The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Thomas T Perls - One of the best experts on this subject based on the ideXlab platform.
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a serum protein signature of apoe genotypes in Centenarians
Innovation in Aging, 2019Co-Authors: Stefano Monti, Paola Sebastiani, Anastasia Gurinovich, Toshiko Tanaka, Lori L Jennings, David J Glass, Thomas T PerlsAbstract:The discovery of treatments to prevent or delay Alzheimer’s disease is a priority. The gene APOE is associated with cognitive change and late onset Alzheimer’s disease, and epidemiological studies have shown that the e_2 allele of APOE has a neuroprotective effect, and it is associated with increased longevity. We correlated APOE genotype data of 222 New England Centenarian Study participants, including 79 Centenarians, 84 centenarian offspring and 55 carriers of APOE e_2, with aptamer-based serum proteomics (SomaLogic technology) of 4783 human proteins corresponding to 4137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes, and replicated the signature in 3 independent studies. We show that the protein signature tracks with gene expression profiles in brains of late onset Alzheimer’s disease vs. healthy controls. Finally, we show that seven of these proteins correlate with cognitive function changes. Therefore, targeting APOE e_2 molecularly may preserve cognitive function.
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personality traits of Centenarians offspring
Journal of the American Geriatrics Society, 2009Co-Authors: Jane L Givens, Paola Sebastiani, Dellara F Terry, Margery Silver, Maureen Frederick, Leanne Silverman, Stacy Anderson, Joanna Senville, Paul T Costa, Thomas T PerlsAbstract:Research on siblings and offspring of Centenarians has documented that exceptional longevity runs strongly in families.1–4 Studies of the offspring of Centenarians have shown that their mortality is lower that that of other members of their birth cohort5 and that they have lower prevalence1,6 and delayed onset of cardiovascular disease, hypertension, and diabetes mellitus.7 Thus, they are regarded as a model of healthy aging. Because personality traits have been shown to have substantial heritable components, 8 it was hypothesized that certain personality features may be important to the healthy aging observed in the offspring of Centenarians. Several studies have assessed the effect of personality traits on survival using the Five-Factor Model (FFM) of Personality. Studies have used the Revised NEO Personality Inventory, a 240-item measure of the five broad factors and the 30 narrower facet scales or the NEO Five-Factor Inventory (NEO-FFI), a 60-item self-report questionnaire that measures only the five personality factors: neuroticism (emotional reactivity and distress), extraversion (tendency to be outgoing, active), openness (flexibility and openness to new ideas), agreeableness (cooperation and empathy), and conscientiousness (social responsibility and self-discipline).9 Findings from longitudinal studies have, to some extent, been consistent, indicating that high conscientiousness, low neuroticism, and perhaps high extraversion are predictive of lower mortality and longevity in aging populations.10–13 Prior research suggests that offspring of Centenarians are a model of healthy aging and that certain personality traits are associated with mortality and longevity. Thus, this study aimed to test the hypothesis that above-average levels of health-promoting traits (e.g., conscientiousness and extraversion) and below-average levels of health-damaging traits (e.g., neuroticism) characterize offspring of Centenarians. Using the NEO-FFI from the FFM, this study set out to measure the personality characteristics of offspring of Centenarians and to compare NEO-FFI scores of Centenarians’ offspring with normative scores.
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association of longer telomeres with better health in Centenarians
Journals of Gerontology Series A-biological Sciences and Medical Sciences, 2008Co-Authors: Dellara F Terry, Stacy L Andersen, Thomas T Perls, Vikki G Nolan, Richard M CawthonAbstract:Prior animal model studies have demonstrated an association between telomere length and longevity. Our study examines telomere length in Centenarians in good health versus poor health. Using DNA from blood lymphocytes, telomere length was measured by quantitative polymerase chain reaction in 38 sex- and age-matched Centenarians (ages 97-108). "Healthy" Centenarians (n = 19) with physical function in the independent range and the absence of hypertension, congestive heart failure, myocardial infarction, peripheral vascular disease, dementia, cancer, stroke, chronic obstructive pulmonary disease, and diabetes were compared to Centenarians with physical function limitations and > or =2 of the above conditions (n = 19). Healthy Centenarians had significantly longer telomeres than did unhealthy Centenarians (p =.0475). Our study demonstrated that investigations of the association between telomere length and exceptional longevity must take into account the health status of the individuals. This raises the possibility that perhaps it is not exceptional longevity but one's function and health that may be associated with telomere length.
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lower all cause cardiovascular and cancer mortality in Centenarians offspring
Journal of the American Geriatrics Society, 2004Co-Authors: Dellara F Terry, Stacy L Andersen, Marsha A Wilcox, Maegan A Mccormick, Jaemi Pennington, Emily A Schoenhofen, Thomas T PerlsAbstract:Objectives To assess the cause of death for Centenarians' offspring and controls. Design Cross-sectional study. Setting Community-based, nationwide sample. Participants Family pedigree information was collected on 295 offspring of Centenarians (from 106 families with a parent already enrolled in the nationwide New England Centenarian Study) and on 276 controls (from 82 control families) from 1997 to 2000. Controls were individuals whose parents were born in the same year as the Centenarians but at least one of whom died at the average life expectancy. Measurements Age at death and cause of death. Results Centenarians' offspring had a 62% lower risk of all-cause mortality (P Conclusion These findings suggest that Centenarians' offspring have lower all-cause mortality rates and cause-specific mortality rates for cancer and coronary heart disease. These results suggest that mechanisms for survival to exceptional old age may go beyond the avoidance or delay of cardiovascular disease and also include the avoidance or delay of cancer. Moreover survival advantage of centenarian offsprings may not be due to factors related to childhood mortality. Ultimately, survival to exceptional old age may involve lower susceptibility to a broad range of age-related diseases, perhaps secondary to inhibition of basic mechanisms of aging.
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cardiovascular advantages among the offspring of Centenarians
Journals of Gerontology Series A-biological Sciences and Medical Sciences, 2003Co-Authors: Dellara F Terry, Marsha A Wilcox, Maegan A Mccormick, Elizabeth V Lawler, Thomas T PerlsAbstract:Background. A significant component of the ability to survive to exceptional old age may be familial. This study assessed the prevalence of age-related diseases in the offspring of Centenarians. Methods. The health histories of centenarian offspring (n = 177) and controls (n = 166) were assessed from 1997-2000 using a cross-sectional study design. The offspring of 192 centenarian subjects enrolled in the nationwide New England Centenarian Study were recruited and enrolled. Controls consisted of offspring whose parents were born in the same years as the Centenarians but at least 1 of whom died at an average life expectancy. Prevalence of age-related diseases including heart disease, hypertension, diabetes, cancer, osteoporosis, stroke, dementia, cataracts, glaucoma, macular degeneration, depression, Parkinson's disease, thyroid disease, and chronic obstructive pulmonary disease were compared between the two groups. Results. Centenarian offspring had a 56% reduced relative prevalence of heart disease (odds ratio [OR] 0.44, 95% confidence interval [Cl] 0.24, 0.80), a 66% reduced relative prevalence of hypertension (OR 0.34, 95% CI 0.21, 0.55), and 59% reduced relative prevalence of diabetes (OR 0.41, 95% CI 0.15, 1.12) after multivariate adjusted analyses. Conclusions. The offspring of Centenarians demonstrate a markedly reduced prevalence of diseases associated with aging, in particular for cardiovascular disease and cardiovascular risk factors. Along with their parents, the centenarian offspring, who are in their 70s and 80s, may prove to be a valuable cohort to study genetic and environmental factors conducive to the ability to live to very old age in good health.
Stacy L Andersen - One of the best experts on this subject based on the ideXlab platform.
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protein signatures of Centenarians and their offspring suggest Centenarians age slower than other humans
Aging Cell, 2021Co-Authors: Paola Sebastiani, Anthony Federico, Melody Morris, Anastasia Gurinovich, Toshiko Tanaka, Kevin B Chandler, Stacy L Andersen, Gerald V Denis, Catherine E Costello, Luigi FerrucciAbstract:Using samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 Centenarians, 82 Centenarians' offspring, and 65 age-matched controls of the offspring (mean ages: 105, 80, and 79 years). We identified 1312 proteins that significantly differ between Centenarians and their offspring and controls (FDR < 1%), and two different protein signatures that predict longer survival in Centenarians and in younger people. By comparing the centenarian signature with 2 independent proteomic studies of aging, we replicated the association of 484 proteins of aging and we identified two serum protein signatures that are specific of extreme old age. The data suggest that Centenarians acquire similar aging signatures as seen in younger cohorts that have short survival periods, suggesting that they do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this finding, we provide a new list of serum proteins that can be used to measure cellular senescence. Protein co-expression network analysis suggests that a small number of biological drivers may regulate aging and extreme longevity, and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging and provides specific circulating biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.
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protein signatures of Centenarians and their offspring suggest Centenarians age slower than other humans
Social Science Research Network, 2019Co-Authors: Paola Sebastiani, Anthony Federico, Melody Morris, Anastasia Gurinovich, Stacy L Andersen, Luigi Ferrucci, Tanaka Toshiko, Aparna Bhutkar, Lori L Jennings, Stefano MontiAbstract:We used a high-throughput Somascan platform to quantify 4116 proteins in the serum of 224Centenarians, offspring, and controls (mean ages: 105, 80, 79 years) from the New England Centenarian Study, and to characterize the serum proteome of aging and longevity. We identified 1312 proteins that significantly differ between Centenarians and their offspring and controls (FDR<1%), and replicated the association of 484 of these using 2 independent proteomic studies of aging. By comparing the patterns of proteins associated with aging to protein profiles of Centenarians, we also identified serum-protein signatures of extreme old age and of immune senescence. We then searched for protein signatures that distinguish between short and long survival within various age groups and we identified two differentprotein signatures that predict longer survival in older people and in Centenarians. The data suggest that Centenarians acquire similar aging patterns as seen in younger cohorts that have short survival periods, suggesting that Centenarians do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this findingwe provide a new list of serum proteins that can be used to measure cellular senescence. Consistently with this findings, protein co-expression network analysis showed that the serum proteome of offspring and controls clusters in a small number of modules of correlated proteins, some of which are conserved in Centenarians’ serum while others break down in smaller modules thus suggesting that a small number of biological drivers may regulate aging and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging, and provides specific biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.
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a serum protein signature of apoe genotypes in Centenarians
Aging Cell, 2019Co-Authors: Paola Sebastiani, Melody Morris, Anastasia Gurinovich, Stacy L Andersen, Luigi Ferrucci, Tanaka Toshiko, Lori L Jennings, Stefano Monti, Benjamin Sweigart, David J GlassAbstract:The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late-onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of APOE has a neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in Centenarians. In this study, we correlated APOE genotype data of 222 participants of the New England Centenarian Study, including 75 Centenarians, 82 centenarian offspring, and 65 controls, comprising 55 carriers of APOE e2 , with aptamer-based serum proteomics (SomaLogic technology) of 4,785 human proteins corresponding to 4,137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes and replicated the signature in three independent studies. We also show that the protein signature tracks with gene expression profiles in brains of late-onset Alzheimer's disease versus healthy controls. Finally, we show that seven of these proteins correlate with cognitive function patterns in longitudinally collected data. This analysis in particular suggests that Baculoviral IAP repeat containing two (BIRC2) is a novel biomarker of neuroprotection that associates with the neuroprotective allele of APOE. Therefore, targeting APOE e2 molecularly may preserve cognitive function.
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icc dementia international centenarian consortium dementia an international consortium to determine the prevalence and incidence of dementia in Centenarians across diverse ethnoracial and sociocultural groups
BMC Neurology, 2016Co-Authors: Henry Brodaty, Nir Barzilai, Stacy L Andersen, John D Crawford, Claudia Woolf, Carol Brayne, Karen Siu Lan Cheung, Maria M Corrada, Catriona DalyAbstract:Considerable variability exists in international prevalence and incidence estimates of dementia. The accuracy of estimates of dementia in the oldest-old and the controversial question of whether dementia incidence and prevalence decline at very old age will be crucial for better understanding the dynamics between survival to extreme old age and the occurrence and risk for various types of dementia and comorbidities. International Centenarian Consortium – Dementia (ICC-Dementia) seeks to harmonise centenarian and near-centenarian studies internationally to describe the cognitive and functional profiles of exceptionally old individuals, and ascertain the trajectories of decline and thereby the age-standardised prevalence and incidence of dementia in this population. The primary goal of the ICC-Dementia is to establish a large and thorough heterogeneous sample that has the power to answer epidemiological questions that small, separate studies cannot. A secondary aim is to examine cohort-specific effects and differential survivorship into very old age. We hope to lay the foundation for further investigation into risk and protective factors for dementia and healthy exceptional brain ageing in Centenarians across diverse ethnoracial and sociocultural groups. Studies focusing on individuals aged ≥95 years (approximately the oldest 1 percentile for men, oldest 5th percentile for women), with a minimum sample of 80 individuals, including assessment of cognition and functional status, are invited to participate. There are currently seventeen member or potential member studies from Asia, Europe, the Americas, and Oceania. Initial attempts at harmonising key variables are in progress. General challenges facing large, international consortia like ICC-Dementia include timely and effective communication among member studies, ethical and practical issues relating to human subject studies and data sharing, and the challenges related to data harmonisation. A specific challenge for ICC-Dementia relates to the concept and definition of’abnormal’ in this exceptional group of individuals who are rarely free of physical, sensory and/or cognitive impairments.
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association of longer telomeres with better health in Centenarians
Journals of Gerontology Series A-biological Sciences and Medical Sciences, 2008Co-Authors: Dellara F Terry, Stacy L Andersen, Thomas T Perls, Vikki G Nolan, Richard M CawthonAbstract:Prior animal model studies have demonstrated an association between telomere length and longevity. Our study examines telomere length in Centenarians in good health versus poor health. Using DNA from blood lymphocytes, telomere length was measured by quantitative polymerase chain reaction in 38 sex- and age-matched Centenarians (ages 97-108). "Healthy" Centenarians (n = 19) with physical function in the independent range and the absence of hypertension, congestive heart failure, myocardial infarction, peripheral vascular disease, dementia, cancer, stroke, chronic obstructive pulmonary disease, and diabetes were compared to Centenarians with physical function limitations and > or =2 of the above conditions (n = 19). Healthy Centenarians had significantly longer telomeres than did unhealthy Centenarians (p =.0475). Our study demonstrated that investigations of the association between telomere length and exceptional longevity must take into account the health status of the individuals. This raises the possibility that perhaps it is not exceptional longevity but one's function and health that may be associated with telomere length.
Paola Sebastiani - One of the best experts on this subject based on the ideXlab platform.
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protein signatures of Centenarians and their offspring suggest Centenarians age slower than other humans
Aging Cell, 2021Co-Authors: Paola Sebastiani, Anthony Federico, Melody Morris, Anastasia Gurinovich, Toshiko Tanaka, Kevin B Chandler, Stacy L Andersen, Gerald V Denis, Catherine E Costello, Luigi FerrucciAbstract:Using samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 Centenarians, 82 Centenarians' offspring, and 65 age-matched controls of the offspring (mean ages: 105, 80, and 79 years). We identified 1312 proteins that significantly differ between Centenarians and their offspring and controls (FDR < 1%), and two different protein signatures that predict longer survival in Centenarians and in younger people. By comparing the centenarian signature with 2 independent proteomic studies of aging, we replicated the association of 484 proteins of aging and we identified two serum protein signatures that are specific of extreme old age. The data suggest that Centenarians acquire similar aging signatures as seen in younger cohorts that have short survival periods, suggesting that they do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this finding, we provide a new list of serum proteins that can be used to measure cellular senescence. Protein co-expression network analysis suggests that a small number of biological drivers may regulate aging and extreme longevity, and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging and provides specific circulating biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.
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protein signatures of Centenarians and their offspring suggest Centenarians age slower than other humans
Social Science Research Network, 2019Co-Authors: Paola Sebastiani, Anthony Federico, Melody Morris, Anastasia Gurinovich, Stacy L Andersen, Luigi Ferrucci, Tanaka Toshiko, Aparna Bhutkar, Lori L Jennings, Stefano MontiAbstract:We used a high-throughput Somascan platform to quantify 4116 proteins in the serum of 224Centenarians, offspring, and controls (mean ages: 105, 80, 79 years) from the New England Centenarian Study, and to characterize the serum proteome of aging and longevity. We identified 1312 proteins that significantly differ between Centenarians and their offspring and controls (FDR<1%), and replicated the association of 484 of these using 2 independent proteomic studies of aging. By comparing the patterns of proteins associated with aging to protein profiles of Centenarians, we also identified serum-protein signatures of extreme old age and of immune senescence. We then searched for protein signatures that distinguish between short and long survival within various age groups and we identified two differentprotein signatures that predict longer survival in older people and in Centenarians. The data suggest that Centenarians acquire similar aging patterns as seen in younger cohorts that have short survival periods, suggesting that Centenarians do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this findingwe provide a new list of serum proteins that can be used to measure cellular senescence. Consistently with this findings, protein co-expression network analysis showed that the serum proteome of offspring and controls clusters in a small number of modules of correlated proteins, some of which are conserved in Centenarians’ serum while others break down in smaller modules thus suggesting that a small number of biological drivers may regulate aging and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging, and provides specific biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.
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a serum protein signature of apoe genotypes in Centenarians
Innovation in Aging, 2019Co-Authors: Stefano Monti, Paola Sebastiani, Anastasia Gurinovich, Toshiko Tanaka, Lori L Jennings, David J Glass, Thomas T PerlsAbstract:The discovery of treatments to prevent or delay Alzheimer’s disease is a priority. The gene APOE is associated with cognitive change and late onset Alzheimer’s disease, and epidemiological studies have shown that the e_2 allele of APOE has a neuroprotective effect, and it is associated with increased longevity. We correlated APOE genotype data of 222 New England Centenarian Study participants, including 79 Centenarians, 84 centenarian offspring and 55 carriers of APOE e_2, with aptamer-based serum proteomics (SomaLogic technology) of 4783 human proteins corresponding to 4137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes, and replicated the signature in 3 independent studies. We show that the protein signature tracks with gene expression profiles in brains of late onset Alzheimer’s disease vs. healthy controls. Finally, we show that seven of these proteins correlate with cognitive function changes. Therefore, targeting APOE e_2 molecularly may preserve cognitive function.
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a serum protein signature of apoe genotypes in Centenarians
Aging Cell, 2019Co-Authors: Paola Sebastiani, Melody Morris, Anastasia Gurinovich, Stacy L Andersen, Luigi Ferrucci, Tanaka Toshiko, Lori L Jennings, Stefano Monti, Benjamin Sweigart, David J GlassAbstract:The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late-onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of APOE has a neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in Centenarians. In this study, we correlated APOE genotype data of 222 participants of the New England Centenarian Study, including 75 Centenarians, 82 centenarian offspring, and 65 controls, comprising 55 carriers of APOE e2 , with aptamer-based serum proteomics (SomaLogic technology) of 4,785 human proteins corresponding to 4,137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes and replicated the signature in three independent studies. We also show that the protein signature tracks with gene expression profiles in brains of late-onset Alzheimer's disease versus healthy controls. Finally, we show that seven of these proteins correlate with cognitive function patterns in longitudinally collected data. This analysis in particular suggests that Baculoviral IAP repeat containing two (BIRC2) is a novel biomarker of neuroprotection that associates with the neuroprotective allele of APOE. Therefore, targeting APOE e2 molecularly may preserve cognitive function.
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personality traits of Centenarians offspring
Journal of the American Geriatrics Society, 2009Co-Authors: Jane L Givens, Paola Sebastiani, Dellara F Terry, Margery Silver, Maureen Frederick, Leanne Silverman, Stacy Anderson, Joanna Senville, Paul T Costa, Thomas T PerlsAbstract:Research on siblings and offspring of Centenarians has documented that exceptional longevity runs strongly in families.1–4 Studies of the offspring of Centenarians have shown that their mortality is lower that that of other members of their birth cohort5 and that they have lower prevalence1,6 and delayed onset of cardiovascular disease, hypertension, and diabetes mellitus.7 Thus, they are regarded as a model of healthy aging. Because personality traits have been shown to have substantial heritable components, 8 it was hypothesized that certain personality features may be important to the healthy aging observed in the offspring of Centenarians. Several studies have assessed the effect of personality traits on survival using the Five-Factor Model (FFM) of Personality. Studies have used the Revised NEO Personality Inventory, a 240-item measure of the five broad factors and the 30 narrower facet scales or the NEO Five-Factor Inventory (NEO-FFI), a 60-item self-report questionnaire that measures only the five personality factors: neuroticism (emotional reactivity and distress), extraversion (tendency to be outgoing, active), openness (flexibility and openness to new ideas), agreeableness (cooperation and empathy), and conscientiousness (social responsibility and self-discipline).9 Findings from longitudinal studies have, to some extent, been consistent, indicating that high conscientiousness, low neuroticism, and perhaps high extraversion are predictive of lower mortality and longevity in aging populations.10–13 Prior research suggests that offspring of Centenarians are a model of healthy aging and that certain personality traits are associated with mortality and longevity. Thus, this study aimed to test the hypothesis that above-average levels of health-promoting traits (e.g., conscientiousness and extraversion) and below-average levels of health-damaging traits (e.g., neuroticism) characterize offspring of Centenarians. Using the NEO-FFI from the FFM, this study set out to measure the personality characteristics of offspring of Centenarians and to compare NEO-FFI scores of Centenarians’ offspring with normative scores.
Luigi Ferrucci - One of the best experts on this subject based on the ideXlab platform.
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protein signatures of Centenarians and their offspring suggest Centenarians age slower than other humans
Aging Cell, 2021Co-Authors: Paola Sebastiani, Anthony Federico, Melody Morris, Anastasia Gurinovich, Toshiko Tanaka, Kevin B Chandler, Stacy L Andersen, Gerald V Denis, Catherine E Costello, Luigi FerrucciAbstract:Using samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 Centenarians, 82 Centenarians' offspring, and 65 age-matched controls of the offspring (mean ages: 105, 80, and 79 years). We identified 1312 proteins that significantly differ between Centenarians and their offspring and controls (FDR < 1%), and two different protein signatures that predict longer survival in Centenarians and in younger people. By comparing the centenarian signature with 2 independent proteomic studies of aging, we replicated the association of 484 proteins of aging and we identified two serum protein signatures that are specific of extreme old age. The data suggest that Centenarians acquire similar aging signatures as seen in younger cohorts that have short survival periods, suggesting that they do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this finding, we provide a new list of serum proteins that can be used to measure cellular senescence. Protein co-expression network analysis suggests that a small number of biological drivers may regulate aging and extreme longevity, and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging and provides specific circulating biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.
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protein signatures of Centenarians and their offspring suggest Centenarians age slower than other humans
Social Science Research Network, 2019Co-Authors: Paola Sebastiani, Anthony Federico, Melody Morris, Anastasia Gurinovich, Stacy L Andersen, Luigi Ferrucci, Tanaka Toshiko, Aparna Bhutkar, Lori L Jennings, Stefano MontiAbstract:We used a high-throughput Somascan platform to quantify 4116 proteins in the serum of 224Centenarians, offspring, and controls (mean ages: 105, 80, 79 years) from the New England Centenarian Study, and to characterize the serum proteome of aging and longevity. We identified 1312 proteins that significantly differ between Centenarians and their offspring and controls (FDR<1%), and replicated the association of 484 of these using 2 independent proteomic studies of aging. By comparing the patterns of proteins associated with aging to protein profiles of Centenarians, we also identified serum-protein signatures of extreme old age and of immune senescence. We then searched for protein signatures that distinguish between short and long survival within various age groups and we identified two differentprotein signatures that predict longer survival in older people and in Centenarians. The data suggest that Centenarians acquire similar aging patterns as seen in younger cohorts that have short survival periods, suggesting that Centenarians do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this findingwe provide a new list of serum proteins that can be used to measure cellular senescence. Consistently with this findings, protein co-expression network analysis showed that the serum proteome of offspring and controls clusters in a small number of modules of correlated proteins, some of which are conserved in Centenarians’ serum while others break down in smaller modules thus suggesting that a small number of biological drivers may regulate aging and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging, and provides specific biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.
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a serum protein signature of apoe genotypes in Centenarians
Aging Cell, 2019Co-Authors: Paola Sebastiani, Melody Morris, Anastasia Gurinovich, Stacy L Andersen, Luigi Ferrucci, Tanaka Toshiko, Lori L Jennings, Stefano Monti, Benjamin Sweigart, David J GlassAbstract:The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late-onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of APOE has a neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in Centenarians. In this study, we correlated APOE genotype data of 222 participants of the New England Centenarian Study, including 75 Centenarians, 82 centenarian offspring, and 65 controls, comprising 55 carriers of APOE e2 , with aptamer-based serum proteomics (SomaLogic technology) of 4,785 human proteins corresponding to 4,137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes and replicated the signature in three independent studies. We also show that the protein signature tracks with gene expression profiles in brains of late-onset Alzheimer's disease versus healthy controls. Finally, we show that seven of these proteins correlate with cognitive function patterns in longitudinally collected data. This analysis in particular suggests that Baculoviral IAP repeat containing two (BIRC2) is a novel biomarker of neuroprotection that associates with the neuroprotective allele of APOE. Therefore, targeting APOE e2 molecularly may preserve cognitive function.
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do men and women follow different trajectories to reach extreme longevity italian multicenter study on Centenarians imusce
Aging Clinical and Experimental Research, 2000Co-Authors: Claudio Franceschi, Luciano Motta, Massimiliano Bonafè, Daniela Monti, Silvana Valensin, R Rapisarda, A M Franzone, M Berardelli, Maurizio Motta, Luigi FerrucciAbstract:Gender accounts for important differences in the incidence and prevalence of a variety of age-related diseases. Considering people of far advanced age, demographic data document a clear-cut prevalence of females compared to males, suggesting that sex-specific mortality rates follow different trajectories during aging. In the present investigation, we report data from a nationwide study on Italian Centenarians (a total of 1162 subjects), and from two studies on Centenarians living in two distinct zones of Italy, i.e., the island of Sardinia (a total of 222 subjects) and the Mantova province (Northern Italy) (a total of 43 subjects). The female/male ratio was about 2:1 in Sardinia, 4:1 in the whole of Italy, and about 7:1 in the Mantova province. Thus, a complex interaction of environmental, historical and genetic factors, differently characterizing the various parts of Italy, likely plays an important role in determining the gender-specific probability of achieving longevity. Gender differences in the health status of Centenarians are also reported, and an innovative score method to classify long-lived people in different health categories, according to clinical and functional parameters, is proposed. Our data indicate that not only is this selected group of people, as a whole, highly heterogeneous, but also that a marked gender difference exists, since male Centenarians are less heterogeneous and more healthy than female Centenarians. Immunological factors regarding the age-related increase in pro-inflammatory status, and the frequency of HLA ancestral haplotypes also show gender differences that likely contribute to the different strategies that men and women seem to follow to achieve longevity. Concerning the different impact of genetic factors on the probability of reaching the extreme limits of the human life-span, emerging evidence (regarding mtDNA haplogroups, Thyrosine Hydroxilase, and IL-6 genes) suggests that female longevity is less dependent on genetics than male longevity, and that female Centenarians likely exploited a healthier life-style and more favorable environmental conditions, owing to gender-specific cultural and anthropological characteristics of the Italian society in the last 100 years.
Stefano Monti - One of the best experts on this subject based on the ideXlab platform.
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protein signatures of Centenarians and their offspring suggest Centenarians age slower than other humans
Social Science Research Network, 2019Co-Authors: Paola Sebastiani, Anthony Federico, Melody Morris, Anastasia Gurinovich, Stacy L Andersen, Luigi Ferrucci, Tanaka Toshiko, Aparna Bhutkar, Lori L Jennings, Stefano MontiAbstract:We used a high-throughput Somascan platform to quantify 4116 proteins in the serum of 224Centenarians, offspring, and controls (mean ages: 105, 80, 79 years) from the New England Centenarian Study, and to characterize the serum proteome of aging and longevity. We identified 1312 proteins that significantly differ between Centenarians and their offspring and controls (FDR<1%), and replicated the association of 484 of these using 2 independent proteomic studies of aging. By comparing the patterns of proteins associated with aging to protein profiles of Centenarians, we also identified serum-protein signatures of extreme old age and of immune senescence. We then searched for protein signatures that distinguish between short and long survival within various age groups and we identified two differentprotein signatures that predict longer survival in older people and in Centenarians. The data suggest that Centenarians acquire similar aging patterns as seen in younger cohorts that have short survival periods, suggesting that Centenarians do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this findingwe provide a new list of serum proteins that can be used to measure cellular senescence. Consistently with this findings, protein co-expression network analysis showed that the serum proteome of offspring and controls clusters in a small number of modules of correlated proteins, some of which are conserved in Centenarians’ serum while others break down in smaller modules thus suggesting that a small number of biological drivers may regulate aging and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging, and provides specific biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.
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a serum protein signature of apoe genotypes in Centenarians
Innovation in Aging, 2019Co-Authors: Stefano Monti, Paola Sebastiani, Anastasia Gurinovich, Toshiko Tanaka, Lori L Jennings, David J Glass, Thomas T PerlsAbstract:The discovery of treatments to prevent or delay Alzheimer’s disease is a priority. The gene APOE is associated with cognitive change and late onset Alzheimer’s disease, and epidemiological studies have shown that the e_2 allele of APOE has a neuroprotective effect, and it is associated with increased longevity. We correlated APOE genotype data of 222 New England Centenarian Study participants, including 79 Centenarians, 84 centenarian offspring and 55 carriers of APOE e_2, with aptamer-based serum proteomics (SomaLogic technology) of 4783 human proteins corresponding to 4137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes, and replicated the signature in 3 independent studies. We show that the protein signature tracks with gene expression profiles in brains of late onset Alzheimer’s disease vs. healthy controls. Finally, we show that seven of these proteins correlate with cognitive function changes. Therefore, targeting APOE e_2 molecularly may preserve cognitive function.
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a serum protein signature of apoe genotypes in Centenarians
Aging Cell, 2019Co-Authors: Paola Sebastiani, Melody Morris, Anastasia Gurinovich, Stacy L Andersen, Luigi Ferrucci, Tanaka Toshiko, Lori L Jennings, Stefano Monti, Benjamin Sweigart, David J GlassAbstract:The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late-onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of APOE has a neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in Centenarians. In this study, we correlated APOE genotype data of 222 participants of the New England Centenarian Study, including 75 Centenarians, 82 centenarian offspring, and 65 controls, comprising 55 carriers of APOE e2 , with aptamer-based serum proteomics (SomaLogic technology) of 4,785 human proteins corresponding to 4,137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes and replicated the signature in three independent studies. We also show that the protein signature tracks with gene expression profiles in brains of late-onset Alzheimer's disease versus healthy controls. Finally, we show that seven of these proteins correlate with cognitive function patterns in longitudinally collected data. This analysis in particular suggests that Baculoviral IAP repeat containing two (BIRC2) is a novel biomarker of neuroprotection that associates with the neuroprotective allele of APOE. Therefore, targeting APOE e2 molecularly may preserve cognitive function.