidence that Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) could display some molecular and morphologic markers of cellular senescence (CS). We hypothesized that CS mechanisms may have potential prognostic relevance in cHL and investigated whether the expression of the well-established CS biomarkers p21(CIP1/WAF1) and p16(INK4a) by HRS cells might be predictive of the probability of event-free survival (EFS).

Experimental Design: The study analyzed a retrospective cohort of 147 patients and the results were validated on a cohort of 91 patients independently diagnosed and treated in a different institution.

ShcC proteins: brain aging and beyond.

To date, most studies of Shc family of signaling adaptor proteins have been focused on the near-ubiquitously expressed ShcA, indicating its relevance to age-related diseases and longevity. Although the role of the neuronal ShcC protein is much less investigated, accumulated evidence suggests its importance for neuroprotection against such aging-associated conditions as brain ischemia and oxidative stress. Here, we summarize more than decade of studies on the ShcC expression and function in normal brain, age-related brain pathologies and immune disorders with a focus on the interactions of ShcC with signaling proteins/pathways, and the possible implications of these interactions for changes associated with aging.

Uncovering the geroprotective potential of medicinal plants from the Judea region of Israel.

Plants growing in the Judea region are widely used in traditional medicine. This phytogeographic zone stands out in its climatic conditions and biodiversity. Consequently, both endemic and widely distributed Mediterranean plants growing in the area have unique chemotypes characterized by accumulation of relatively high levels of phytosteroids.

Chronic treatment with anti-bipolar drugs causes intracellular alkalinization in astrocytes, altering their functions.

Bipolar disorder I and II are affective disorders with mood changes between depressive and manic (bipolar I) or hypomanic (bipolar II) periods. Current therapy of these conditions is chronic treatment with one or more of the anti-bipolar drugs, Li(+) ('lithium'), carbamazepine and valproic acid. The pathophysiology of bipolar disorder is multifactorial and far from clear.

Enhanced genetic instability and dasatinib sensitivity in mammary tumor cells lacking NEDD9.

Elevated expression of the NEDD9/HEF1/Cas-L scaffolding protein promotes tumor cell invasion and metastasis in multiple cancer cell types. Conversely, generation of mammary tumors in the mouse mammary tumor virus (MMTV)-polyoma virus middle T (PyVT) genetic model is delayed by a Nedd9(-/-) genotype. These activities arise from the role of NEDD9 in assembling complexes and supporting activity of cancer signaling proteins, including FAK, Src, Shc, and AKT, and would support evaluation of NEDD9 expression as an unambiguous biomarker for tumor aggressiveness.

MicroRNA-regulated protein-protein interaction networks: how could they help in searching for pro-longevity targets?

In spite of enormous efforts and accumulated knowledge, our capabilities for tackling aging and age-related diseases (ARDs), and ultimately to promote longevity, are still very modest. What is lacking--essential data on key players, efficient analytic tools, or both? Here we discuss how the existing data may be integrated and analyzed in the context of microRNA (miRNA)-regulated protein-protein interaction networks. The proposed model highlighted: (1) The strong molecular links between aging, longevity, and ARDs; (2) the possibility and even the preferability of initiating longevity-promoting interventions in adult life; (3) the potentially important role for miRNA- (or small interfering RNA [siRNA]) mediated targeting of certain genes with features of antagonistic pleiotropy; (4) the superiority of systemic interventions to the common single-target approach in curing ARDs and promoting longevity.

Senescing cells share common features with dedifferentiating cells.

Dedifferentiation signifies the capacity of somatic cells to acquire stem cell-like properties. This process can be induced during normal development and as a response to various stimuli, such as pathogen infection and wounding. Dedifferentiation also characterizes the transition of differentiated leaf cells into protoplasts (plant cells devoid of cell walls), a transition accompanied by widespread chromatin decondensation.

NEDD9 promotes oncogenic signaling in mammary tumor development.

In the past 3 years, altered expression of the HEF1/CAS-L/NEDD9 scaffolding protein has emerged as contributing to cancer metastasis in multiple cancer types. However, whereas some studies have identified elevated NEDD9 expression as prometastatic, other work has suggested a negative role in tumor progression. We here show that the Nedd9-null genetic background significantly limits mammary tumor initiation in the MMTV-polyoma virus middle T genetic model.

The signaling hubs at the crossroad of longevity and age-related disease networks.

The established human age-related disease proteins (ARDPs) and longevity-associated proteins (LAPs) together with their first-order interacting partners form scale-free networks which significantly overlap. About half of the common proteins are involved in signal transduction. These proteins are strongly interconnected and in turn form a common signaling network which comprises over 40% of all hubs (proteins with multiple interactions) in the human interactome.

Modified pectin-based carrier for gene delivery: cellular barriers in gene delivery course.

The use of polysaccharides as DNA carriers has high potential for gene therapy applications. Pectin is a structural plant polysaccharide heterogeneous with respect to its chemical structure. It contains branches rich in galactose residues which serve as potential ligands for membrane receptors interaction.

Common gene signature of cancer and longevity.

An association between aging/longevity and cancer has long been suggested, yet the evolutionary and molecular links between these complicated traits remain elusive. Here, we analyze the relationship between longevity- and cancer-associated genes/proteins (LAGs/LAPs and CAGs/CAPs, respectively). Specifically, we address the following questions: (1) to what extent the CAGs and LAGs are evolutionary conserved and how they (or their orthologs) are related to each other in diverse species? (2) Could they act in cooperative manner at a protein level via protein-protein interactions (PPIs) and, if so, by forming a PPI network? We found that (i) the common genes (both LAGs and CAGs) show the same remarkable trend from yeast to humans: tumor suppressors are associated with lifespan extension, whereas the oncogenes are associated with reduced lifespan; (ii) LAPs and CAPs have a significantly higher average connectivity than other proteins in the human interactome; and (iii) LAPs and CAPs may act in cooperative manner via numerous direct and indirect PPIs between themselves and eventually by forming a PPI network.

[Cadherins in malignancies of the female genital tract].

Cadherins are a superfamily of adhesion molecules that mediate Ca++ -dependent cell-cell adhesion necessary for normal morphogenesis and maintenance of tissue integrity. A classical cadherin molecule, such as E-cadherin, is a glycoprotein made up of three parts: an extracellular portion composed of five identical domains, a transmembrane portion composed of a single domain and a cytoplasmic portion composed of two domains. The cytoplasmic portion is anchored by means of cytoplasmic catenins to the cytoskeleton.

p66ShcA and ageing: modulation by longevity-promoting agent aurintricarboxylic acid.

Many mutations that extend the lifespan of the lower organisms such as C. elegans and Drosophila, are associated with signaling or apoptotic pathways. Recently, such a possibility was shown in mammals: p66ShcA-deficient mice were more resistant to oxidative stress and lived longer than the wild-type animals [Migliaccio, E.