1,721,226 research outputs found
The Contextualized Genetics of Human Longevity: JACC Focus Seminar
No full textThe genetics of human longevity has long been studied, and in this regard, centenarians represent a very informative model. Centenarians are characterized by 2 main features: 1) the capability to avoid or postpone the major age-related diseases; and 2) a high level of heterogeneity of their phenotype. The first suggests that longevity and resistance to diseases are mediated by shared mechanisms, the latter that many strategies can be used to become long lived, likely as a result of variable genome-environment interactions. The authors suggest that the complexity of genome-environment interactions must be considered within an evolutionary and ecological perspective and that the concept of “risk allele” is highly context dependent, changing with age, time, and geography. Genes involved in both longevity and cardiovascular diseases, taken as a paradigmatic example of age-related diseases, as well as other emerging topics in genetics of longevity, such as micro–ribonucleic acid (miRNA) genetics, polygenic risk scores, environmental pollutants, and somatic mutations are discussed
The Dual Role of the Pervasive "Fattish" Tissue Remodeling With Age
Full text linkHuman aging is characterized by dramatic changes in body mass composition that include a general increase of the total fat mass. Within the fat mass, a change in the proportions of adipose tissues also occurs with aging, affecting body metabolism, and playing a central role in many chronic diseases, including insulin resistance, obesity, cardiovascular diseases, and type II diabetes. In mammals, fat accumulates as white (WAT) and brown (BAT) adipose tissue, which differ both in morphology and function. While WAT is involved in lipid storage and immuno-endocrine responses, BAT is aimed at generating heat. With advancing age BAT declines, while WAT increases reaching the maximum peak by early old age and changes its distribution toward a higher proportion of visceral WAT. However, lipids tend to accumulate also within lipid droplets (LDs) in non-adipose tissues, including muscle, liver, and heart. The excess of such ectopic lipid deposition and the alteration of LD homeostasis contribute to the pathogenesis of the above-mentioned age-related diseases. It is not clear why age-associated tissue remodeling seems to lean toward lipid deposition as a "default program." However, it can be noted that such remodeling is not inevitably detrimental. In fact, such a programmed redistribution of fat throughout life could be considered physiological and even protective, in particular at extreme old age. In this regard, it has to be considered that an excessive decrease of subcutaneous peripheral fat is associated with a pro-inflammatory status, and a decrease of LD is associated with lipotoxicity leading to an increased risk of insulin resistance, type II diabetes and cardiovascular diseases. At variance, a balanced rate of fat content and distribution has beneficial effects for health and metabolic homeostasis, positively affecting longevity. In this review, we will summarize the present knowledge on the mechanisms of the age-related changes in lipid distribution and we will discuss how fat mass negatively or positively impacts on human health and longevity
Use of flow cytometry as a tool to study mitochondrial membrane potential in isolated, living hepatocytes
No full textThe present paper describes the possibility of determination of mitochondrial membrane potential (Delta omega) in isolated hepatocytes making use of a Delta psi-sensitive dye, i.e., the lipophilic cationic probe 5,5'6,6'-tetrachloro-1,1'3,3 '-tetraethylbenzimidazolcarbocyanine iodide (JC-1) and of cytofluorimetry. The validity of the method was proved by treating hepatocytes with FCCP (decrease of Delta psi) and subsequent addition of 6-ketocholestanol (increase of Delta psi). The results indicate that the proposed method may be used in laboratory practice
Mitochondria, immunosenescence and inflammaging: a role for mitokines?
Full text linkA global reshaping of the immune responses occurs with ageing, indicated as immunosenescence, where mitochondria and mitochondrial metabolism play an important role. However, much less is known about the role of mitochondrial stress response in this reshaping and in particular of the molecules induced by such response, collectively indicated as mitokines. In this review, we summarize the current knowledge on the role of mitokines in modulating immune response and inflammation focusing on GDF15, FGF21 and humanin and their possible involvement in the chronic age-related low-grade inflammation dubbed inflammaging. Although many aspects of their biology are still controversial, available data suggest that these mitokines have an anti-inflammatory role and increase with age. Therefore, we hypothesize that they can be considered part of an adaptive and integrated immune-metabolic mechanism activated by mitochondrial dysfunction that acts within the framework of a larger anti-inflammatory network aimed at controlling both acute inflammation and inflammaging
CYTOTOXICITY AND CELL-DEATH - STUDIES ON MOLLUSCAN CELLS AND EVOLUTIONARY CONSIDERATIONS
No full textIn a previous study we demonstrated the presence of NK-like activity in the mollusc Planorbarius corneus. This activity ran be ascribed to round hemocytes that have a morphology similar to that of vertebrate lymphocytes. We show here that this NK-like cytotoxicity is evident in serum-free culture medium. Moreover, the type of death induced by molluscan effector cells on their targets is probably similar to that induced by vertebrate effector cells, i.e. apoptosis or programmed cell death, as assessed by the protective effect exerted by 3-aminobenzamide when both types of effector cells were used
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Inflammaging Targets
No full textInflammaging refers to the chronic, low-grade inflammation that develops with age and may favor the onset of age-related diseases (ARDs) and geriatric syndromes (GSs). Many molecular mechanisms are involved in causing inflammaging, from innate immunity activation to increased availability of DAMPs and to mitochondria-ER stress. Inflammaging is emerging as pervasive phenomenon acting in a multi-layer fashion, whose targets range from molecular, cellular, tissue/organ and system levels. In this article we will briefly summarize and discuss the main targets for which experimental evidence is available. Importantly, inflammaging is also found in long-lived persons such as centenarians and low levels of inflammation are important for normal development and function of many cell types and tissues. This apparent paradox can be explained by the fact that inflammaging is likely an adaptive response to stress- and age-related processes and includes both inflammatory and antiinflammatory mediators that are inextricably interconnected. The net result depends on the balance between these mediators, on the timing of their production and on the cell type affected
- …
