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Artikel ; Online: Assessment of Epigenetic Clocks as Biomarkers of Aging in Basic and Population Research.

Levine, Morgan E

The journals of gerontology. Series A, Biological sciences and medical sciences

2020 Band 75, Heft 3, Seite(n) 463–465

Mesh-Begriff(e)	Aging/genetics ; Aging/metabolism ; Biomedical Research ; DNA Methylation ; Epigenesis, Genetic ; Humans
Sprache	Englisch
Erscheinungsdatum	2020-01-17
Erscheinungsland	United States
Dokumenttyp	Editorial
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glaa021
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Age-Invariant Genes: Multi-Tissue Identification and Characterization of Murine Reference Genes.

González, John T / Thrush, Kyra / Meer, Margarita / Levine, Morgan E / Higgins-Chen, Albert T

bioRxiv : the preprint server for biology

2024

Abstract: Studies of the aging transcriptome focus on genes that change with age. But what can we learn from age-invariant genes-those that remain unchanged throughout the aging process? These genes also have a practical application: they serve as reference genes ( ...

Abstract	Studies of the aging transcriptome focus on genes that change with age. But what can we learn from age-invariant genes-those that remain unchanged throughout the aging process? These genes also have a practical application: they serve as reference genes (often called housekeeping genes) in expression studies. Reference genes have mostly been identified and validated in young organisms, and no systematic investigation has been done across the lifespan. Here, we build upon a common pipeline for identifying reference genes in RNA-seq datasets to identify age-invariant genes across seventeen C57BL/6 mouse tissues (brain, lung, bone marrow, muscle, white blood cells, heart, small intestine, kidney, liver, pancreas, skin, brown, gonadal, marrow, and subcutaneous adipose tissue) spanning 1 to 21+ months of age. We identify 9 pan-tissue age-invariant genes and many tissue-specific age-invariant genes. These genes are stable across the lifespan and are validated in independent bulk RNA-seq datasets and RT-qPCR. We find age-invariant genes have shorter transcripts on average and are enriched for CpG islands. Interestingly, pathway enrichment analysis for age-invariant genes identifies an overrepresentation of molecular functions associated with some, but not all, hallmarks of aging. Thus, though hallmarks of aging typically involve changes in cell maintenance mechanisms, select genes associated with these hallmarks resist fluctuations in expression with age. Finally, our analysis concludes no classical reference gene is appropriate for aging studies in all tissues. Instead, we provide tissue-specific and pan-tissue genes for assays utilizing reference gene normalization (i.e., RT-qPCR) that can be applied to animals across the lifespan.
Sprache	Englisch
Erscheinungsdatum	2024-04-13
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2024.04.09.588721
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Is 60 the New 50? Examining Changes in Biological Age Over the Past Two Decades.

Levine, Morgan E / Crimmins, Eileen M

Demography

2018 Band 55, Heft 2, Seite(n) 387–402

Abstract: Increasing life expectancy has been interpreted as improving health of a population. However, mortality is not always a reliable proxy for the pace of aging and could instead reflect achievement in keeping ailing people alive. Using data from NHANES III ( ...

Abstract	Increasing life expectancy has been interpreted as improving health of a population. However, mortality is not always a reliable proxy for the pace of aging and could instead reflect achievement in keeping ailing people alive. Using data from NHANES III (1988-1994) and NHANES IV (2007-2010), we examined how biological age, relative to chronological age, changed in the United States between 1988 and 2010, while estimating the contribution of changes in modifiable health behaviors. Results suggest that biological age is lower for more recent periods; however, the degree of improvement varied across age and sex groups. Overall, older adults experienced the greatest improvement or decreases in biological age. Males, especially those in the youngest and oldest groups, experienced greater declines in biological age than females. These differences were partially explained by age- and sex-specific changes in behaviors, such as smoking, obesity, and medication use. Slowing the pace of aging, along with increasing life expectancy, has important social and economic implications; thus, identifying modifiable risk factors that contribute to cohort differences in health and aging is essential.
Mesh-Begriff(e)	Adult ; Age Factors ; Aged ; Aging ; Anticholesteremic Agents/administration & dosage ; Antihypertensive Agents/administration & dosage ; Female ; Health Behavior ; Humans ; Life Expectancy/trends ; Male ; Middle Aged ; Nutrition Surveys ; Obesity/epidemiology ; Racial Groups ; Risk Factors ; Sex Factors ; Smoking/epidemiology ; Socioeconomic Factors ; United States/epidemiology ; Young Adult
Chemische Substanzen	Anticholesteremic Agents ; Antihypertensive Agents
Sprache	Englisch
Erscheinungsdatum	2018-03-05
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	280612-5
ISSN	1533-7790 ; 0070-3370
ISSN (online)	1533-7790
ISSN	0070-3370
DOI	10.1007/s13524-017-0644-5
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Response to Dr. Mitnitski's and Dr. Rockwood's letter to the editor: Biological age revisited.

Levine, Morgan E

The journals of gerontology. Series A, Biological sciences and medical sciences

2013 Band 69, Heft 3, Seite(n) 297–298

Mesh-Begriff(e)	Aging ; Biomarkers ; Female ; Humans ; Male ; Models, Theoretical
Chemische Substanzen	Biomarkers
Sprache	Englisch
Erscheinungsdatum	2013-10-10
Erscheinungsland	United States
Dokumenttyp	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glt138
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Aging biomarkers and the brain.

Higgins-Chen, Albert T / Thrush, Kyra L / Levine, Morgan E

Seminars in cell & developmental biology

2021 Band 116, Seite(n) 180–193

Abstract: Quantifying biological aging is critical for understanding why aging is the primary driver of morbidity and mortality and for assessing novel therapies to counter pathological aging. In the past decade, many biomarkers relevant to brain aging have been ... ...

Abstract	Quantifying biological aging is critical for understanding why aging is the primary driver of morbidity and mortality and for assessing novel therapies to counter pathological aging. In the past decade, many biomarkers relevant to brain aging have been developed using various data types and modeling techniques. Aging involves numerous interconnected processes, and thus many complementary biomarkers are needed, each capturing a different slice of aging biology. Here we present a hierarchical framework highlighting how these biomarkers are related to each other and the underlying biological processes. We review those measures most studied in the context of brain aging: epigenetic clocks, proteomic clocks, and neuroimaging age predictors. Many studies have linked these biomarkers to cognition, mental health, brain structure, and pathology during aging. We also delve into the challenges and complexities in interpreting these biomarkers and suggest areas for further innovation. Ultimately, a robust mechanistic understanding of these biomarkers will be needed to effectively intervene in the aging process to prevent and treat age-related disease.
Mesh-Begriff(e)	Aged ; Aged, 80 and over ; Aging/physiology ; Biomarkers/metabolism ; Brain/physiopathology ; Humans
Chemische Substanzen	Biomarkers
Sprache	Englisch
Erscheinungsdatum	2021-01-25
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2021.01.003
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Epigenetic-based age acceleration in a representative sample of older Americans: Associations with aging-related morbidity and mortality.

Faul, Jessica D / Kim, Jung Ki / Levine, Morgan E / Thyagarajan, Bharat / Weir, David R / Crimmins, Eileen M

Proceedings of the National Academy of Sciences of the United States of America

2023 Band 120, Heft 9, Seite(n) e2215840120

Abstract: Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors of health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits within the context of known socioeconomic and behavioral ... ...

Abstract	Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors of health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits within the context of known socioeconomic and behavioral associations with aging-related health outcomes in a large, population-based, and diverse sample. This study uses data from a representative, panel study of US older adults to examine the relationship between DNAm-based age acceleration measures in the prediction of cross-sectional and longitudinal health outcomes and mortality. We examine whether recent improvements to these scores, using principal component (PC)-based measures designed to remove some of the technical noise and unreliability in measurement, improve the predictive capability of these measures. We also examine how well DNAm-based measures perform against well-known predictors of health outcomes such as demographics, SES, and health behaviors. In our sample, age acceleration calculated using "second and third generation clocks," PhenoAge, GrimAge, and DunedinPACE, is consistently a significant predictor of health outcomes including cross-sectional cognitive dysfunction, functional limitations and chronic conditions assessed 2 y after DNAm measurement, and 4-y mortality. PC-based epigenetic age acceleration measures do not significantly change the relationship of DNAm-based age acceleration measures to health outcomes or mortality compared to earlier versions of these measures. While the usefulness of DNAm-based age acceleration as a predictor of later life health outcomes is quite clear, other factors such as demographics, SES, mental health, and health behaviors remain equally, if not more robust, predictors of later life outcomes.
Mesh-Begriff(e)	Humans ; Aged ; Epigenesis, Genetic ; Cross-Sectional Studies ; Aging/genetics ; DNA Methylation ; Biomarkers ; Acceleration
Chemische Substanzen	Biomarkers
Sprache	Englisch
Erscheinungsdatum	2023-02-21
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2215840120
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Modeling the rate of senescence: can estimated biological age predict mortality more accurately than chronological age?

Levine, Morgan E

The journals of gerontology. Series A, Biological sciences and medical sciences

2012 Band 68, Heft 6, Seite(n) 667–674

Abstract: Biological age (BA) is useful for examining differences in aging rates. Nevertheless, little consensus exists regarding optimal methods for calculating BA. The aim of this study is to compare the predictive ability of five BA algorithms. The sample ... ...

Abstract	Biological age (BA) is useful for examining differences in aging rates. Nevertheless, little consensus exists regarding optimal methods for calculating BA. The aim of this study is to compare the predictive ability of five BA algorithms. The sample included 9,389 persons, aged 30-75 years, from National Health and Nutrition Examination Survey III. During the 18-year follow-up, 1,843 deaths were counted. Each BA algorithm was compared with chronological age on the basis of predictive sensitivity and strength of association with mortality. Results found that the Klemera and Doubal method was the most reliable predictor of mortality and performed significantly better than chronological age. Furthermore, when included with chronological age in a model, Klemera and Doubal method had more robust predictive ability and caused chronological age to no longer be significantly associated with mortality. Given the potential of BA to highlight heterogeneity, the Klemera and Doubal method algorithm may be useful for studying a number of questions regarding the biology of aging.
Mesh-Begriff(e)	Adult ; Aged ; Aging ; Algorithms ; Biomarkers ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Humans ; Life Expectancy/trends ; Male ; Middle Aged ; Models, Theoretical ; Mortality/trends ; Reproducibility of Results ; Sampling Studies
Chemische Substanzen	Biomarkers
Sprache	Englisch
Erscheinungsdatum	2012-12-03
Erscheinungsland	United States
Dokumenttyp	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/gls233
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk.

Brandhorst, Sebastian / Levine, Morgan E / Wei, Min / Shelehchi, Mahshid / Morgan, Todd E / Nayak, Krishna S / Dorff, Tanya / Hong, Kurt / Crimmins, Eileen M / Cohen, Pinchas / Longo, Valter D

Nature communications

2024 Band 15, Heft 1, Seite(n) 1309

Abstract: In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary ... ...

Abstract	In mice, periodic cycles of a fasting mimicking diet (FMD) protect normal cells while killing damaged cells including cancer and autoimmune cells, reduce inflammation, promote multi-system regeneration, and extend longevity. Here, we performed secondary and exploratory analysis of blood samples from a randomized clinical trial (NCT02158897) and show that 3 FMD cycles in adult study participants are associated with reduced insulin resistance and other pre-diabetes markers, lower hepatic fat (as determined by magnetic resonance imaging) and increased lymphoid to myeloid ratio: an indicator of immune system age. Based on a validated measure of biological age predictive of morbidity and mortality, 3 FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age.
Mesh-Begriff(e)	Adult ; Humans ; Animals ; Mice ; Child, Preschool ; Diet ; Fasting ; Longevity ; Liver/diagnostic imaging ; Causality
Sprache	Englisch
Erscheinungsdatum	2024-02-20
Erscheinungsland	England
Dokumenttyp	Randomized Controlled Trial ; Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45260-9
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: A Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans.

Levine, Morgan E / Crimmins, Eileen M

The journals of gerontology. Series A, Biological sciences and medical sciences

2016 Band 71, Heft 6, Seite(n) 703–712

Abstract: Human longevity and diseases are likely influenced by multiple interacting genes within a few biologically conserved pathways. Using long-lived smokers as a phenotype (n = 90)-a group whose survival may signify innate resilience-we conducted a genome- ... ...

Abstract	Human longevity and diseases are likely influenced by multiple interacting genes within a few biologically conserved pathways. Using long-lived smokers as a phenotype (n = 90)-a group whose survival may signify innate resilience-we conducted a genome-wide association study comparing them to smokers at ages 52-69 (n = 730). These results were used to conduct a functional interaction network and pathway analysis, to identify single nucleotide polymorphisms that collectively related to smokers' longevity. We identified a set of 215 single nucleotide polymorphisms (all of which had p <5×10(-3) in the genome-wide association study) that were located within genes making-up a functional interaction network. These single nucleotide polymorphisms were then used to create a weighted polygenic risk score that, using an independent validation sample of nonsmokers (N = 6,447), was found to be significantly associated with a 22% increase in the likelihood of being aged 90-99 (n = 253) and an over threefold increase in the likelihood of being a centenarian (n = 4), compared with being at ages 52-79 (n = 4,900). Additionally, the polygenic risk score was also associated with an 11% reduction in cancer prevalence over up to 18 years (odds ratio: 0.89, p = .011). Overall, using a unique phenotype and incorporating prior knowledge of biological networks, this study identified a set of single nucleotide polymorphisms that together appear to be important for human aging, stress resistance, cancer, and longevity.
Mesh-Begriff(e)	Aged ; Aged, 80 and over ; Aging/genetics ; Alleles ; Case-Control Studies ; Gene Regulatory Networks ; Genome-Wide Association Study ; Genotype ; Humans ; Longevity/genetics ; Longitudinal Studies ; Middle Aged ; Neoplasms/genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Smoking ; Stress, Physiological/genetics ; United States
Sprache	Englisch
Erscheinungsdatum	2016-06
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	1223643-3
ISSN	1758-535X ; 1079-5006
ISSN (online)	1758-535X
ISSN	1079-5006
DOI	10.1093/gerona/glv141
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Genetic associations for two biological age measures point to distinct aging phenotypes.

Kuo, Chia-Ling / Pilling, Luke C / Liu, Zuyun / Atkins, Janice L / Levine, Morgan E

Aging cell

2021 Band 20, Heft 6, Seite(n) e13376

Abstract: Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome-wide association scans of two age-adjusted biological age measures (PhenoAgeAcceleration ... ...

Abstract	Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome-wide association scans of two age-adjusted biological age measures (PhenoAgeAcceleration and BioAgeAcceleration), estimated from clinical biochemistry markers (Levine et al., 2018; Levine, 2013) in European-descent participants from UK Biobank. The strongest signals were found in the APOE gene, tagged by the two major protein-coding SNPs, PhenoAgeAccel-rs429358 (APOE e4 determinant) (p = 1.50 × 10
Mesh-Begriff(e)	Aging/genetics ; Genome-Wide Association Study/methods ; Humans ; Phenotype
Sprache	Englisch
Erscheinungsdatum	2021-05-26
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.13376
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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