1,721,153 research outputs found
Response by Giuliani et al to Letter Regarding Article, "genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework"
Full text linkComment on Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework. [Circ Res. 2018]
Letter by Morris Regarding Article, "Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework". [Circ Res. 2019
Genetics of human longevity within an eco-evolutionary nature-nurture framework
Full text linkHuman longevity is a complex trait, and to disentangle its basis has a great theoretical and practical consequences for biomedicine. The genetics of human longevity is still poorly understood despite several investigations that used different strategies and protocols. Here, we argue that such rather disappointing harvest is largely because of the extraordinary complexity of the longevity phenotype in humans. The capability to reach the extreme decades of human lifespan seems to be the result of an intriguing mixture of gene-environment interactions. Accordingly, the genetics of human longevity is here described as a highly context-dependent phenomenon, within a new integrated, ecological, and evolutionary perspective, and is presented as a dynamic process, both historically and individually. The available literature has been scrutinized within this perspective, paying particular attention to factors (sex, individual biography, family, population ancestry, social structure, economic status, and education, among others) that have been relatively neglected. The strength and limitations of the most powerful and used tools, such as genome-wide association study and whole-genome sequencing, have been discussed, focusing on prominently emerged genes and regions, such as apolipoprotein E, Forkhead box O3, interleukin 6, insulin-like growth factor-1, chromosome 9p21, 5q33.3, and somatic mutations among others. The major results of this approach suggest that (1) the genetics of longevity is highly population specific; (2) small-effect alleles, pleiotropy, and the complex allele timing likely play a major role; (3) genetic risk factors are age specific and need to be integrated in the light of the geroscience perspective; (4) a close relationship between genetics of longevity and genetics of age-related diseases (especially cardiovascular diseases) do exist. Finally, the urgent need of a global approach to the largely unexplored interactions between the 3 genetics of human body, that is, nuclear, mitochondrial, and microbiomes, is stressed. We surmise that the comprehensive approach here presented will help in increasing the above-mentioned harvest
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
Ecological Sensing through Taste and Chemosensation Mediates Inflammation: A Biological Anthropological Approach
Full text linkEcological sensing and inflammation have evolved to ensure optima between organism survival and reproductive success in different and changing environments. At the molecular level, ecological sensing consists of many types of receptors located in different tissues that orchestrate integrated responses (immune, neuroendocrine systems) to external and internal stimuli. This review describes emerging data on taste and chemosensory receptors, proposing them as broad ecological sensors and providing evidence that taste perception is shaped not only according to sense epitopes from nutrients but also in response to highly diverse external and internal stimuli. We apply a biological anthropological approach to examine how ecological sensing has been shaped by these stimuli through human evolution for complex interkingdom communication between a host and pathological and symbiotic bacteria, focusing on population-specific genetic diversity. We then focus on how these sensory receptors play a major role in inflammatory processes that form the basis of many modern common metabolic diseases such as obesity, type 2 diabetes, and aging. The impacts of human niche construction and cultural evolution in shaping environments are described with emphasis on consequent biological responsiveness
DNA METHYLATION CORRELATION STRUCTURE OF CHROMOSOME 21 IN DOWN SYNDROME
No full textDNA methylation studies usually focus on the groups of CpG sites. Neighbouring CpG sites are analyzed together due to their group behaviour. However, this approach ignores the possible interaction between more distant CpG sites. In this work, we investigate the complete methylation correlation structure of chromosome 21. Two data sets were used for the correlation analysis, smaller data set with methylation measurements from Down syndrome patients and their family members and larger data set with healthy subjects. This allowed us to examine the general properties of the methylation correlation structure as well as its modifications in presence of an extra copy of the chromosome. We observed that the CpG sites work in small highly correlated groups. While some groups coincided with CpG islands, other groups contained CpG sites scattered across the whole chromosome. Groups of highly correlated CpG sites remained preserved in the case of Down syndrome. Moreover, the methylome of a Down syndrome patient had newly formed correlations between CpG sites suggesting that the methylation correlation structure in Down syndrome is stronger than in case of an unaffected individual
Down syndrome, accelerated aging and immunosenescence
Full text linkDown syndrome is the most common chromosomal disorder, associated with moderate to severe intellectual disability. While life expectancy of Down syndrome population has greatly increased over the last decades, mortality rates are still high and subjects are facing prematurely a phenomenon of atypical and accelerated aging. The presence of an immune impairment in Down syndrome subjects is suggested for a long time by the existence of an increased incidence of infections, the incomplete efficacy of vaccinations, and a high prevalence of autoimmunity. Immunologic abnormalities have been described since many years in this population, both from a numerical and a functional points of view, and these abnormalities can mirror the ones observed during normal aging. In this review, we summarize our knowledge on immunologic disturbances commonly observed in subjects with Down syndrome, and in innate and adaptive immunity, as well as regarding chronic inflammation. We then discuss the role of accelerated aging in these observed abnormalities and finally review the potential age-associated molecular and cellular mechanisms involved
The role of extracellular DNA in COVID-19: Clues from inflamm-aging
No full textEpidemiological data convey severe prognosis and high mortality rate for COVID-19 in elderly men affected by age-related diseases. These subjects develop local and systemic hyper-inflammation, which are associated with thrombotic complications and multi-organ failure. Therefore, understanding SARS-CoV-2 induced hyper-inflammation in elderly men is a pressing need. Here we focus on the role of extracellular DNA, mainly mitochondrial DNA (mtDNA) and telomeric DNA (telDNA) in the modulation of systemic inflammation in these subjects. In particular, extracellular mtDNA is regarded as a powerful trigger of the inflammatory response. On the contrary, extracellular telDNA pool is estimated to be capable of inhibiting a variety of inflammatory pathways. In turn, we underpin that telDNA reservoir is progressively depleted during aging, and that it is scarcer in men than in women. We propose that an increase in extracellular mtDNA, concomitant with the reduction of the anti-inflammatory telDNA reservoir may explain hyper-inflammation in elderly male affected by COVID-19. This scenario is reminiscent of inflamm-aging, the portmanteau word that depicts how aging and aging related diseases are intimately linked to inflammation
Inflammaging: a new immune–metabolic viewpoint for age-related diseases
Full text linkAgeing and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. During ageing, chronic, sterile, low-grade inflammation — called inflammaging — develops, which contributes to the pathogenesis of age-related diseases. From an evolutionary perspective, a variety of stimuli sustain inflammaging, including pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows them to recognize many signals and to activate the innate immune responses, sense these stimuli. In this situation, metaflammation (the metabolic inflammation accompanying metabolic diseases) is thought to be the form of chronic inflammation that is driven by nutrient excess or overnutrition; metaflammation is characterized by the same mechanisms underpinning inflammaging. The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products, contribute to circadian rhythms and crosstalk with other organs and systems. We argue that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing. Finally, we propose the use of new biomarkers (DNA methylation, glycomics, metabolomics and lipidomics) that are capable of assessing biological versus chronological age in metabolic diseases
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
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