Daniela Monti

Daniela Monti
University of Florence | UNIFI · Dipartimento di Scienze Biomediche, Sperimentali e Cliniche "Mario Serio"

PhD

About

304
Publications
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20,743
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Additional affiliations
January 2012 - present
January 2008 - present
January 2006 - present

Publications

Publications (304)
Article
Full-text available
Perilipin 2 (PLIN2) is a protein involved in lipid storage and metabolism in non-adipose tissues. Detectable levels of circulating PLIN2 (cPLIN2) have been reported to be associated with some types of cancer, but no systematic analysis of age-related modifications in cPLIN2 levels has ever been performed. We measured serum cPLIN2 in a group of old...
Article
Full-text available
Alzheimer's disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available D...
Preprint
Full-text available
Alzheimer’s disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in the brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly availab...
Article
Full-text available
Background and aim: A state of chronic, subclinical inflammation known as inflammaging is present in elderly people and represents a risk factor for all age-related diseases. Dietary supplementation with ad hoc fortified foods seems an appealing strategy to counteract inflammaging. The purpose of this study was to test the efficacy of elderly-tail...
Article
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Fibroblast Growth Factor 21 (FGF21), Growth Differentiation Factor 15 (GDF15), and Humanin (HN) are mitochondrial stress-related mitokines, whose role in health and disease is still debated. In this study, we confirmed that their plasma levels are positively correlated with age in healthy subjects. However, when looking at patients with type 2 diab...
Article
Context The aging phenotype is quite heterogeneous, being the result of the capability of each individual to successfully or unsuccessfully response to stressors. The reduction of homeostatic reserve characterizing aging is accompanied by a remodeling of the endocrine system. Frailty has been indicated as a promising way for capturing the physiolog...
Article
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Background The cline of human genetic diversity observable across Europe is recapitulated at a micro-geographic scale by variation within the Italian population. Besides resulting from extensive gene flow, this might be ascribable also to local adaptations to diverse ecological contexts evolved by people who anciently spread along the Italian Penin...
Article
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The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with i...
Article
Aging is characterized by dynamic changes at metabolic level that lead to modifications in the composition of the metabolome. Since the identification of biomarkers that can discriminate people of different age and health status has recently attracted a great interest, we wondered whether age-specific changes in the metabolome could be identified a...
Preprint
While many diseases of aging have been linked to the immunological system, immune metrics with which to identify the most at-risk individuals are lacking. Here, we studied the blood immunome of 1001 individuals age 8-96 and derived an inflammatory clock of aging (iAge), which tracked with multi-morbidity and immunosenescence. In centenarians, iAge...
Article
Thyroid plays a crucial and pervasive role in physiology (metabolism, thermogenesis and immunity, among others) and its aging and related changes in thyroid hormones production contribute to the common occurrence of thyroid diseases in elderly and to age-associated changes in other organs and systems. We address the complexity of thyroid aging foll...
Article
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Human longevity is a complex phenotype resulting from the combinations of context-dependent gene-environment interactions that require analysis as a dynamic process in a cohesive ecological and evolutionary framework. Genome-wide association (GWAS) and whole-genome sequencing (WGS) studies on centenarians pointed toward the inclusion of the apolipo...
Chapter
Inflammaging is a theory of aging based on the evidence that the evolutionary unpredicted persistent/increasing exposure to a variety of external and internal stressors occurring beyond the age of reproduction activates innate and adaptive immunity pathways involved in inflammatory response. Seventeen years after this theory was launched, it is now...
Article
Exposure to herbicides can induce long-term chronic adverse effects such as respiratory diseases, malignancies and neurodegenerative diseases. Oxadiazon, a pre-emergence or early post-emergence herbicide, despite its low acute toxicity, may induce liver cancer and may exert adverse effects on reproductive and on endocrine functions. Unlike other he...
Article
Full-text available
Thyroid hormones (FT3, FT4) and TSH were evaluated in a population of 672 well-characterized Italian subjects (age range: 52–113 years), including an unprecedented number of centenarians, semi-supercentenarians, as well as centenarian’s offspring and age-matched elderly (CENT, 105+, CENTOFF and CTRL, respectively). The results show that FT3 level a...
Article
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The study of the genetics of longevity has been mainly addressed by GWASs that considered subjects from different populations to reach higher statistical power. The "price to pay" is that population-specific evolutionary histories and trade-offs were neglected in the investigation of gene-environment interactions. We propose a new "diachronic" appr...
Article
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Age‐related changes in the brain reflect a dynamic interaction of genetic, epigenetic, phenotypic, and environmental factors that can be temporally restricted or more longitudinally present throughout the lifespan. Fundamental to these mechanisms is the capacity for physiological adaptation through modulation of diverse molecular and biochemical si...
Article
Mitochondrial stress elicits the production of stress response molecules indicated as mitokines, including FGF21, GDF15 and Humanin (HN). Many diseases are characterized by progressive mitochondrial dysfunction with alterations of mitokine secretion. It is still controversial whether healthy aging and extreme longevity are accompanied by altered pr...
Article
Full-text available
Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs) and geriatric syndromes (GSs), is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic...
Article
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The production of reactive oxygen species (ROS) may promote immunosenescence if not counterbalanced by the antioxidant systems. Cell membranes, proteins, and nucleic acids become the target of ROS and progressively lose their structure and functions. This process could lead to an impairment of the immune response. However, little is known about the...
Data
Table S1: list of the genes involved in response to the oxidative stress. Figure S1: percentage of methylation of the CpG sites throughout the GGT1 gene in the 3 ageing groups. Vertical bars represent the standard deviation of the mean of the methylation values for each CpG site in the 3 groups. Figure S2: percentage of methylation of the CpG sites...
Article
In order to better understand the pathogenesis of Parkinson's Disease (PD) it is important to consider possible contributory factors inherent to the aging process, as age-related changes in a number of physiological systems (perhaps incurred within particular environments) appear to influence the onset and progression of neurodegenerative disorders...
Article
Full-text available
Owing to its memory and plasticity, the immune system (IS) is capable of recording all the immunological experiences and stimuli it was exposed to. The combination of type, dose, intensity, and temporal sequence of antigenic stimuli that each individual is exposed to has been named “immunobiography.” This immunological history induces a lifelong co...
Article
Approximately one-quarter of the variation in lifespan in developed countries can be attributed to genetic factors. However, even large population based studies investigating genetic influence on human lifespan have been disappointing, identifying only a few genes accounting for genetic susceptibility to longevity. Some environmental and lifestyle...
Article
Human life expectancy and the number of the oldest old are rapidly increasing worldwide. Advanced age is the main risk factor for dementia, representing one of the major causes of disability/dependency among older people with a strong impact on their families/caregivers. Centenarians have reached the extreme limits of human life escaping or delayin...
Article
In this review we address the genetic continuum between aging and age-related diseases, with particular attention to the ecological perspective. We describe the connections between genes that promote longevity and genes associated to age-related diseases considering trade-off mechanisms in which the same genetic variants could have different effect...
Article
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Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene–environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the mos...
Article
The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach...
Article
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Within the scenario of an increasing life expectancy worldwide it is mandatory to identify determinants of healthy aging. Centenarian offspring (CO) is one of the most informative model to identify trajectories of healthy aging and their determinants (genetic and environmental), being representative of elderly in their 70th whose lifestyle can be s...
Article
Full-text available
The pro- or anti-inflammatory activities of immunoglobulins G (IgGs) are controlled by the structure of the glycan N-linked to Asn297 of their heavy chain. The age-associated low grade inflammation (inflammaging) is associated with increased plasmatic levels of agalactosylated IgGs terminating with N-acetylglucosamine (IgG-G0) whose biogenesis has...
Article
Full-text available
Given the dramatic increase in ageing populations, it is of great importance to understand the genetic and molecular determinants of healthy ageing and longevity. Semi-supercentenarians (subjects who reached an age of 105-109 years) arguably represent the gold standard of successful human ageing because they managed to avoid or postpone the onset o...
Article
Full-text available
We developed a new statistical framework to find genetic variants associated with extreme longevity. The method, informed GWAS (iGWAS), takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity. To gain support for our approach, we first show there is an overlap between l...
Data
GWAS that do not show genetic overlap with exceptional longevity. As in Fig 1, the blue lines show the P values for longevity of the top 100, 250, and 500 SNPs from independent genetic loci, and the red lines show the background distribution of longevity P values. (*) P < 0.05, (**) P < 0.005. (PDF)
Data
Nine diseases show genetic overlap with longevity. For each of the 9 disease datasets showing a genetic overlap with longevity, we provide hypergeometric P values and fold enrichment, and identities of disease SNPs that are nominally associated with longevity (from the top 100). (XLSX)
Data
Regional plots for longevity-associated SNPs identified by iGWAS (NECS). Green boxes indicate genes harboring missense SNPs in LD with candidate longevity SNPs, and magenta boxes genes for which a candidate longevity SNP is an eQTL. (PDF)
Data
98 SNPs representing 8 unique genetic loci are significant in a longevity GWAS weighted by disease. (XLSX)
Data
eQTL results for all longevity SNPs, at a false discovery rate < 5%. (XLSX)
Data
Imputation results for candidate longevity SNPs in NECS. (XLSX)
Data
Deriving optimal P value weights. Methods used to derive the P value weighting scheme used in iGWAS. (DOCX)
Data
Regional plots for longevity-associated SNPs identified by iGWAS (90PLUS). Green boxes indicate genes harboring missense SNPs in LD with candidate longevity SNPs, and magenta boxes genes for which a candidate longevity SNP is an eQTL. (PDF)
Data
Proxy SNPs used for replication, when data for lead SNP was missing. The best proxy SNP such that R2 > 0.8 and D’ = 1 was identified using data from two reference populations, 1000 Genomes and HapMap release 22 (Broad Institute SNAP tool[64]). (XLSX)
Data
GWAS that show genetic overlap with exceptional longevity. As in Fig 1, the blue lines show the P values for longevity of the top 100, 250, and 500 SNPs from independent genetic loci, and the red lines show the background distribution of longevity P values. (*) P < 0.05, (**) P < 0.005. (PDF)
Article
Full-text available
At present, women show a higher life expectancy than men and this gender diff erence is becoming a worldwide phenomenon indicating the central demographic role of gender in ageing and longevity. A combination of genetic, environmental, historical, anthropo-logical, socioeconomic and cultural aspects as well as the geographical origin is at the basi...
Article
Full-text available
Leukocyte telomere length (LTL) has been observed to be hereditable and correlated with longevity. However, contrasting results have been reported in different populations on the value of LTL heritability and on how biology of telomeres influences longevity. We investigated whether the variability of genes correlated to telomere maintenance is asso...
Article
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(i) investigate the transmission of low level heteroplasmies in the elderly; (ii) explore the association of heteroplasmy with age and longevity and (iii) investigate heteroplasmy patterns in these three groups. We sequenced a 853 bp mtDNA fragment in 88 individuals to an average coverage of 49334-fold, using quality control filtering and triplicat...
Article
Mitochondrial components, including mitochondrial DNA (mtDNA), when released extracellularly, can act as "damage-associated molecular pattern" (DAMP) agents and cause inflammation. As many elderly people are characterized by a low-grade, chronic inflammatory status defined "inflamm-aging", we evaluated if circulating mtDNA can contribute to this ph...
Article
Full-text available
Usually the genetics of human longevity is restricted to the nuclear genome (nDNA). However it is well known that the nDNA interacts with a physically and functionally separated genome, the mitochondrial DNA (mtDNA) that, even if limited in length and number of genes encoded, plays a major role in the ageing process. The complex interplay between n...
Article
Like almost all vertebrates, humans have developed a complex immune system, which evolved in an environment that prompted the development of sophisticated strategies of antigen recognition due to the necessity to discriminate relatively few pathogens among huge amounts of commensal microorganisms, and tolerate self antigens as well as food antigens...
Article
Centenarians are rare and exceptional individuals characterized by a peculiar phenotype. They are the best example of healthy ageing in humans as most of them have escaped or substantially delayed the onset of major age-related diseases. Within this scenario, the purpose of the present work was to understand if immune status is associated with surv...
Article
Full-text available
As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals....
Article
Full-text available
Alterations in the circulating CD8+ T cell pool, with a loss of naïve and accumulation of effector/effector memory cells, are pronounced in older adults. However, homeostatic forces that dictate such changes remain incompletely understood. This observational cross-sectional study explored the basis for variability of CD8+ T cell number and composit...