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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 revealed altered morphology states in slow-pumping eat-2(ad465) animals and serotonin-deficient tph-1(mg280) animals.(A) Age-scores assigned by a model trained on fem-1(hc17) days 0 to 12 for test images from normal and mutant animals were formatted the same way as Fig 3(B). The number of test images for each age class ranged between 68 and 117. (B) Probability distributions of fem-1(hc17), tph-1(mg280), and eat-2(ad465) age scores from days 0, 2, 4 and 6 from (A). A slight rightward shift is noted in day 6 eat-2(ad465) images. The images of tph-1(mg280) adults attained higher-than-normal age scores at all ages except day 6, possibly reflecting aberrant morphology. (C) Representative images of each strain at ages 2 and 8 were selected as having age scores (AS) near the population means. Lower left image of tph-1(mg280) day 2 pharynx reveals aberrant morphology. Lower right image of day 8 tph-1(mg280) shows structural deformation similar to that seen in day 8 fem-1(h17) and eat-2(ad465) animals.
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pone-0002821-g005: Image analysis revealed altered morphology states in slow-pumping eat-2(ad465) animals and serotonin-deficient tph-1(mg280) animals.(A) Age-scores assigned by a model trained on fem-1(hc17) days 0 to 12 for test images from normal and mutant animals were formatted the same way as Fig 3(B). The number of test images for each age class ranged between 68 and 117. (B) Probability distributions of fem-1(hc17), tph-1(mg280), and eat-2(ad465) age scores from days 0, 2, 4 and 6 from (A). A slight rightward shift is noted in day 6 eat-2(ad465) images. The images of tph-1(mg280) adults attained higher-than-normal age scores at all ages except day 6, possibly reflecting aberrant morphology. (C) Representative images of each strain at ages 2 and 8 were selected as having age scores (AS) near the population means. Lower left image of tph-1(mg280) day 2 pharynx reveals aberrant morphology. Lower right image of day 8 tph-1(mg280) shows structural deformation similar to that seen in day 8 fem-1(h17) and eat-2(ad465) animals.

Mentions: We next examined whether the model could robustly detect pharynx morphology differences between normal (fem-1(hc17)) adults and mutants with defects in pharynx function. Early versions of the classifier software were able to distinguish a slow-aging appearance in pharynx images from long-lived strains carrying mutations in the daf-2 gene, encoding an insulin-receptor like protein (Fig. S1) [14]. Since delayed aging in the daf-2/insulin-like pathway mutants has been extensively documented, and likely involves hormonal control of aging in all tissues [1], [3], [15], [16], we turned our attention to mutants that more directly affect pharynx function. First, we examined pharynx morphology during aging of eat-2(ad465) animals, which lack function of a pharyngeal nicotinic acetylcholine receptor subunit [17]. The terminal bulb contraction rate in eat-2(ad465) adults is 75% slower than normal. This slow pump rate causes dietary restriction, prolonging lifespan in eat-2(ad465) adults by 30% [18]. Previous analysis had indicated that aging-associated pharynx structural decline was delayed in eat-2(ad465) animals [15]. This effect could be due to either dietary restriction's benefits or protective effects of slow pumping. To directly compare the previous analysis with the computational approach, we built a model trained on pharynx images from normal day 2 and 8 animals, and used it to score pharynx images from day 2 and 8 eat-2(ad465) adults. This approach showed statistically significant lower scores between eat-2(ad465) and normal pharynx terminal bulbs at adult day 8 (p = 0.014), indicating that the computational approach was consistent with human-based scoring in a side-by-side comparison (Fig. 4). However, scoring eat-2(ad465) pharynx images from all available ages (days 0–8) using the complete fem-1(hc17) model (days 0–12) showed that eat-2(ad465) images scored significantly younger only at day 6 (p = 0.04, one-tailed t-test), with a small downward trend at day 2 (Fig. 5). These results demonstrate that the computational model allows construction of more complex visual assessments than human-based scoring when quantifying the relative differences in morphology between these strains. Further, the model's results provide a more quantitative assessment of the relatively modest effect of the eat-2(ad465) mutation on pharynx muscle aging.


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 revealed altered morphology states in slow-pumping eat-2(ad465) animals and serotonin-deficient tph-1(mg280) animals.(A) Age-scores assigned by a model trained on fem-1(hc17) days 0 to 12 for test images from normal and mutant animals were formatted the same way as Fig 3(B). The number of test images for each age class ranged between 68 and 117. (B) Probability distributions of fem-1(hc17), tph-1(mg280), and eat-2(ad465) age scores from days 0, 2, 4 and 6 from (A). A slight rightward shift is noted in day 6 eat-2(ad465) images. The images of tph-1(mg280) adults attained higher-than-normal age scores at all ages except day 6, possibly reflecting aberrant morphology. (C) Representative images of each strain at ages 2 and 8 were selected as having age scores (AS) near the population means. Lower left image of tph-1(mg280) day 2 pharynx reveals aberrant morphology. Lower right image of day 8 tph-1(mg280) shows structural deformation similar to that seen in day 8 fem-1(h17) and eat-2(ad465) animals.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2483734&req=5

pone-0002821-g005: Image analysis revealed altered morphology states in slow-pumping eat-2(ad465) animals and serotonin-deficient tph-1(mg280) animals.(A) Age-scores assigned by a model trained on fem-1(hc17) days 0 to 12 for test images from normal and mutant animals were formatted the same way as Fig 3(B). The number of test images for each age class ranged between 68 and 117. (B) Probability distributions of fem-1(hc17), tph-1(mg280), and eat-2(ad465) age scores from days 0, 2, 4 and 6 from (A). A slight rightward shift is noted in day 6 eat-2(ad465) images. The images of tph-1(mg280) adults attained higher-than-normal age scores at all ages except day 6, possibly reflecting aberrant morphology. (C) Representative images of each strain at ages 2 and 8 were selected as having age scores (AS) near the population means. Lower left image of tph-1(mg280) day 2 pharynx reveals aberrant morphology. Lower right image of day 8 tph-1(mg280) shows structural deformation similar to that seen in day 8 fem-1(h17) and eat-2(ad465) animals.
Mentions: We next examined whether the model could robustly detect pharynx morphology differences between normal (fem-1(hc17)) adults and mutants with defects in pharynx function. Early versions of the classifier software were able to distinguish a slow-aging appearance in pharynx images from long-lived strains carrying mutations in the daf-2 gene, encoding an insulin-receptor like protein (Fig. S1) [14]. Since delayed aging in the daf-2/insulin-like pathway mutants has been extensively documented, and likely involves hormonal control of aging in all tissues [1], [3], [15], [16], we turned our attention to mutants that more directly affect pharynx function. First, we examined pharynx morphology during aging of eat-2(ad465) animals, which lack function of a pharyngeal nicotinic acetylcholine receptor subunit [17]. The terminal bulb contraction rate in eat-2(ad465) adults is 75% slower than normal. This slow pump rate causes dietary restriction, prolonging lifespan in eat-2(ad465) adults by 30% [18]. Previous analysis had indicated that aging-associated pharynx structural decline was delayed in eat-2(ad465) animals [15]. This effect could be due to either dietary restriction's benefits or protective effects of slow pumping. To directly compare the previous analysis with the computational approach, we built a model trained on pharynx images from normal day 2 and 8 animals, and used it to score pharynx images from day 2 and 8 eat-2(ad465) adults. This approach showed statistically significant lower scores between eat-2(ad465) and normal pharynx terminal bulbs at adult day 8 (p = 0.014), indicating that the computational approach was consistent with human-based scoring in a side-by-side comparison (Fig. 4). However, scoring eat-2(ad465) pharynx images from all available ages (days 0–8) using the complete fem-1(hc17) model (days 0–12) showed that eat-2(ad465) images scored significantly younger only at day 6 (p = 0.04, one-tailed t-test), with a small downward trend at day 2 (Fig. 5). These results demonstrate that the computational model allows construction of more complex visual assessments than human-based scoring when quantifying the relative differences in morphology between these strains. Further, the model's results provide a more quantitative assessment of the relatively modest effect of the eat-2(ad465) mutation on pharynx muscle aging.

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