Abstract
Sodium is an essential nutrient, but it can be toxic in excess. In humans, excessive ingestion of dietary sodium is a prevalent cause of high blood pressure, which contributes to age-related diseases including stroke and heart disease. To elucidate how sodium levels influence animal aging, we used C. elegans, a powerful model system to study development and aging. Most experiments on this animal are conducted in standard culture conditions: Nematode Growth Medium (NGM) agar with a lawn of E. coli. Here we present evidence that NaCl in standard NGM accelerates age-related degeneration and decreases lifespan. Standard NGM contains 50 mM supplemental NaCl. For comparison, we prepared NGM with reduced NaCl or excess NaCl. Considering reduced NaCl as a baseline, wild-type worms cultured on standard NaCl displayed a normal rate of development and fertility, indicating young animals are minimally affected, but they displayed decreased lifespan and health span, indicating toxicity in older animals. The long-lived mutants daf-2, age-1, and nuo-6, cultured on NGM with standard NaCl, also displayed decreased lifespan. Thus, the level of NaCl in standard medium accelerates aging in multiple genetic backgrounds. Wild-type worms cultured with excess NaCl displayed delayed development and reduced fertility, indicating toxicity in young animals, and decreased lifespan and health span, indicating toxicity old animals. These results suggest that young animals are relatively resistant to NaCl toxicity, thriving in reduced and standard NaCl levels and only displaying toxicity in excess NaCl. Aging causes progressive sensitivity to NaCl toxicity, so that old animals display toxicity in both standard and excess NaCl. To investigate pathways that respond to NaCl, we examined five stress reporters. Young animals cultured with excess NaCl displayed transcriptional activation of gpdh-1, a specific response to NaCl stress. Old animals cultured with excess NaCl displayed transcriptional activation of gpdh-1 and hsp-6, a reporter for the mitochondrial unfolded protein response. Thus, excess NaCl activates multiple stress response pathways in older animals.
Competing Interest Statement
The authors have declared no competing interest.
