Zhavoronkov A.,United Information Technology |
Smit-Mcbride Z.,University of California at Davis |
Guinan K.J.,Biogerontology Research Foundation |
Guinan K.J.,BioAtlantis |
And 3 more authors.
Journal of Molecular Medicine | Year: 2012
Scientific understanding of the genetic components of aging has increased in recent years, with several genes being identified as playing roles in the aging process and, potentially, longevity. In particular, genes encoding components of the nuclear lamina in eukaryotes have been increasingly well characterized, owing in part to their clinical significance in age-related diseases. This review focuses on one such gene, which encodes lamin A, a key component of the nuclear lamina. Genetic variation in this gene can give rise to lethal, early-onset diseases known as laminopathies. Here, we analyze the literature and conduct computational analyses of lamin A signaling and intracellular interactions in order to examine potential mechanisms for altering or slowing down aberrant Lamin A expression and/or for restoring the ratio of normal to aberrant lamin A. The ultimate goal of such studies is to ameliorate or combat laminopathies and related diseases of aging, and we provide a discussion of current approaches in this review. © 2012 The Author(s).
Marciano B.E.,National Institute of Allergy and Infectious Diseases |
Huang C.-Y.,National Institute of Allergy and Infectious Diseases |
Joshi G.,National Institute of Allergy and Infectious Diseases |
Rezaei N.,Tehran University of Medical Sciences |
And 52 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014
Background Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. Objectives We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. Methods An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Results Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≥1 month) showed an increased prevalence of complications (P =.006) and death caused by BCG-associated complications (P <.0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P =.001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P<.0001). Conclusions BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications. © 2013 American Academy of Allergy, Asthma & Immunology.
Danilov A.,RAS Engelhardt Institute of Molecular Biology |
Shaposhnikov M.,Syktyvkar State University |
Shevchenko O.,Russian Academy of Sciences |
Zemskaya N.,Russian Academy of Sciences |
And 2 more authors.
Oncotarget | Year: 2015
Most age-related diseases and aging itself are associated with chronic inflammation. Thus pharmacological inhibition of inflammatory processes may be effective antiaging strategy. In this study we demonstrated that treatment of Drosophila melanogaster with 10 non-steroidal anti-inflammatory drugs (NSAIDs: CAY10404, aspirin, APHS, SC-560, NS-398, SC-58125, valeroyl salicylate, transresveratrol, valdecoxib, licofelone) leads to extension of lifespan, delays age-dependent decline of locomotor activity and increases stress resistance. The effect of the lifespan increase was associated with decrease of fecundity. Depending on the concentration, NSAIDs demonstrated both anti- and pro-oxidant properties in Drosophila tissues. However, we failed to identify clear correlation between antioxidant properties of NSAIDs and their pro-longevity effects. The lifespan extending effects of APHS, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, and licofelone were more pronounced in males, valdecoxib and aspirin - in females. We demonstrated that lifespan extension effect of NSAIDs was abolished in flies with defective genes involved in Pkh2-ypk1-lem3-tat2 pathway.
Moskalev A.A.,Russian Academy of Sciences |
Shaposhnikov M.V.,Russian Academy of Sciences |
Plyusnina E.N.,Russian Academy of Sciences |
Zhavoronkov A.,Center for Pediatric Hematology |
And 4 more authors.
Ageing Research Reviews | Year: 2013
Since the first publication on Somatic Mutation Theory of Aging (Szilárd, 1959), a great volume of knowledge in the field has been accumulated. Here we attempted to organize the evidence "for" and "against" the hypothesized causal role of DNA damage and mutation accumulation in aging in light of four Koch-like criteria. They are based on the assumption that some quantitative relationship between the levels of DNA damage/mutations and aging rate should exist, so that (i) the longer-lived individuals or species would have a lower rate of damage than the shorter-lived, and (ii) the interventions that modulate the level of DNA damage and repair capacity should also modulate the rate of aging and longevity and vice versa. The analysis of how the existing data meets the proposed criteria showed that many gaps should still be filled in order to reach a clear-cut conclusion. As a perspective, it seems that the main emphasis in future studies should be put on the role of DNA damage in stem cell aging. © 2012 Elsevier B.V.
Ouederni M.,Pediatric Hematology Immunology Unit |
Ouederni M.,Tunis el Manar University |
Sanal O.,Ankara University |
Ikinciogullari A.,Hacettepe University |
And 51 more authors.
Clinical Infectious Diseases | Year: 2014
Background. Interleukin 12Rβ1 (IL-12Rβ1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rβ1 deficiency.Results. Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin.Conclusions. Patients who are deficient in IL-12Rβ1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients. © The Author 2013.