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. 2004 May 25;101(21):8084-9.
doi: 10.1073/pnas.0400848101. Epub 2004 May 12.

Measurements of age-related changes of physiological processes that predict lifespan of Caenorhabditis elegans

Cheng Huang  1 , Chengjie Xiong, Kerry Kornfeld
Affiliations

Measurements of age-related changes of physiological processes that predict lifespan of Caenorhabditis elegans

Cheng Huang et al. Proc Natl Acad Sci U S A. .

Abstract

Aging is characterized by progressive, degenerative changes in many tissues. To elucidate the relationships among degenerative changes in Caenorhabditis elegans, we developed methods to measure age-related changes quantitatively and analyzed correlations among these changes by using a longitudinal study. The age-related declines of pharyngeal pumping and body movement were positively correlated with each other and lifespan. These findings suggest that the declines of pharyngeal pumping and body movement cause a decline in survival probability or that a shared regulatory system mediates the declines in pharyngeal pumping, body movement, and survival probability. Furthermore, measurements of these processes can be used to predict lifespan and detect premature aging. The declines of physiological processes were measured in daf-2, age-1, daf-16, eat-2, and clk-1 mutants that have altered lifespans. Each mutant strain displayed changes in one or more age-related declines, but the correlations among age-related changes were similar to WT. These measurements were used to generate a system of four stages that describes the aging process and is useful for the analysis of genetic and environmental effects on aging.

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Figures

Fig. 1.
Fig. 1.
Age-related change of pharyngeal pumping rate. Day zero animals were WT L4 hermaphrodites. Vertical bars represent the average number of pharyngeal contractions per minute and the standard deviation for live animals on each day (n = 11 animals on day zero and fewer animals on later days). The standard deviation of replicate measurements of day 2 individuals is ≈9% of the average value, indicating that the most of the variability is due to differences between individuals.
Fig. 2.
Fig. 2.
Mutations of daf-2, age-1, daf-16, eat-2, and clk-1 affect specific aging phenotypes. (A) WT L4 hermaphrodites were placed on individual Petri dishes and monitored for self-progeny production, fast body movement, fast pharyngeal pumping, any pharyngeal pumping, and survival. The percent of animals in the population (n = 180) that displayed the phenotype is graphed versus time in days. (B–E) Mutant animals were analyzed similarly to WT animals. Table 1 shows the alleles, number of animals analyzed, and calculated mean values. The plots show self-fertile reproduction (B), fast body movement (C), fast pharyngeal pumping (D), pharyngeal pumping (E), and survival (F) versus age in days.
Fig. 3.
Fig. 3.
Longitudinal analysis of correlations between the declines of physiological processes and lifespan. Each point represents data for one WT hermaphrodite or more than one hermaphrodite in cases where multiple animals had identical values (n = 180). The lifespan and self-fertile reproductive (A), fast body movement (B), fast pharyngeal pumping (C), and pharyngeal pumping (D) spans are shown.
Fig. 4.
Fig. 4.
Stages of C. elegans aging. (A) Horizontal bars represent the average time in days spent in stages I–IV (described in text). The mutant alleles, number of animals analyzed, and mean values for age-related traits are shown in Table 1. Animals were analyzed at 20°C except for WT 15°C. (B) The fraction of the mean lifespan occupied by each stage was calculated by setting the mean lifespan equal to 100%.
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