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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.

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Image analysis identified morphological features correlated to pharynx function during aging.(A) Longitudinal pumping data are shown for individual animals sorted into low, medium, and high LPA ranges. Each animal's trace has a colored portion based on its LPA score that ends on the last day the individual was observed alive, and a horizontal grey portion that ends on the day the individual was observed dead. The light grey background lines depict pump rates measured for the entire population. Colors correspond to actual LPA value for each individual as depicted in the heatmap. The rectangles designate the actual LPA values for the individual data highlighted in the lower plots. These figures show that pump rates can have significant day-to-day variation, and that LPA values were positively correlated with pharynx function and healthspan after day 6. (B) Correlation between morphological differences and differences in future function was established by measuring distance between each pair of images in the LPA classifier's marginal probability space, and comparing it to the corresponding difference in LPA values. (C) Dendrogram representing image similarity. 91 images are represented by branch endpoints with their relative positions predicted by the model. Endpoint colors indicate the LPA value for each image; branch colors are determined from the relative contributions of neighboring endpoints. This dendrogram shows that the LPA classifier was able to correctly order images with respect to their measured LPA values, from low (red and orange) to high (blue), as designated in part (A). (D) Representative images show a progression from high to low levels of structural deterioration that corresponds to their measured LPA values.
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pone-0002821-g006: Image analysis identified morphological features correlated to pharynx function during aging.(A) Longitudinal pumping data are shown for individual animals sorted into low, medium, and high LPA ranges. Each animal's trace has a colored portion based on its LPA score that ends on the last day the individual was observed alive, and a horizontal grey portion that ends on the day the individual was observed dead. The light grey background lines depict pump rates measured for the entire population. Colors correspond to actual LPA value for each individual as depicted in the heatmap. The rectangles designate the actual LPA values for the individual data highlighted in the lower plots. These figures show that pump rates can have significant day-to-day variation, and that LPA values were positively correlated with pharynx function and healthspan after day 6. (B) Correlation between morphological differences and differences in future function was established by measuring distance between each pair of images in the LPA classifier's marginal probability space, and comparing it to the corresponding difference in LPA values. (C) Dendrogram representing image similarity. 91 images are represented by branch endpoints with their relative positions predicted by the model. Endpoint colors indicate the LPA value for each image; branch colors are determined from the relative contributions of neighboring endpoints. This dendrogram shows that the LPA classifier was able to correctly order images with respect to their measured LPA values, from low (red and orange) to high (blue), as designated in part (A). (D) Representative images show a progression from high to low levels of structural deterioration that corresponds to their measured LPA values.

Mentions: An important issue for understanding the biology of aging is defining whether changes associated with early aging can correlate reliably to future aging success. We addressed this question for the C. elegans pharynx by searching for longitudinal correlations between mid-life morphology and future functional decline. First, we measured pharynx pump rates and collected pharynx images from day 6 adults, an age where the population exhibits a wide variation in pump rate due to heterogeneous functional declines [15]. It was also felt that day 6 animals would be better able to tolerate the imaging procedure than older animals (see Methods). Following image acquisition, animals were recovered and pharynx pump rates were determined every few days until death. As expected, average pharynx pump rate in the population declined continuously during aging. However, we found that pump rates of individual animals exhibited substantial daily variation. This variation in day-to-day pump rates interfered with comparisons of pharynx function between animals. Therefore, we derived a composite measure of pharynx pump rate over lifetime, which we refer to as lifetime pumping ability (LPA). First, Z-scores were calculated that reflected individual deviation away from the population mean pump rate on each day. Then, an average was taken of each animal's Z-scores over the individual's lifetime to arrive at the LPA. Thus, the LPA provides a relative measure of pharynx function from day 6 onward while minimizing the effects of daily fluctuations. Comparisons of LPA with daily pump rate observations indicated that LPA was positively correlated with pharynx function after day 6 (Fig. 6A).


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)

Image analysis identified morphological features correlated to pharynx function during aging.(A) Longitudinal pumping data are shown for individual animals sorted into low, medium, and high LPA ranges. Each animal's trace has a colored portion based on its LPA score that ends on the last day the individual was observed alive, and a horizontal grey portion that ends on the day the individual was observed dead. The light grey background lines depict pump rates measured for the entire population. Colors correspond to actual LPA value for each individual as depicted in the heatmap. The rectangles designate the actual LPA values for the individual data highlighted in the lower plots. These figures show that pump rates can have significant day-to-day variation, and that LPA values were positively correlated with pharynx function and healthspan after day 6. (B) Correlation between morphological differences and differences in future function was established by measuring distance between each pair of images in the LPA classifier's marginal probability space, and comparing it to the corresponding difference in LPA values. (C) Dendrogram representing image similarity. 91 images are represented by branch endpoints with their relative positions predicted by the model. Endpoint colors indicate the LPA value for each image; branch colors are determined from the relative contributions of neighboring endpoints. This dendrogram shows that the LPA classifier was able to correctly order images with respect to their measured LPA values, from low (red and orange) to high (blue), as designated in part (A). (D) Representative images show a progression from high to low levels of structural deterioration that corresponds to their measured LPA values.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2483734&req=5

pone-0002821-g006: Image analysis identified morphological features correlated to pharynx function during aging.(A) Longitudinal pumping data are shown for individual animals sorted into low, medium, and high LPA ranges. Each animal's trace has a colored portion based on its LPA score that ends on the last day the individual was observed alive, and a horizontal grey portion that ends on the day the individual was observed dead. The light grey background lines depict pump rates measured for the entire population. Colors correspond to actual LPA value for each individual as depicted in the heatmap. The rectangles designate the actual LPA values for the individual data highlighted in the lower plots. These figures show that pump rates can have significant day-to-day variation, and that LPA values were positively correlated with pharynx function and healthspan after day 6. (B) Correlation between morphological differences and differences in future function was established by measuring distance between each pair of images in the LPA classifier's marginal probability space, and comparing it to the corresponding difference in LPA values. (C) Dendrogram representing image similarity. 91 images are represented by branch endpoints with their relative positions predicted by the model. Endpoint colors indicate the LPA value for each image; branch colors are determined from the relative contributions of neighboring endpoints. This dendrogram shows that the LPA classifier was able to correctly order images with respect to their measured LPA values, from low (red and orange) to high (blue), as designated in part (A). (D) Representative images show a progression from high to low levels of structural deterioration that corresponds to their measured LPA values.
Mentions: An important issue for understanding the biology of aging is defining whether changes associated with early aging can correlate reliably to future aging success. We addressed this question for the C. elegans pharynx by searching for longitudinal correlations between mid-life morphology and future functional decline. First, we measured pharynx pump rates and collected pharynx images from day 6 adults, an age where the population exhibits a wide variation in pump rate due to heterogeneous functional declines [15]. It was also felt that day 6 animals would be better able to tolerate the imaging procedure than older animals (see Methods). Following image acquisition, animals were recovered and pharynx pump rates were determined every few days until death. As expected, average pharynx pump rate in the population declined continuously during aging. However, we found that pump rates of individual animals exhibited substantial daily variation. This variation in day-to-day pump rates interfered with comparisons of pharynx function between animals. Therefore, we derived a composite measure of pharynx pump rate over lifetime, which we refer to as lifetime pumping ability (LPA). First, Z-scores were calculated that reflected individual deviation away from the population mean pump rate on each day. Then, an average was taken of each animal's Z-scores over the individual's lifetime to arrive at the LPA. Thus, the LPA provides a relative measure of pharynx function from day 6 onward while minimizing the effects of daily fluctuations. Comparisons of LPA with daily pump rate observations indicated that LPA was positively correlated with pharynx function after day 6 (Fig. 6A).

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