scholarly journals Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans

2021 ◽  
Author(s):  
Ineke Dhondt ◽  
Clara Verschuuren ◽  
Aleksandra Zečić ◽  
Tim Loier ◽  
Bart P. Braeckman ◽  
...  
Keyword(s):  
Close Association ◽  
Visual Assessment ◽  
Muscle Architecture ◽  
Biological Age ◽  
Progressive Decline ◽  
C Elegans ◽  
Age Related ◽  
Gfp Reporter ◽  
The Relationship ◽  
Microscopy Images

Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with aging, it may represent a valuable healthspan marker. Given the commonalities with human muscle structure and facile visualization possibilities, C. elegans represents an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of aging myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens to identify modulators that mitigate age-related muscle frailty and thus improve healthspan in C. elegans.

scholarly journals Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans

2021 ◽  
Author(s):  
Ineke Dhondt ◽  
Clara Verschuuren ◽  
Aleksandra Zecic ◽  
Tim Loier ◽  
Bart Braeckman ◽  
...  
Keyword(s):  
Close Association ◽  
Muscle Architecture ◽  
Biological Age ◽  
Automated Image Analysis ◽  
Systematic Screening ◽  
C Elegans ◽  
Age Related ◽  
Gfp Reporter ◽  
Reporter Strains

Sarcopenia encompasses a progressive decline in allover muscle quantity and quality. Given its close association with aging, it may represent a valuable healthspan marker. Given the strong commonalities with human muscle structure and the facile visualization possibilities, C. elegans represents an attractive model for studying the relationship between sarcopenia and healthspan. However, classical assessment relies on visual scoring of muscle architecture, which is subjective and inaccurate. To resolve this, we have developed an automated image analysis pipeline for the detailed quantification and classification of muscle integrity in confocal microscopy images from a cohort of aging myosin::GFP reporter strains. We then extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed us to establish a general linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted RNAi-mediated knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and will be of use for systematic screening for pharmacological or genetic modulators that mitigate age-related muscle frailty and thus improve healthspan in C. elegans.

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 Electrophysiological Measures of Aging Pharynx Function in C. elegans Reveal Enhanced Organ Functionality in Older, Long-lived Mutants

2017 ◽  
Vol 74 (8) ◽  
pp. 1173-1179 ◽  
Author(s):  
Joshua Coulter Russell ◽  
Nikolay Burnaevskiy ◽  
Bridget Ma ◽  
Miguel Arenas Mailig ◽  
Franklin Faust ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Life Span ◽  
Insulin Signaling ◽  
Model System ◽  
Wild Type ◽  
Organ Function ◽  
C Elegans ◽  
Age Related ◽  
The Relationship

Abstract The function of the pharynx, an organ in the model system Caenorhabditis elegans, has been correlated with life span and motility (another measure of health) since 1980. In this study, in order to further understand the relationship between organ function and life span, we measured the age-related decline of the pharynx using an electrophysiological approach. We measured and analyzed electropharyngeograms (EPG) of wild type animals, short-lived hsf-1 mutants, and long-lived animals with genetically decreased insulin signaling or increased heat shock pathway signaling; we recorded a total of 2,478 EPGs from 1,374 individuals. As expected, the long-lived daf-2(e1370) and hsf-1OE(uthIs235) animals maintained pharynx function relatively closer to the youthful state during aging, whereas the hsf-1(sy441) and wild type animals’ pharynx function deviated significantly further from the youthful state at advanced age. Measures of the amount of variation in organ function can act as biomarkers of youthful physiology as well. Intriguingly, the long-lived animals had greater variation in the duration of pharynx contraction at older ages.

scholarly journals Protein Posttranslational Modifications: Roles in Aging and Age-Related Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Ana L. Santos ◽  
Ariel B. Lindner
Keyword(s):  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Molecular Processes ◽  
Progressive Decline ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Protein Posttranslational Modifications ◽  
Aging Models ◽  
The Relationship

Aging is characterized by the progressive decline of biochemical and physiological function in an individual. Consequently, aging is a major risk factor for diseases like cancer, obesity, and type 2 diabetes. The cellular and molecular mechanisms of aging are not well understood, nor is the relationship between aging and the onset of diseases. One of the hallmarks of aging is a decrease in cellular proteome homeostasis, allowing abnormal proteins to accumulate. This phenomenon is observed in both eukaryotes and prokaryotes, suggesting that the underlying molecular processes are evolutionarily conserved. Similar protein aggregation occurs in the pathogenesis of diseases like Alzheimer’s and Parkinson’s. Further, protein posttranslational modifications (PTMs), either spontaneous or physiological/pathological, are emerging as important markers of aging and aging-related diseases, though clear causality has not yet been firmly established. This review presents an overview of the interplay of PTMs in aging-associated molecular processes in eukaryotic aging models. Understanding PTM roles in aging could facilitate targeted therapies or interventions for age-related diseases. In addition, the study of PTMs in prokaryotes is highlighted, revealing the potential of simple prokaryotic models to uncover complex aging-associated molecular processes in the emerging field of microbiogerontology.

scholarly journals Statistical image processing quantifies the changes in cytoplasmic texture associated with aging in Caenorhabditis elegans oocytes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Momoko Imakubo ◽  
Jun Takayama ◽  
Hatsumi Okada ◽  
Shuichi Onami
Keyword(s):  
Image Processing ◽  
Caenorhabditis Elegans ◽  
Texture Feature ◽  
Oocyte Quality ◽  
Differential Interference Contrast Microscopy ◽  
C Elegans ◽  
Age Related ◽  
The Difference ◽  
Occurrence Matrix ◽  
Microscopy Images

AbstractBackgroundOocyte quality decreases with aging, thereby increasing errors in fertilization, chromosome segregation, and embryonic cleavage. Oocyte appearance also changes with aging, suggesting a functional relationship between oocyte quality and appearance. However, no methods are available to objectively quantify age-associated changes in oocyte appearance.ResultsWe show that statistical image processing of Nomarski differential interference contrast microscopy images can be used to quantify age-associated changes in oocyte appearance in the nematodeCaenorhabditis elegans. Max–min value (mean difference between the maximum and minimum intensities within each moving window) quantitatively characterized the difference in oocyte cytoplasmic texture between 1- and 3-day-old adults (Day 1 and Day 3 oocytes, respectively). With an appropriate parameter set, the gray level co-occurrence matrix (GLCM)-based texture featureCorrelation(COR) more sensitively characterized this difference than the Max–min Value. Manipulating the smoothness of and/or adding irregular structures to the cytoplasmic texture of Day 1 oocyte images reproduced the difference in Max–min Value but not in COR between Day 1 and Day 3 oocytes. Increasing the size of granules in synthetic images recapitulated the age-associated changes in COR. Manual measurements validated that the cytoplasmic granules in oocytes become larger with aging.ConclusionsThe Max–min value and COR objectively quantify age-related changes inC. elegansoocyte in Nomarski DIC microscopy images. Our methods provide new opportunities for understanding the mechanism underlying oocyte aging.

scholarly journals Senotherapeutic peptide reduces skin biological age and improves skin health markers

2020 ◽  
Author(s):  
Alessandra Zonari ◽  
Lear E. Brace ◽  
Kallie Z. Al-Katib ◽  
William F. Porto ◽  
Daniel Foyt ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Ultraviolet B ◽  
Biological Age ◽  
Chronological Aging ◽  
C Elegans ◽  
Age Related ◽  
Etoposide Treatment ◽  
Screening Platform

AbstractSkin aging has been primarily related to aesthetics and beauty. Therefore, interventions have focused on reestablishing skin appearance, but not necessarily skin health, function, and resilience. Recently, cellular senescence was shown to play a role in age-related skin function deterioration and influence organismal health and, potentially, longevity. In the present study, a two-step screening was performed to identify peptides capable of reducing cellular senescence in human dermal fibroblasts (HDF) from Hutchinson-Gilford Progeria (HGPS) patients. From the top four peptides of the first round of screening, we built a 764-peptide library using amino acid scanning, of which the second screen led to the identification of peptide 14. Peptide 14 effectively decreased HDF senescence induced by HGPS, chronological aging, ultraviolet-B radiation, and etoposide treatment, without inducing significant cell death, and likely by modulating longevity and senescence pathways. We further validated the effectiveness of peptide 14 using human skin equivalents and skin biopsies, where peptide 14 promoted skin health and reduced senescent cell markers, as well as the biological age of samples, according to the Skin-Specific DNA methylation clock, MolClock. Topical application of peptide 14 outperformed Retinol treatment, the current gold-standard in “anti-aging” skin care. Finally, we determined that peptide 14 is safe for long-term applications and also significantly extends both the lifespan and healthspan of C. elegans worms tested in two independent testings. This highlights the potential for geroprotective applications of the senotherapeutic compounds identified using our screening platform beyond the skin.

scholarly journals Forward genetic screen forCaenorhabditis elegansmutants with a shortened locomotor healthspan

2018 ◽  
Author(s):  
Kazuto Kawamura ◽  
Ichiro N. Maruyama
Keyword(s):  
Progressive Decline ◽  
Forward Genetic Screen ◽  
C Elegans ◽  
Short Lifespan ◽  
Elongator Complex ◽  
Age Related ◽  
Mutant Strains ◽  
Complex Protein ◽  
Locomotor Impairment ◽  
Locomotor Deficits

AbstractTwo people with the same lifespan do not necessarily have the same healthspan. One person may retain locomotor and cognitive functions until the end of life, while another person may lose them during adulthood. Unbiased searches for genes that are required to maintain locomotor capacities during adulthood may uncover key regulators of locomotor healthspan. Here, we take advantage of the relatively short lifespan of the nematodeCaenorhabditis elegansand develop a novel screening procedure to collect mutants with locomotor deficits that become apparent in adulthood. After ethyl methanesulfonate mutagenesis, we isolated fiveC. elegansmutant strains that progressively lose adult locomotor activity. In one of the mutant strains, a nonsense mutation in Elongator Complex Protein Component 2 (elpc-2)causes a progressive decline in locomotor function. Mutants and mutations identified in the present screen may provide insights into mechanisms of age-related locomotor impairment and the maintenance of locomotor healthspan.

scholarly journals Statistical image processing quantifies the changes in cytoplasmic texture associated with aging in Caenorhabditis elegans oocytes

2020 ◽  
Author(s):  
Momoko Imakubo ◽  
Jun Takayama ◽  
Hatsumi Okada ◽  
Shuichi Onami
Keyword(s):  
Image Processing ◽  
Caenorhabditis Elegans ◽  
Texture Feature ◽  
Oocyte Quality ◽  
Differential Interference Contrast Microscopy ◽  
C Elegans ◽  
Age Related ◽  
The Difference ◽  
Occurrence Matrix ◽  
Microscopy Images

AbstractBackgroundOocyte quality decreases with aging, thereby increasing errors in fertilization, chromosome segregation, and embryonic cleavage. Oocyte appearance also changes with aging, suggesting a functional relationship between oocyte quality and appearance. However, no methods are available to objectively quantify age-associated changes in oocyte appearance.ResultsWe show that statistical image processing of Nomarski differential interference contrast microscopy images can be used to quantify age-associated changes in Caenorhabditis elegans oocyte appearance. Max-min Value (mean difference between the maximum and minimum intensities within each moving window) quantitatively characterized the difference in oocyte cytoplasmic texture between 1- and 3-day-old adults (Day 1 and Day 3 oocytes, respectively). With an appropriate parameter set, the gray level co-occurrence matrix (GLCM)-based texture feature Correlation (COR) more sensitively characterized this difference than the Max-min Value. Manipulating the smoothness of and/or adding irregular structures to the cytoplasmic texture of Day 1 oocyte images reproduced the difference in Max-min Value but not in COR between Day 1 and Day 3 oocytes. Increasing the size of granules in synthetic images recapitulated the age-associated changes in COR. Manual measurements validated that the cytoplasmic granules in oocytes become larger with aging.ConclusionsThe Max-min Value and COR objectively quantify age-related changes in C. elegans oocyte in Nomarski DIC microscopy images. Our methods provide new opportunities for understanding the mechanism underlying oocyte aging.

scholarly journals Class I histone deacetylase HDA-3 is required for full maintenance of locomotor ability in Caenorhabditis elegans

2019 ◽  
Author(s):  
Kazuto Kawamura ◽  
Ichiro N. Maruyama
Keyword(s):  
Histone Deacetylase ◽  
Genetic Factors ◽  
Class I ◽  
Causative Mutation ◽  
Progressive Decline ◽  
C Elegans ◽  
Age Related ◽  
Genetic And Environmental Factors ◽  
Chromosome Ii ◽  
Locomotor Ability

ABSTRACTLocomotor ability declines with old age. A person’s capacity to maintain locomotor ability depends on genetic and environmental factors. Currently, the specific genetic factors that work to maintain locomotor ability are not well understood. Here we report the involvement of hda-3, encoding a class I histone deacetylase, as a specific genetic factor that contributes to the maintenance of locomotor ability in C. elegans. From a forward genetic approach, we identified a missense mutation in HDA-3 as the causative mutation for progressive decline in locomotor ability in one of the isolated strains. From transcriptome analysis, we found downregulated expression of two clusters of genes on Chromosome II and IV in this strain. Genes carrying CUB-like domains and genes carrying BATH domains were found on Chromosome II and IV, respectively. Knockdown of CUB-like genes, K08D8.5 and dod-17, and BATH genes, bath-1, bath-21 and bath-24 led to a progressive decline in locomotor ability. Our study identifies specific genetic factors that work to maintain locomotor ability and reveals potential targets for delaying age-related locomotor decline.

Cognitive Factors Mediate the Relation Between Age and Flight Path Maintenance in General Aviation

2016 ◽  
Vol 6 (2) ◽  
pp. 81-90 ◽  
Author(s):  
Kathleen Van Benthem ◽  
Chris M. Herdman
Keyword(s):  
Cognitive Functioning ◽  
Flight Path ◽  
General Aviation ◽  
Cognitive Factors ◽  
Pilot Performance ◽  
Pilot Error ◽  
Age Related ◽  
And Performance ◽  
Relationship Of ◽  
The Relationship

Abstract. Identifying pilot attributes associated with risk is important, especially in general aviation where pilot error is implicated in most accidents. This research examined the relationship of pilot age, expertise, and cognitive functioning to deviations from an ideal circuit trajectory. In all, 54 pilots, of varying age, flew a Cessna 172 simulator. Cognitive measures were obtained using the CogScreen-AE ( Kay, 1995 ). Older age and lower levels of expertise and cognitive functioning were associated with significantly greater flight path deviations. The relationship between age and performance was fully mediated by a cluster of cognitive factors: speed and working memory, visual attention, and cognitive flexibility. These findings add to the literature showing that age-related changes in cognition may impact pilot performance.

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