Thomas T. Perls
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View article: A Robust Serum Proteomic Signature of the E2 Allele of Apolipoprotein E
A Robust Serum Proteomic Signature of the E2 Allele of Apolipoprotein E Open
A signature of 16 serum proteins that were previously profiled using the aptamer‐based Somascan technology highlighted the roles of the e2 allele of APOE in lipid regulation via apolipoprotein B (APOB) and apolipoprotein E (APOE) and in in…
View article: IPSC-based modeling of resiliency in centenarians reveals longevity-specific signatures
IPSC-based modeling of resiliency in centenarians reveals longevity-specific signatures Open
Centenarians represent a human model of resilience to age-related decline, yet resiliency mechanisms remain elusive. Here, we establish an induced pluripotent stem cell (iPSC)-based platform to interrogate resilience signatures in centenar…
View article: The role of lipids in the effect of APOE2 on cognitive function: a causal mediation analysis
The role of lipids in the effect of APOE2 on cognitive function: a causal mediation analysis Open
Extensive research has examined the direct effect of APOE alleles on cognitive decline. However, there is limited investigation into the effect of APOE that is explained or mediated through molecular pathways, such as lipids. In this study…
View article: Pathway analysis of cognitive resilience factors and cognitive function in the Long Life Family Study (LLFS).
Pathway analysis of cognitive resilience factors and cognitive function in the Long Life Family Study (LLFS). Open
These results suggest that familial longevity and engagement in cognitively stimulating activities represent two distinct pathways that contribute to preserved cognition in older adulthood, though these findings should be replicated in mor…
View article: Metabolomic Signatures of Extreme Old Age: Findings from the New England Centenarian Study
Metabolomic Signatures of Extreme Old Age: Findings from the New England Centenarian Study Open
The New England Centenarian Study (NECS) provides a unique resource for the study of extreme human longevity (EL). To gain insight into biological pathways related to EL, chronological age and survival, we used an untargeted serum metabolo…
View article: Utility of Polygenic Risk Scores in Families with Exceptional Longevity
Utility of Polygenic Risk Scores in Families with Exceptional Longevity Open
Introduction Polygenic risk scores (PRS) have been used to assess an individual’s risk for various diseases, including Alzheimer’s disease (AD). This study applied the PRS approach to a cohort of families ascertained for healthy aging, tha…
View article: Whole blood transcriptional signatures of age and survival identified in Long Life Family and Integrative Longevity Omics Studies
Whole blood transcriptional signatures of age and survival identified in Long Life Family and Integrative Longevity Omics Studies Open
Background Age is one of the major risk factors for a wide range of diseases. Nevertheless, some individuals can better cope with these changes and become centenarians. We hypothesize that their blood transcriptome may provide insights int…
View article: Increased Genetic Protection Against Alzheimer’s Disease in Centenarians
Increased Genetic Protection Against Alzheimer’s Disease in Centenarians Open
We constructed a polygenic protective score specific to Alzheimer’s disease (AD PPS) based on the current literature among the participants enrolled in five studies of healthy aging and extreme longevity in the US, Europe, and Asia. This A…
View article: Robust Serum Proteomic Signatures of APOE2
Robust Serum Proteomic Signatures of APOE2 Open
We previously identified a signature of 16 serum proteins that highlighted a role of the e2 allele of APOE in lipid regulation via apolipoprotein B (APOB) and apolipoprotein E (APOE), and in inflammation. The serum proteins were profiled u…
View article: Integrative analysis across metagenomic taxonomic classifiers: A case study of the gut microbiome in aging and longevity
Integrative analysis across metagenomic taxonomic classifiers: A case study of the gut microbiome in aging and longevity Open
SUMMARY Despite calls for the development of consensus methods, most analyses of shotgun metagenomics data for microbiome studies use a single taxonomic classifier. In this study, we compare inferences from two broadly used classifiers, Me…
View article: Evidence of a novel gene locus <i>ARHGAP44</i> for longitudinal change in hemoglobin A1c levels among subjects without diabetes from the Long Life Family Study
Evidence of a novel gene locus <i>ARHGAP44</i> for longitudinal change in hemoglobin A1c levels among subjects without diabetes from the Long Life Family Study Open
HbA1c is clinically used in T2D diagnosis and monitoring. Its longitudinal change (ΔHbA1c) is associated with T2D-related aging processes and mortality. Targeted association tests under significant linkage peaks in extended families permit…
View article: Causal mediation analysis of the neuroprotection of<i>APOE2</i>through lipid pathways
Causal mediation analysis of the neuroprotection of<i>APOE2</i>through lipid pathways Open
Background Recent studies have revealed a strong association between the e2 allele of the Apolipoprotein E ( APOE2) gene and lipid metabolites. In addition, APOE2 carriers appear to be protected from cognitive decline and Alzheimer’s disea…
View article: SNP rs6543176 is associated with extreme human longevity but increased risk for cancer
SNP rs6543176 is associated with extreme human longevity but increased risk for cancer Open
View article: Additional Cover
Additional Cover Open
Cover legend: The cover image is based on the article A longevity‐specific bank of induced pluripotent stem cells from centenarians and their offspring by George Murphy et al., https://doi.org/10.1111/acel.14351. [Image: see text]
View article: Metabolite signatures of chronological age, aging, survival, and longevity
Metabolite signatures of chronological age, aging, survival, and longevity Open
View article: A longevity‐specific bank of induced pluripotent stem cells from centenarians and their offspring
A longevity‐specific bank of induced pluripotent stem cells from centenarians and their offspring Open
Centenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models of human aging and resilience to disease that allow for the testing of potential interventions are virtually non‐existent.…
View article: Cross-platform proteomics signatures of extreme old age
Cross-platform proteomics signatures of extreme old age Open
View article: Estimating treatment effects from observational data under truncation by death using survival-incorporated quantiles
Estimating treatment effects from observational data under truncation by death using survival-incorporated quantiles Open
The issue of "truncation by death" commonly arises in clinical research: subjects may die before their follow-up assessment, resulting in undefined clinical outcomes. To address this issue, we focus on survival-incorporated quantiles -- qu…
View article: Adherence to the Alternative Health Eating Index and Planetary Health Diet Index in the New England Centenarian Study
Adherence to the Alternative Health Eating Index and Planetary Health Diet Index in the New England Centenarian Study Open
View article: A Novel Gene<i>ARHGAP44</i>for Longitudinal Changes in Glycated Hemoglobin (HbA1c) in Subjects without Type 2 Diabetes: Evidence from the Long Life Family Study (LLFS) and the Framingham Offspring Study (FOS)
A Novel Gene<i>ARHGAP44</i>for Longitudinal Changes in Glycated Hemoglobin (HbA1c) in Subjects without Type 2 Diabetes: Evidence from the Long Life Family Study (LLFS) and the Framingham Offspring Study (FOS) Open
Glycated hemoglobin (HbA1c) indicates average glucose levels over three months and is associated with insulin resistance and type 2 diabetes (T2D). Longitudinal changes in HbA1c (ΔHbA1c) are also associated with aging processes, cognitive …
View article: Cross-platform proteomics signatures of extreme old age
Cross-platform proteomics signatures of extreme old age Open
In previous work we used a Somalogic platform targeting approximately 5000 proteins to generate a serum protein signature of centenarians that we validated in independent studies that used the same technology. We set here to validate and p…
View article: A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring
A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring Open
Centenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models of human aging and resilience to disease that allow for the testing of potential interventions are virtually non-existent.…
View article: The relationship between 11 different polygenic longevity scores, parental lifespan, and disease diagnosis in the UK Biobank
The relationship between 11 different polygenic longevity scores, parental lifespan, and disease diagnosis in the UK Biobank Open
Large-scale genome-wide association studies (GWAS) strongly suggest that most traits and diseases have a polygenic component. This observation has motivated the development of disease-specific “polygenic scores (PGS)” that are weighted sum…
View article: Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies <i>MTUS2</i> gene associated with late‐onset Alzheimer's disease
Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies <i>MTUS2</i> gene associated with late‐onset Alzheimer's disease Open
INTRODUCTION Late‐onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long‐Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics. METHODS We cond…
View article: Examination of Genetic Risk Factors for Alzheimer’s Disease in a Cohort of Familial Longevity: the Long Life Family Study
Examination of Genetic Risk Factors for Alzheimer’s Disease in a Cohort of Familial Longevity: the Long Life Family Study Open
Background Genetic risk factors have been explored extensively for late onset Alzheimer’s Disease (LOAD). The largest meta‐analysis GWAS studies to date (Bellenguez et al., 2022) identified 83 single nucleotide polymorphisms (SNPs) associa…
View article: DISTANCE-BASED ANALYSIS OF LONGEVITY-RELATED METABOLOMIC PROFILES
DISTANCE-BASED ANALYSIS OF LONGEVITY-RELATED METABOLOMIC PROFILES Open
Longevity is a complex multifactorial trait with many interacting determinants. Identifying each determinant is complicated given that the marginal effect of any one of them may be small. Contemporary high-throughput biomedical assays, suc…
View article: SERUM METABOLOMICS SIGNATURES OF EXTREME OLD AGE AND LONGEVITY
SERUM METABOLOMICS SIGNATURES OF EXTREME OLD AGE AND LONGEVITY Open
A total of 1,495 chemicals including 1,213 compounds of known identity and 282 compounds of unknown structural identity were profiled in serum samples collected at enrollment at Metabolon, Inc. from the blood serum of 213 subjects, includi…
View article: TRANSCRIPTOMIC SIGNATURES FOR AGING AND EXTREME OLD AGE IDENTIFIED IN THE LONG LIFE FAMILY STUDY
TRANSCRIPTOMIC SIGNATURES FOR AGING AND EXTREME OLD AGE IDENTIFIED IN THE LONG LIFE FAMILY STUDY Open
Transcriptional studies of blood have previously identified changes in gene expression profiles associated with age. Centenarians, a rare population of individuals that reach 100 years of age, experience delays in aging-related diseases an…
View article: METABOLOMIC SIGNATURES OF AGE, EXTREME OLD AGE, AND LONGEVITY IN LONG LIFE FAMILY STUDY PARTICIPANTS
METABOLOMIC SIGNATURES OF AGE, EXTREME OLD AGE, AND LONGEVITY IN LONG LIFE FAMILY STUDY PARTICIPANTS Open
Serum metabolomics of aging has been a growing area of interest and several studies have identified metabolites that correlate with chronological age. The Long Life Family Study (LLFS) has generated serum metabolomics of individuals aged 3…
View article: TRANSCRIPTOMIC SIGNATURES FOR AGING AND EXTREME OLD AGE IDENTIFIED IN LONG LIFE FAMILY STUDY
TRANSCRIPTOMIC SIGNATURES FOR AGING AND EXTREME OLD AGE IDENTIFIED IN LONG LIFE FAMILY STUDY Open
Transcriptional studies of blood have previously identified changes in gene expression profiles associated with age. Centenarians, a rare population of individuals that reach 100 years of age, experience delays in aging-related diseases an…