Elimination of damaged mitochondria during UVB-induced senescence is orchestrated by NIX-dependent mitophagy.

Skin aging is the result of two types of aging, "intrinsic aging" an inevitable consequence of physiologic and genetically determined changes and "extrinsic aging," which is dependent on external factors such as exposure to sunlight, smoking, and dietary habits. UVB causes skin injury through the generation of free radicals and other oxidative byproducts, also contributing to DNA damage. Appearance and accumulation of senescent cells in the skin are considered one of the hallmarks of aging in this tissue.

miR-142 favors naïve B cell residence in peripheral lymph nodes.

B lymphocyte development proceeds through a well-ordered sequence of steps, leading to the formation of a sizeable mature B population recognizing a diversity of antigens. These latter cells are ultimately responsible for the production of antibodies upon immune challenges. The detection of threats to the organism is facilitated by the ability of naïve follicular B cells, the main subset of mature B cells in mice, to circulate between lymphoid tissues in search of their cognate antigens.

Human bone marrow adipocytes display distinct immune regulatory properties.

Background: The bone marrow (BM) is a major reservoir of resting memory T cells and long-lived plasma cells, capable of providing protection against recurrent infections. Whether the age-related accumulation of adipose tissue in the BM affects the functionality and maintenance of memory cells is not well understood.

Methods: For the first time, we compare human femur marrow adipose tissue (fMAT) and subcutaneous white adipose tissue of the thigh (tsWAT) obtained from the same donors.

Fcμ receptor as a Costimulatory Molecule for T Cells.

Fc receptor for IgM (FcμR)-deficient mice display dysregulated function of neutrophils, dendritic cells, and B cells. The relevance of FcμR to human T cells is still unknown. We show that FcμR is mostly stored inside the cell and that surface expression is tightly regulated.

Increased IL-15 Production and Accumulation of Highly Differentiated CD8 Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus.

Cytomegalovirus (CMV) has been described as a contributor to immunosenescence, thus exacerbating age-related diseases. In persons with latent CMV infection, the CD8 T cell compartment is irreversibly changed, leading to the accumulation of highly differentiated virus-specific CD8 T cells in the peripheral blood. The bone marrow (BM) has been shown to play a major role in the long-term survival of antigen-experienced T cells.

CD146 (MCAM) in human cs-DLK1/cs-CD34 adipose stromal/progenitor cells.

To precisely characterize CD146 in adipose stromal/progenitor cells (ASCs) we sorted the stromal vascular faction (SVF) of human abdominal subcutaneous white adipose tissue (sWAT) according to cell surface (cs) expression of CD146, DLK1 and CD34. This test identified three main SVF cell populations: ~50% cs-DLK1/cs-CD34/cs-CD146 ASCs, ~7.5% cs-DLK1/cs-CD34/cs-CD146 and ~7.

UVB-Induced Senescence of Human Dermal Fibroblasts Involves Impairment of Proteasome and Enhanced Autophagic Activity.

In the current study, we have extended previous findings aiming at a better understanding of molecular mechanisms underlying UVB-induced senescence of diploid human dermal fibroblasts (HDFs), an experimental model to study the process of photoaging in the skin. We provide evidence that the inhibition of proteasomal degradation of damaged proteins and the activation of autophagosome formation are early events in UVB-induced senescence of HDFs, dependent on UVB-induced accumulation of reactive oxygen species. Our data suggest that autophagy is required for the establishment of the senescent phenotype in UVB-treated HDFs and that inhibition of autophagy is sufficient to change the cell fate from senescence to cell death by apoptosis.

Analysis of human papillomavirus E7 protein status in C-33A cervical cancer cells.

High-risk human papillomaviruses (HPV) are the main etiologic factor for the development of cervical cancer. Infections by these viruses have been detected in virtually all cervical cancers. C-33A is one of the rare cervical cancer derived cell lines considered as HPV-negative.

The impact of aging on memory T cell phenotype and function in the human bone marrow.

Recently, the BM has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4⁺ and CD8⁺ T cells in the BM is maintained during aging.

Human bone marrow hosts polyfunctional memory CD4+ and CD8+ T cells with close contact to IL-15-producing cells.

Recently, a key role in memory T cell homing and survival has been attributed to the bone marrow (BM) in mice. In the human BM, the repertoire, function, and survival niches of CD4(+) and CD8(+) T cells have not yet been elucidated. In this study, we demonstrate that CD4(+) and CD8(+) effector memory T cells accumulate in the human BM and are in a heightened activation state as revealed by CD69 expression.

Immunodominant peptides from conserved influenza proteins--a tool for more efficient vaccination in the elderly?

Influenza-specific CD8+ T cells are important for the clearance of infection especially in high risk groups such as elderly persons. Activation of these cells by immunization might therefore be a useful tool for a better protection of this specific age group. We therefore analyzed the frequency, phenotype and function of CD8+ T cells with specificity to the influenza M1(58-66) peptide in young, middle-aged and elderly persons ex vivo and after in vitro stimulation.

Insufficient protection for healthy elderly adults by tetanus and TBE vaccines.

Little information is available on post-vaccination antibody concentrations and the duration of protection in persons of more than 20 years of age. We, therefore, measured antibodies specific for tetanus (TT) or tick-borne encephalitis (TBE) virus in 734 adults (age 18-93 years, 382 females and 352 males) and evaluated these data in connection with the time point of the last vaccination against tetanus or TBE and age. This analysis revealed that the time of the last vaccination as well as age had highly significant effects on tetanus and TBE titers (p < 0.

Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons.

In spite of the present belief that latent cytomegalovirus (CMV) infection drives CD8+ T-cell differentiation and induces premature immune senescence, no systematic studies have so far been performed to compare phenotypical and functional changes in the CD8+ T-cell repertoire in CMV-infected and noninfected persons of different age groups. In the present study, number, cytokine production, and growth potential of naive (CD45RA+ CD28+), memory (CD45RA- CD28+), and effector (CD45RA+ CD28- or CD45RA- CD28-) CD8+ T cells were analyzed in young, middle-aged, and elderly clinically healthy persons with a positive or negative CMV antibody serology. Numbers and functional properties of CMVpp65(495-503)-specific CD8+ T cells were also studied.

Age-related loss of naïve T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes.

In this study we analysed the effects of age on T and B lymphocytes in human lymph nodes by comparing lymphocyte subsets in paraffin sections from lymph node tissue taken from healthy young and elderly people. We demonstrate that the relative number of CD8(+) T cells decreases with age but that the relative number of CD4(+) T cells does not. There is also a very pronounced age-dependent loss of CD45RA(+) naive T cells.

Association of increased neopterin production with decreased humoral immunity in the elderly.

Tetanus toxoid (TT) antibodies of 447 adult persons aged 27-69 years were investigated and analyzed in relationship with the time span since the last vaccination against tetanus as well as the serum concentration of neopterin. Neopterin is a pteridine, which is produced by monocytes/macrophages upon stimulation with the type 1 T cell-derived cytokine interferon-gamma. There was an inverse correlation between serum neopterin and TT antibody concentrations (Spearman's rank correlation coefficient: r(s)=-0.

IL-4-producing CD8+ T cells with a CD62L++(bright) phenotype accumulate in a subgroup of older adults and are associated with the maintenance of intact humoral immunity in old age.

An increased production of proinflammatory cytokines occurs in a high percentage of elderly persons and is associated with an impaired humoral immune response. However, high IL-4 production has also been observed in old age. We now demonstrate an IL-4-producing subpopulation of CD8+ T cells in a subgroup of healthy older adults.

[Vaccine protection in the elderly: are Austrian seniors adequately protected by vaccinations?].

Objective: The aim of the study was to evaluate, if elderly persons are sufficiently protected against infectious diseases by vaccination.

Probands And Methods: 300 elderly (> 60 years) and 300 young (< 35 years) persons from five Austrian cities were recruited according to the criteria of a field study. Antibody concentrations against tetanus, diphtheria, tickborne encephalitis and influenza were assessed by ELISA or by haemagglutination inhibition test.