Limits...
Quantitative image analysis reveals distinct structural transitions during aging in Caenorhabditis elegans tissues.

Johnston J, Iser WB, Chow DK, Goldberg IG, Wolkow CA - PLoS ONE (2008)

Bottom Line: Such approaches are inadequate for the complex changes associated with aging.The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate.This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, NIA Intramural Research Program, National Institutes of Health, Baltimore, Maryland, United States of America.

ABSTRACT
Aging is associated with functional and structural declines in many body systems, even in the absence of underlying disease. In particular, skeletal muscles experience severe declines during aging, a phenomenon termed sarcopenia. Despite the high incidence and severity of sarcopenia, little is known about contributing factors and development. Many studies focus on functional aspects of aging-related tissue decline, while structural details remain understudied. Traditional approaches for quantifying structural changes have assessed individual markers at discrete intervals. Such approaches are inadequate for the complex changes associated with aging. An alternative is to consider changes in overall morphology rather than in specific markers. We have used this approach to quantitatively track tissue architecture during adulthood and aging in the C. elegans pharynx, the neuromuscular feeding organ. Using pattern recognition to analyze aged-grouped pharynx images, we identified discrete step-wise transitions between distinct morphologies. The morphology state transitions were maintained in mutants with pharynx neurotransmission defects, although the pace of the transitions was altered. Longitudinal measurements of pharynx function identified a predictive relationship between mid-life pharynx morphology and function at later ages. These studies demonstrate for the first time that adult tissues undergo distinct structural transitions reflecting postdevelopmental events. The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate. This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers.

Show MeSH

Related in: MedlinePlus

The aging model built on pharynx images from adult days 0–12 properly ordered the images by age.(A) Pair-wise image distances used to generate the dendrogram were calculated in the class-distance subspace, where each dimension is the distance from a test image to the centroid of an age-class. (B) Relationships between adult pharynx images from early to late life as determined by the aging model. Circles at branch end-points represent individual pharynx images, with color indicating the animal's age at the time of imaging. Branch lengths represent pair-wise distances between images, and branch colors represent the ages of proximal images. This diagram shows that images could be classified into categories corresponding to early adulthood (day 0, red), middle adulthood (days 2 and 4, orange) and late adulthood (day 6 and older, green and cyan). For training, 85 images from fem-1(hc17) adults aged day 0 to 12 were used for each class. The dendrogram was constructed from 20 test images selected at random from each class.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2483734&req=5

pone-0002821-g002: The aging model built on pharynx images from adult days 0–12 properly ordered the images by age.(A) Pair-wise image distances used to generate the dendrogram were calculated in the class-distance subspace, where each dimension is the distance from a test image to the centroid of an age-class. (B) Relationships between adult pharynx images from early to late life as determined by the aging model. Circles at branch end-points represent individual pharynx images, with color indicating the animal's age at the time of imaging. Branch lengths represent pair-wise distances between images, and branch colors represent the ages of proximal images. This diagram shows that images could be classified into categories corresponding to early adulthood (day 0, red), middle adulthood (days 2 and 4, orange) and late adulthood (day 6 and older, green and cyan). For training, 85 images from fem-1(hc17) adults aged day 0 to 12 were used for each class. The dendrogram was constructed from 20 test images selected at random from each class.

Mentions: To compute similarities between test images, the distances between each image and each of the class centroids were used to form another subspace with a dimensionality equal to the number of classes (Fig. 2A). The positions of individual images within this class-distance subspace were plotted as individual points. The pair-wise distances between points, indicating similarity between images, were used to construct a dendrogram (Fig. 2B). During training, the model did not receive any information on the age-order of the training images. If the model were able to detect an age progression, then test images in the dendrogram would be ordered by their chronological age rather than clustered into unordered age groups. The dendrogram was correctly self-ordered with respect to age in many cases, particularly for the early age groups (days 0–4). In addition, this dendrogram portrayed a tight progression of morphologies during very early adulthood (days 0–2) (Fig. 2B, red & orange icons). This progression could reflect pharynx growth as part of the overall increase in body size during this time [13]. Images from animals older than day 4 were more closely spaced in the dendrogram than very young adults, suggesting greater image similarity after day 4. Later ages (days 10,12) showed an even greater degree of self-similarity, resulting in closer spacing in this visualization. Overall, this method defined a progression of image features that correlated with age, such that images from middle-aged animals (i.e. day 4, orange) were more similar overall to images from younger animals (day 0, red) than old adults (day 10, blue) and vice versa. It is also evident from this visualization that progressive changes in image features occur during this period of adulthood, thus this model can be used to assign a continuous age score for each individual pharynx image.


Quantitative image analysis reveals distinct structural transitions during aging in Caenorhabditis elegans tissues.

Johnston J, Iser WB, Chow DK, Goldberg IG, Wolkow CA - PLoS ONE (2008)

The aging model built on pharynx images from adult days 0–12 properly ordered the images by age.(A) Pair-wise image distances used to generate the dendrogram were calculated in the class-distance subspace, where each dimension is the distance from a test image to the centroid of an age-class. (B) Relationships between adult pharynx images from early to late life as determined by the aging model. Circles at branch end-points represent individual pharynx images, with color indicating the animal's age at the time of imaging. Branch lengths represent pair-wise distances between images, and branch colors represent the ages of proximal images. This diagram shows that images could be classified into categories corresponding to early adulthood (day 0, red), middle adulthood (days 2 and 4, orange) and late adulthood (day 6 and older, green and cyan). For training, 85 images from fem-1(hc17) adults aged day 0 to 12 were used for each class. The dendrogram was constructed from 20 test images selected at random from each class.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2483734&req=5

pone-0002821-g002: The aging model built on pharynx images from adult days 0–12 properly ordered the images by age.(A) Pair-wise image distances used to generate the dendrogram were calculated in the class-distance subspace, where each dimension is the distance from a test image to the centroid of an age-class. (B) Relationships between adult pharynx images from early to late life as determined by the aging model. Circles at branch end-points represent individual pharynx images, with color indicating the animal's age at the time of imaging. Branch lengths represent pair-wise distances between images, and branch colors represent the ages of proximal images. This diagram shows that images could be classified into categories corresponding to early adulthood (day 0, red), middle adulthood (days 2 and 4, orange) and late adulthood (day 6 and older, green and cyan). For training, 85 images from fem-1(hc17) adults aged day 0 to 12 were used for each class. The dendrogram was constructed from 20 test images selected at random from each class.
Mentions: To compute similarities between test images, the distances between each image and each of the class centroids were used to form another subspace with a dimensionality equal to the number of classes (Fig. 2A). The positions of individual images within this class-distance subspace were plotted as individual points. The pair-wise distances between points, indicating similarity between images, were used to construct a dendrogram (Fig. 2B). During training, the model did not receive any information on the age-order of the training images. If the model were able to detect an age progression, then test images in the dendrogram would be ordered by their chronological age rather than clustered into unordered age groups. The dendrogram was correctly self-ordered with respect to age in many cases, particularly for the early age groups (days 0–4). In addition, this dendrogram portrayed a tight progression of morphologies during very early adulthood (days 0–2) (Fig. 2B, red & orange icons). This progression could reflect pharynx growth as part of the overall increase in body size during this time [13]. Images from animals older than day 4 were more closely spaced in the dendrogram than very young adults, suggesting greater image similarity after day 4. Later ages (days 10,12) showed an even greater degree of self-similarity, resulting in closer spacing in this visualization. Overall, this method defined a progression of image features that correlated with age, such that images from middle-aged animals (i.e. day 4, orange) were more similar overall to images from younger animals (day 0, red) than old adults (day 10, blue) and vice versa. It is also evident from this visualization that progressive changes in image features occur during this period of adulthood, thus this model can be used to assign a continuous age score for each individual pharynx image.

Bottom Line: Such approaches are inadequate for the complex changes associated with aging.The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate.This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Genetics, NIA Intramural Research Program, National Institutes of Health, Baltimore, Maryland, United States of America.

ABSTRACT
Aging is associated with functional and structural declines in many body systems, even in the absence of underlying disease. In particular, skeletal muscles experience severe declines during aging, a phenomenon termed sarcopenia. Despite the high incidence and severity of sarcopenia, little is known about contributing factors and development. Many studies focus on functional aspects of aging-related tissue decline, while structural details remain understudied. Traditional approaches for quantifying structural changes have assessed individual markers at discrete intervals. Such approaches are inadequate for the complex changes associated with aging. An alternative is to consider changes in overall morphology rather than in specific markers. We have used this approach to quantitatively track tissue architecture during adulthood and aging in the C. elegans pharynx, the neuromuscular feeding organ. Using pattern recognition to analyze aged-grouped pharynx images, we identified discrete step-wise transitions between distinct morphologies. The morphology state transitions were maintained in mutants with pharynx neurotransmission defects, although the pace of the transitions was altered. Longitudinal measurements of pharynx function identified a predictive relationship between mid-life pharynx morphology and function at later ages. These studies demonstrate for the first time that adult tissues undergo distinct structural transitions reflecting postdevelopmental events. The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate. This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers.

Show MeSH
Related in: MedlinePlus