A cellular surveillance and defense system that delays aging phenotypes in C. elegans.
Aging is an important risk factor for disease and is accompanied by the decline of many physiological characteristics, including physical performance. One of the most powerful tests of physical ability in elderly humans is the short physical performance battery (SPPB) (Guralnik et al., 1994), an assessment of the maximum exercise capacity of lower extremities over a short period of time. A similar metric of maximum velocity (MV) in a short period (30s) is proposed as an equally informative measurement inC. elegans (Hahm et al., 2015). MV declines with age, correlates well with longevity, accurately reports movement ability, and importantly, is predictive of future longevity (Hahm et al., 2015).Here, we characterized the differences in gene expression between high MV group and low MV group of the same age in C. elegans. The genes related to nucleosomes and involved in regulatory processes, including transcriptional regulation (chromatin assembly, regulation of RNA metabolic process and regulation of transcription), and neuronal signaling (neurogenesis, axon guidance, and regulation of neurotransmitter levels) were up-regulated in low MV group compared to high MV group. In contrast, genes belonged to metabolic processes and mitochondria were down-regulated in low MV group compared to high MV group.
Age-related behaviors have distinct transcriptional profiles in C. elegans
There has been a great deal of interest in identifying potential biomarkers of aging (Butler et al. 2004). Biomarkers of aging would be useful to predict potential vulnerabilities in an individual that may arise well before they are chronologically expected, due to idiosyncratic aging rates that occur between individuals. Prior attempts to identify biomarkers of aging have often relied on the comparisons of long-lived animals to a wild-type control (Dhahbi et al. 2004). However, the effect of interventions in model systems that prolong lifespan (such as single gene mutations, or caloric restriction) can sometimes be difficult to interpret due to the manipulation itself having multiple unforeseen consequences on physiology, unrelated to aging itself (Gems et al. 2002; Partridge & Gems 2006). The search for predictive biomarkers of aging therefore is problematic, and the identification of metrics that can be used to predict either physiological or chronological age would be of great value (Butler et al. 2004). One methodology which has been used to identify biomarkers for numerous pathologies is gene expression profiling. Here, we report whole-genome expression profiles of individual wild-type Caenorhabditis elegans covering the entire wild-type nematode life span. Individual nematodes were scored for either age-related behavioral phenotypes, or survival, and then subsequently associated with their respective gene expression profiles. This facilitated the identification of transcriptional profiles that were highly associated with either physiological or chronological age. Overall, our approach serves as a paradigm for identifying potential biomarkers of aging in higher organisms that can be repeatedly sampled throughout their lifespan. The full normalized data set with expression values for all genes of all individual worms at all ages (104 worms/arrays) is available as a 28Mb download as a supplementary file on this page (GSE12290.txt). Keywords: time couse