scholarly journals Biological Age Prediction From Wearable Device Movement Data Identifies Nutritional and Pharmacological Interventions for Healthy Aging

2021 ◽  
Vol 2 ◽  
Author(s):  
Rebecca L. McIntyre ◽  
Mizanur Rahman ◽  
Siva A. Vanapalli ◽  
Riekelt H. Houtkooper ◽  
Georges E. Janssens
Keyword(s):  
Healthy Aging ◽  
Machine Learning Algorithms ◽  
Biological Age ◽  
Wearable Device ◽  
Biological Aging ◽  
Accelerometer Data ◽  
Pharmacological Interventions ◽  
C Elegans ◽  
Movement Data ◽  
Age Related

Intervening in aging processes is hypothesized to extend healthy years of life and treat age-related disease, thereby providing great benefit to society. However, the ability to measure the biological aging process in individuals, which is necessary to test for efficacy of these interventions, remains largely inaccessible to the general public. Here we used NHANES physical activity accelerometer data from a wearable device and machine-learning algorithms to derive biological age predictions for individuals based on their movement patterns. We found that accelerated biological aging from our “MoveAge” predictor is associated with higher all-cause mortality. We further searched for nutritional or pharmacological compounds that associate with decelerated aging according to our model. A number of nutritional components peak in their association to decelerated aging later in life, including fiber, magnesium, and vitamin E. We additionally identified one FDA-approved drug associated with decelerated biological aging: the alpha-blocker doxazosin. We show that doxazosin extends healthspan and lifespan in C. elegans. Our work demonstrates how a biological aging score based on relative mobility can be accessible to the wider public and can potentially be used to identify and determine efficacy of geroprotective interventions.

scholarly journals COMPARABILITY OF BIOLOGICAL AGING MEASURES IN THE NATIONAL HEALTH AND NUTRITION EXAMINATION STUDY, 1999-2002

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S479-S479
Author(s):  
Waylon J Hastings ◽  
Daniel Belsky ◽  
Idan Shalev
Keyword(s):  
Risk Factors ◽  
Telomere Length ◽  
Cellular Level ◽  
Biological Age ◽  
Effect Sizes ◽  
Chronological Age ◽  
Biological Aging ◽  
Patient Level ◽  
Age Related ◽  
Level Information

Abstract Biological processes of aging are thought to be modifiable causes of many chronic diseases. Measures of biological aging could provide sensitive endpoints for studies of risk factors hypothesized to shorten healthy lifespan and/or interventions that extend it. However, uncertainty remains about how to measure biological aging and if proposed measures assess the same thing. We tested four proposed measures of biological aging with available data from NHANES 1999-2002: Klemera-Doubal method (KDM) Biological Age, homeostatic dysregulation, Levine Method (LM) Biological Age, and leukocyte telomere length. All measures of biological aging were correlated with chronological age. KDM Biological Age, homeostatic dysregulation, and LM Biological Age were all significantly associated with each other, but were each not associated with telomere length. NHANES participants with older biological ages performed worse on tests of physical, cognitive, perceptual, and subjective functions known to decline with advancing chronological age and thought to mediate age-related disability. Further, NHANES participants with higher levels of exposure to life-course risk factors were measured as having older biological ages. In both sets of analyses, effect-sizes tended to be larger for KDM Biological Age, homeostatic dysregulation, and LM Biological Age as compared to telomere length. Composite measures combining cellular- and patient-level information tended to have the largest effect-sizes. The cellular-level aging biomarker telomere length may measure different aspects of the aging process relative to the patient-level physiological measures. Studies aiming to test if risk factors accelerate aging or if interventions may slow aging should not treat proposed measures of biological aging as interchangeable.

scholarly journals Exploring Epigenetic Age in Response to Intensive Relaxing Training: A Pilot Study to Slow Down Biological Age

2019 ◽  
Vol 16 (17) ◽  
pp. 3074 ◽  
Author(s):  
Pavanello ◽  
Campisi ◽  
Tona ◽  
Lin ◽  
Iliceto
Keyword(s):  
Myocardial Infarction ◽  
Age Estimation ◽  
Healthy Subjects ◽  
Molecular Mechanisms ◽  
Biological Age ◽  
Chronological Age ◽  
Biological Aging ◽  
Epigenetic Clock ◽  
Age Related ◽  
Epigenetic Age

DNA methylation (DNAm) is an emerging estimator of biological aging, i.e., the often-defined “epigenetic clock”, with a unique accuracy for chronological age estimation (DNAmAge). In this pilot longitudinal study, we examine the hypothesis that intensive relaxing training of 60 days in patients after myocardial infarction and in healthy subjects may influence leucocyte DNAmAge by turning back the epigenetic clock. Moreover, we compare DNAmAge with another mechanism of biological age, leucocyte telomere length (LTL) and telomerase. DNAmAge is reduced after training in healthy subjects (p = 0.053), but not in patients. LTL is preserved after intervention in healthy subjects, while it continues to decrease in patients (p = 0.051). The conventional negative correlation between LTL and chronological age becomes positive after training in both patients (p < 0.01) and healthy subjects (p < 0.05). In our subjects, DNAmAge is not associated with LTL. Our findings would suggest that intensive relaxing practices influence different aging molecular mechanisms, i.e., DNAmAge and LTL, with a rejuvenating effect. Our study reveals that DNAmAge may represent an accurate tool to measure the effectiveness of lifestyle-based interventions in the prevention of age-related diseases.

scholarly journals COVID-19 severity is predicted by earlier evidence of accelerated aging

2020 ◽  
Author(s):  
Chia-Ling Kuo ◽  
Luke C. Pilling ◽  
Janice L Atkins ◽  
Jane AH Masoli ◽  
João Delgado ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Accelerated Aging ◽  
Biological Age ◽  
Chronological Age ◽  
Biological Aging ◽  
Severe Illness ◽  
Mortality Data ◽  
Age Related ◽  
Underlying Mechanisms ◽  
The Uk

AbstractWith no known treatments or vaccine, COVID-19 presents a major threat, particularly to older adults, who account for the majority of severe illness and deaths. The age-related susceptibility is partly explained by increased comorbidities including dementia and type II diabetes [1]. While it is unclear why these diseases predispose risk, we hypothesize that increased biological age, rather than chronological age, may be driving disease-related trends in COVID-19 severity with age. To test this hypothesis, we applied our previously validated biological age measure (PhenoAge) [2] composed of chronological age and nine clinical chemistry biomarkers to data of 347,751 participants from a large community cohort in the United Kingdom (UK Biobank), recruited between 2006 and 2010. Other data included disease diagnoses (to 2017), mortality data (to 2020), and the UK national COVID-19 test results (to May 31, 2020) [3]. Accelerated aging 10-14 years prior to the start of the COVID-19 pandemic was associated with test positivity (OR=1.15 per 5-year acceleration, 95% CI: 1.08 to 1.21, p=3.2×10−6) and all-cause mortality with test-confirmed COVID-19 (OR=1.25, per 5-year acceleration, 95% CI: 1.09 to 1.44, p=0.002) after adjustment for demographics including current chronological age and pre-existing diseases or conditions. The corresponding areas under the curves were 0.669 and 0.803, respectively. Biological aging, as captured by PhenoAge, is a better predictor of COVID-19 severity than chronological age, and may inform risk stratification initiatives, while also elucidating possible underlying mechanisms, particularly those related to inflammaging.

Individual DNA Methylation Profile is Correlated with Age and can be Targeted to Modulate Healthy Aging and Longevity

2019 ◽  
Vol 25 (39) ◽  
pp. 4139-4149 ◽  
Author(s):  
Francesco Guarasci ◽  
Patrizia D'Aquila ◽  
Alberto Montesanto ◽  
Andrea Corsonello ◽  
Dina Bellizzi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Aging Process ◽  
Healthy Aging ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Biological Aging ◽  
Biomarkers Of Aging ◽  
Age Related

: Patterns of DNA methylation, the best characterized epigenetic modification, are modulated by aging. In humans, different studies at both site-specific and genome-wide levels have reported that modifications of DNA methylation are associated with the chronological aging process but also with the quality of aging (or biological aging), providing new perspectives for establishing powerful biomarkers of aging. : In this article, the role of DNA methylation in aging and longevity has been reviewed by analysing literature data about DNA methylation variations occurring during the lifetime in response to environmental factors and genetic background, and their association with the aging process and, in particular, with the quality of aging. Special attention has been devoted to the relationship between nuclear DNA methylation patterns, mitochondrial DNA epigenetic modifications, and longevity. Mitochondrial DNA has recently been reported to modulate global DNA methylation levels of the nuclear genome during the lifetime, and, in spite of the previous belief, it has been found to be the target of methylation modifications. : Analysis of DNA methylation profiles across lifetime shows that a remodeling of the methylome occurs with age and/or with age-related decline. Thus, it can be an excellent biomarker of aging and of the individual decline and frailty status. The knowledge about the mechanisms underlying these modifications is crucial since it might allow the opportunity for targeted treatment to modulate the rate of aging and longevity.

Successful Aging

2017 ◽  
Author(s):  
Dilip Jeste ◽  
Jeanne Maglione
Keyword(s):  
Older Adults ◽  
Cognitive Aging ◽  
Successful Aging ◽  
Healthy Aging ◽  
Biological Aging ◽  
Medical Illness ◽  
Key Words Aging ◽  
Age Related ◽  
Different Populations ◽  
Multiple Domains

The number of older adults in our society is increasing rapidly. Aging is complex and may occur at varying rates across multiple domains, including biological aging, cognitive aging, and emotional aging. Age-related medical conditions are now among the leading causes of morbidity and mortality among older adults, making healthy aging a major public health priority. Successful aging encompasses more than longevity, medical health, or freedom from disability. It can be viewed as a multidimensional construct including minimization of disability and medical illness combined with maximization of physical, cognitive, emotional, and social functioning. We review the current literature regarding successful aging. We also discuss strategies to improve the likelihood of successful aging and several key advances, such as definitions of successful aging in different populations, neuroplasticity of aging, wisdom as an empirical construct, the concept of a good (or successful) death, and the development of age-friendly communities.  This review contains 3 figures, 5 tables, and 53 references. Key words: aging, elderly, older adult, successful aging, successful aging interventions

scholarly journals Indoles from commensal bacteria extend healthspan

2017 ◽  
Vol 114 (36) ◽  
pp. E7506-E7515 ◽  
Author(s):  
Robert Sonowal ◽  
Alyson Swimm ◽  
Anusmita Sahoo ◽  
Liping Luo ◽  
Yohei Matsunaga ◽  
...  
Keyword(s):  
Small Molecules ◽  
Healthy Aging ◽  
Commensal Bacteria ◽  
Molecular Pathways ◽  
Genetic Pathways ◽  
C Elegans ◽  
Commensal Microbiota ◽  
Aryl Hydrocarbon ◽  
Age Related ◽  
Animal Remains

Multiple studies have identified conserved genetic pathways and small molecules associated with extension of lifespan in diverse organisms. However, extending lifespan does not result in concomitant extension in healthspan, defined as the proportion of time that an animal remains healthy and free of age-related infirmities. Rather, mutations that extend lifespan often reduce healthspan and increase frailty. The question arises as to whether factors or mechanisms exist that uncouple these processes and extend healthspan and reduce frailty independent of lifespan. We show that indoles from commensal microbiota extend healthspan of diverse organisms, including Caenorhabditis elegans, Drosophila melanogaster, and mice, but have a negligible effect on maximal lifespan. Effects of indoles on healthspan in worms and flies depend upon the aryl hydrocarbon receptor (AHR), a conserved detector of xenobiotic small molecules. In C. elegans, indole induces a gene expression profile in aged animals reminiscent of that seen in the young, but which is distinct from that associated with normal aging. Moreover, in older animals, indole induces genes associated with oogenesis and, accordingly, extends fecundity and reproductive span. Together, these data suggest that small molecules related to indole and derived from commensal microbiota act in diverse phyla via conserved molecular pathways to promote healthy aging. These data raise the possibility of developing therapeutics based on microbiota-derived indole or its derivatives to extend healthspan and reduce frailty in humans.

scholarly journals IN VIVO ANALYSIS OF REPORTER ALLELES REVEALS INCREASED VARIABILITY OF GENE EXPRESSION IN CELLS AND ANIMALS WITH AGE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S101-S101
Author(s):  
Nikolay Burnaevskiy ◽  
Bryan Sands ◽  
Soo Yun ◽  
Alexander Mendenhall
Keyword(s):  
Gene Expression ◽  
Analytical Framework ◽  
Biological Aging ◽  
Early Event ◽  
Quantitative Microscopy ◽  
C Elegans ◽  
Age Related ◽  
Stochastic Events ◽  
Noise In Gene Expression

Abstract As a major risk factor for a multitude of chronic diseases aging is being increasingly recognized as a necessary therapeutic target for preventive medicine. Yet, despite tremendous progress in our understanding of the genetic determinants of longevity, proximal causes of aging remain incompletely understood. In part, this may be due to a plethora of factors, such as various types of stochastic macromolecular damage that affect individual cells and individual animals. Indeed, recent studies point to an increase of cell-to-cell variability in gene expression within old tissues, supporting the idea that stochastic events contribute to the aging process. Therefore, more single-cell focused studies are needed for a complete understanding of biological aging. Here, we utilized quantitative microscopy for analysis of gene expression in individual aging cells, in vivo in C. elegans. Using transcriptional reporters, fluorescently tagged proteins and a quantitative analytical framework adapted from yeast, we have found that young C. elegans exhibit very little stochastic or signaling noise in gene expression. However, using quantitative microscopy, we directly observed dysregulation of gene expression with age in vivo. Specifically, the stoichiometric ratios of proteins that are tightly regulated among the youthful populace start deviating in a cell autonomous fashion. Importantly, we find that an increase of gene expression variation is a relatively early event in the aging of C. elegans, readily observed before median lifespan. Hence, we suggest that incoherent cell-to-cell variation in gene expression arising with age can be an immediate causal factor for age-related loss of robust tissue function.

scholarly journals The INSPIRE Bio-resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort)

2020 ◽  
pp. 1-11 ◽  
Author(s):  
S. Guyonnet ◽  
Y. Rolland ◽  
C. Takeda ◽  
P.-J. Ousset ◽  
I. Ader ◽  
...  
Keyword(s):  
Health Care ◽  
Translational Research ◽  
Healthy Aging ◽  
Care Pathway ◽  
Integrative Approach ◽  
Biological Aging ◽  
Imaging Data ◽  
Aging Research ◽  
Age Related

Background: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. Objectives: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. Methods: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. Expected Results: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.

scholarly journals SENESCENCE SECRETOME: BIOMARKERS OF BIOLOGICAL AGING AND POSTOPERATIVE OUTCOMES

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S98-S98
Author(s):  
Marissa Schafer ◽  
Xu Zhang ◽  
Amanika Kumar ◽  
Thomas White ◽  
Elizabeth Atkinson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Aortic Stenosis ◽  
Clinical Decision Making ◽  
Adverse Outcomes ◽  
Biological Age ◽  
Postoperative Outcomes ◽  
Gradient Boosting ◽  
Cancer Case ◽  
Biological Aging ◽  
Age Related

Abstract Senescent cells drive age-related tissue dysfunction through their potent secretome, termed the senescence associated secretory phenotype (SASP). Circulating concentrations of SASP factors may reflect biological age and serve as clinically useful biomarkers of surgical risk and ultimately, surrogate endpoints in clinical trials. However, they remain largely uncharacterized. We tested associations between circulating concentrations of SASP proteins and biological age, as determined by the accumulation of age-related health deficits, and/or postoperative outcomes in a sample of residents in Olmstead County, MN, age 60-90 years (n = 115) and cohorts of older adults undergoing surgery for severe aortic stenosis (prospective; n = 97) or ovarian cancer (case-control; n = 36). Circulating concentrations of SASP factors were associated with biological age and adverse postoperative outcomes, including risk of any adverse event or rehospitalization within the year following surgery (aortic stenosis group) or admission to an intensive care unit within 30 days of hospital discharge (ovarian cancer group). Gradient boosting machine modeling revealed a panel of SASP factors that predicted adverse outcomes across both surgical groups better than biological age or chronological age and sex. This suggests that the circulating SASP is a robust indicator of age-related health status and may help guide clinical decision making. Furthermore, circulating SASP factors may be harnessed as a readily quantifiable biomarkers in senescence-targeting interventional human studies.

scholarly journals Phenotypic Screening in C. elegans as a Tool for the Discovery of New Geroprotective Drugs

2020 ◽  
Vol 13 (8) ◽  
pp. 164 ◽  
Author(s):  
Sven Bulterijs ◽  
Bart P. Braeckman
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Aging Process ◽  
Population Aging ◽  
Model Organisms ◽  
Pharmacological Interventions ◽  
C Elegans ◽  
System A ◽  
Age Related ◽  
Screening Strategies

Population aging is one of the largest challenges of the 21st century. As more people live to advanced ages, the prevalence of age-related diseases and disabilities will increase placing an ever larger burden on our healthcare system. A potential solution to this conundrum is to develop treatments that prevent, delay or reduce the severity of age-related diseases by decreasing the rate of the aging process. This ambition has been accomplished in model organisms through dietary, genetic and pharmacological interventions. The pharmacological approaches hold the greatest opportunity for successful translation to the clinic. The discovery of such pharmacological interventions in aging requires high-throughput screening strategies. However, the majority of screens performed for geroprotective drugs in C. elegans so far are rather low throughput. Therefore, the development of high-throughput screening strategies is of utmost importance.

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