0000000000336389
AUTHOR
Annibale Alessandro Puca
Genetics of exceptional longevity: possible role of GM allotypes
NOT REQUESTED FOR COMMENTARIES
A G613A missense in the Hutchinson's progeria lamin A/C gene causes a lone, autosomal dominant atrioventricular block.
Background LMNA/C mutations have been linked to the premature aging syndrome Hutchinson’s progeria, dilated cardiomyopathy 1A, skeletal myopathies (such as the autosomal dominant variant of Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy), Charcot-Marie-Tooth disorder type 2B1, mandibuloacral dysplasia, autosomal dominant partial lipodystrophy, and axonal neuropathy. Atrioventricular block (AVB) can be associated with several cardiac disorders and it can also be a highly heritable, primitive disease. One of the most common pathologies associated with AVB is dilated cardiomyopathy (DCM), which is characterized by cardiac dilatation and reduced systolic function. In this …
“Positive biology”: the centenarian lesson
Abstract The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years, because of the increased number of individuals not autonomous and affected by invalidating pathologies. Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing select…
Taste receptors, innate immunity and longevity: the case of TAS2R16 gene
Abstract Background Innate immunity utilizes components of sensory signal transduction such as bitter and sweet taste receptors. In fact, empirical evidence has shown bitter and sweet taste receptors to be an integral component of antimicrobial immune response in upper respiratory tract infections. Since an efficient immune response plays a key role in the attainment of longevity, it is not surprising that the rs978739 polymorphism of the bitter taste receptor TAS2R16 gene has been shown to be associated with longevity in a population of 941 individuals ranging in age from 20 to 106 years from Calabria (Italy). There are many possible candidate genes for human longevity, however of the many…
The application of genetics approaches to the study of exceptional longevity in humans: Potential and limitations
Abstract The average life-span of the population of industrialized countries has improved enormously over the last decades. Despite evidence pointing to the role of food intake in modulating life-span, exceptional longevity is still considered primarily an inheritable trait, as pointed out by the description of families with centenarian clusters and by the elevated relative probability of siblings of centenarians to become centenarians themselves. However, rather than being two separate concepts, the genetic origin of exceptional longevity and the more recently observed environment-driven increase in the average age of the population could possibly be explained by the same genetic variants …
Exome sequencing of a family with lone, autosomal dominant atrial flutter identifies a rare variation in ABCB4 significantly enriched in cases
Background Lone atrial flutter (AFL) and atrial fibrillation (AF) are common and sometimes consequential cardiac conduction disorders with a strong heritability, as underlined by recent genome-wide association studies that identified genetic modifiers. Follow-up family-based genetic analysis also identified Mendelian transmission of disease alleles. Three affected members were exome-sequenced for the identification of potential causative mutations, which were subsequently validated by direct sequencing in the other 3 affected members. Taqman assay was then used to confirm the role of any mutation in an independent population of sporadic lone AFL/AF cases. Results The family cluster analysis…
Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases
Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic stra…
Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases.
Resveratrol-a natural polyphenolic compound-was first discovered in the 1940s. Although initially used for cancer therapy, it has shown beneficial effects against most cardiovascular and cerebrovascular diseases. A large part of these effects are related to its antioxidant properties. Here we review: (a) the sources, the metabolism, and the bioavailability of resveratrol; (b) the ability of resveratrol to modulate redox signalling and to interact with multiple molecular targets of diverse intracellular pathways; (c) its protective effects against oxidative damage in cardio-cerebro-vascular districts and metabolic disorders such as diabetes; and (d) the evidence for its efficacy and toxicity…
Special Issue "Centenarians-A Model to Study the Molecular Basis of Lifespan and Healthspan".
People are living longer, not, as was previously the case, due to reduced child mortality, but because we are postponing the ill-health of old age [...]
Taste receptor polymorphisms and longevity: a systematic review and meta-analysis
AbstractBitter taste receptors (TAS2R) are involved in a variety of non-tasting physiological processes, including immune-inflammatory ones. Therefore, their genetic variations might influence various traits. In particular, in different populations of South Italy (Calabria, Cilento, and Sardinia), polymorphisms of TAS2R16 and TAS238 have been analysed in association with longevity with inconsistent results. A meta-analytic approach to quantitatively synthesize the possible effect of the previous variants and, possibly, to reconcile the inconsistencies has been used in the present paper. TAS2R38 variants in the Cilento population were also analysed for their possible association with longevi…
Association of immunoglobulin GM allotypes with longevity in long-living individuals from Southern Italy
Abstract Background The aim of this study was to analyse the role of GM allotypes, i.e. the hereditary antigenic determinants expressed on immunoglobulin polypeptide chains, in the attainment of longevity. The role played by immunoglobulin allotypes in the control of immune responses is well known as well as the role of an efficient immune response in longevity achievement. So, it is conceivable that particular GM allotypes may contribute to the generation of an efficient immune response that supports successful ageing, hence longevity. Methods In order to show if GM allotypes play a role in the achievement of longevity, we typed the DNA of 95 Long-living individuals (LLIs) and 96 young con…
Genetic signatures of centenarians: Implications for achieving successful aging
The extraordinary rise in the old population in the Western world underscores the importance of studies on aging and longevity to decrease the medical, economic and social problems associated with the increased number of non-autonomous individuals affected by invalidating pathologies. Centenarians have reached the extreme limits of the human life span. They are the best example of extreme longevity, representing selected individuals in which the appearance of major age-related diseases has been consistently delayed or avoided. There is growing evidence that the genetic component of longevity becomes higher with survival at the age of over 90 years. For centenaries, it reaches up to 33% for…
Serum BPIFB4 levels classify health status in long-living individuals
Background People that reach extreme ages (Long-Living Individuals, LLIs) are object of intense investigation for increase/decrease of genetic variant frequencies, genetic methylation levels, protein abundance in serum and tissues. The aim of these studies is the discovery of the mechanisms behind LLIs extreme longevity and the identification of markers of well-being. We have recently associated a BPIFB4 haplotype (LAV) with exceptional longevity under a homozygous genetic model, and identified that CD34+ of LLIs subjects express higher BPIFB4 transcript as compared to CD34+ of control population. It would be of interest to correlate serum BPIFB4 protein levels with exceptional longevity an…
Immunomodulatory activity of Humulus lupulus bitter acids fraction: Enhancement of natural killer cells function by NKp44 activating receptor stimulation
Abstract Humulus lupulus (Hop) contains numerous metabolites with anticancer potential. Despite this, their immunomodulatory activity, and in particular of bitter acids, is unknown. In this study, we demonstrated that a Hop pellet extract fraction containing bitter acids possesses immunomodulatory activity by enhancing Natural Killer (NK) cells function. After fractionation by semi-preparative Liquid Chromatography, three different fractions were obtained. The phytocomplex and the fractions were tested to verify the ability to modulate the NK compartment. Cytofluorimetric analysis revealed that a fraction containing bitter acids was able to up-regulate of NKG2D and NKp44 activating receptor…
Centenarians as a model to discover genetic and epigenetic signatures of healthy ageing.
Abstract Centenarians are a model of successful ageing. The data favours the theory that, in order to live to 100, it is mandatory to inherit the right genetic variants from parents or acquire epigenetic variants through the environment. Therefore, the study of epigenetic signatures of healthy ageing is becoming an important aspect to identify the role of chromatin modification in ageing and understand how manage this fine-tuning system. So, according to the concept of developmental plasticity, establishment of a longevity phenotype requires a combination of stochastic and non-stochastic events that modulate the genetic substrate and leads to a different outcome. It can be concluded that ce…