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

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.T he identification and measurement of age-related changes, or markers of aging, is a major element of aging research. It is necessary because an understanding of the aging process requires a description of the specific changes that occur. Furthermore, many of the hypotheses about the cause of aging are based on the identification of an age-related change. Because age-related changes are widespread, it is particularly important to determine the relationships among these changes and identify age-related changes that affect lifespan. Three main experimental approaches can be used to investigate these relationships. Longitudinal studies that include serial measurements of the same individual can identify correlations among age-related changes that are measured at different times in the lifespan (1, 2). Cross-sectional studies that include one evaluation of each individual can identify correlations among age-related changes that are measured at the same time in the lifespan. Both longitudinal and cross-sectional data can be used to analyze correlations by comparing two or more populations of animals that have different aging properties as a result of genetic or environmental factors (3, 4). Longitudinal studies provide the most information about the relationships among changes that occur at different times in the lifespan, but longitudinal studies have not been performed frequently because they require substantial time and effort. Here we used longitudinal studies to analyze the relationships among age-related declines of physiological processes and lifespan of the nematode Caenorhabditis elegans.C. elegans is an important model organism for aging research, because it has a short lifespan, and many mutations have been identified that extend the adult lifespan (reviewed by Kenyon in ref. 5). The most extensively char...

Movement decline across lifespan of Caenorhabditis elegans mutants in the insulin/insulin‐like signaling pathway

“…Diminishing movement as a function of age has been documented in multiple studies (Bolanowski, Russell, & Jacobson, 1981; Glenn et al., 2004; Herndon et al., 2002; Huang, Xiong, & Kornfeld, 2004; Johnson, 1987). Here, we use a method similar to that of Hosono, Sato, Aizawa, and Mitsui (1980) and Herndon et al.…”

“…Retention of Class A movement has been used as a marker of extended healthspan (Herndon et al., 2002; Huang et al., 2004). We observed that long‐lived mutants generally retain Class A behavior longer (Figures 3 and 4).…”

“…Study of the age‐related loss of movement has been well documented in C. elegans and has been used as a marker of healthspan (Bolanowski et al., 1981; Duhon & Johnson, 1995; Glenn et al., 2004; Herndon et al., 2002; Honda & Honda, 2002; Hosono et al., 1980; Hsu, Feng, Hsieh, & Xu, 2009; Huang et al., 2004; Johnson, 1987; Shook, Brooks, & Johnson, 1996). Mechanisms of movement decline include structural and molecular changes resembling human sarcopenia (decrease in size and number of muscle cells, fraying of fibers, and loss of sarcomere integrity, Herndon et al., 2002), reduced neuronal signaling (Liu et al., 2013), and changes in exploratory behaviors (Hahm et al., 2015).…”

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

“…(2004), except that the N2 worms used were selected at random from the populations within the lifespan assay. For the movement assay, the plates were firmly tapped onto the microscope to stimulate movement.…”

Lifespan extension and increased pumping rate accompany pharyngeal muscle‐specific expression of nfi‐1 in C. elegans

“…While cause and effect cannot be directly inferred from these data, the correlation between pharyngeal pumping rescue and lifespan extension is striking and warrants further investigation. Previous studies indicated that a reduced rate of pharyngeal pumping was highly correlated to organismal aging in C. elegans (Huang et al, 2004). Pumping rates decrease with age in wild-type animals and mutations that affect lifespan concomitantly affect pumping rates (Huang et al, 2004).…”