The insulin and insulin-like signaling (IIS) pathways and the target of rapamycin (TOR) pathway are critical elements of the aging process. Findings from a new study suggest that decreasing the activity of these highly conserved pathways markedly increases the lifespan of worms.
The IIS pathways are involved in maintaining glucose homeostasis. They facilitate the uptake of glucose into fat and muscle cells while inhibiting gluconeogenesis – the production of glucose in the liver. These pathways are dysregulated in obesity and type 2 diabetes.
The TOR pathway senses amino acid concentrations and regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. It integrates other pathways including insulin, growth factors (such as IGF-1), and amino acids and plays a key role in mammalian metabolism and physiology. The pathway is dysregulated in many human diseases, such as diabetes, obesity, depression, and certain cancers.
The study focused on altering the activity of orthologs of these pathways (called DAF-2 and RSKS-1) in C. elegans, a type of nematode worm, which is often used in aging studies. The authors of the study introduced double mutations in the worms to block the activities of DAF-2 and RSKS-1 and conducted genome-wide translational state analysis to identify genes associated with the worms' lifespan.
Knocking DAF-2 and RSK-1 elicited a synergistic effect that increased the lifespan of the worms by 500 percent, suggesting that regulation of these two pathways is integral to the aging process in worms. Watch this clip for learn more about the evidence that altered growth hormone and insulin signaling may improve healthspan in humans, too.