Over the previous decade, researchers have put a substantial amount of effort into automating and in any other case decreasing the prices of research of growing older in nematode worms. A correctly outfitted workforce can now display screen hundreds of compounds in a yr in nematodes, whereas acquiring good information on life span and tempo of decline with age by way of a variety of metrics. Sadly, short-lived species resembling nematodes have life spans which might be much more plastic in response to interventions than is the case for longer-lived species resembling our personal. A ten-20% enhance in nematode life span is probably going irrelevant to people; some interventions that in all probability do little in people have elevated nematode life span by 100% or extra. It’s value bearing this in thoughts when studying papers such because the one famous right here.
There may be growing curiosity within the idea of growing older as a druggable goal to forestall age-related illnesses. Nonetheless, growing new medicine to handle human growing older presents challenges in conducting scientific trials. Within the absence of validated threat biomarkers, a big and initially wholesome inhabitants would have to be handled over an prolonged interval, making it troublesome to conduct trials. Due to this fact, repurposing present medicine with a very good security profile is a extra sensible short-term answer than growing new medicine.
Naltrexone is a prescription remedy accepted by the US Meals and Drug Administration (FDA) in 1984 for the remedy of alcohol use dysfunction and opioid use dysfunction. It belongs to a category of medication referred to as opioid antagonists. Lately, there have been a number of important findings concerning a selected dosage of naltrexone referred to as low-dose naltrexone (LDN). LDN has been proven to have immune-modulating properties that would scale back varied oncogenic and inflammatory autoimmune processes and alleviate signs of sure psychological illnesses.
Right here, we studied the potential advantages of low-dose naltrexone (LDN) in selling wholesome growing older utilizing Caenorhabditis elegans as a mannequin organism. We discovered that LDN remedy prolonged each healthspan and lifespan in worms, whereas high-dose naltrexone didn’t produce the identical results. Additional metabolomics evaluation revealed that LDN remedy induced metabolic adjustments that led to elevated exercise of each amino acid and glucose metabolism, however the longevity impact was impartial of the DAF-16/FOXO3 signaling.
We then examined varied mutant strains and located that the lifespan extension induced by LDN remedy was depending on the SKN-1/NRF2 transcription issue. We additionally noticed that LDN remedy not solely elevated the expression of innate immune genes but additionally upregulated the oxidative stress response, in step with a task for SKN-1/NRF2 in LDN’s lifespan selling results. Inhibiting the nuclear translocation of SKN-1 from the cytosol might attenuate the LDN-mediated innate immune gene expression and oxidative stress response. General, our research highlights the potential of LDN as a therapeutic agent for selling wholesome growing older and identifies its mechanism of motion.
Hyperlink: https://doi.org/10.1016/j.isci.2024.109949
