“Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear,” write the scientists in a study (“Spatiotemporal Regulation of Autophagy during Caenorhabditis elegansAging”) published in eLife. “Using a GFP [green fluorescent protein]-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood. Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals.”
Researchers at the Sanford Burnham Prebys Medical Discovery Institute (SBP) have now discovered how autophagy becomes faulty with age and have learnt that studying this process which basically is a recycling process that becomes incomplete with age by stopping somewhere after APs are formed, may reveal opportunities for us to therapeutically intervene and correct the process to promote health aging.
And to study this process carefully, the scientists proceeded with the investigation on the nematode worm C. Elegans, which is agreeably a powerful tool for research studies as it shares many of the same anatomic and cell functions as humans, and its short lifespan (average 17 days) enables scientists to study
genes and measure cell traits in just two to three weeks.Previous studies by Malene Hansen, Ph.D., professor in the development, aging, and regeneration program at SBP have suggested an increase in APs with age, but since the measurements were taken under steady-state conditions, it was not clear what step(s) in the process led to increased levels.
Therefore in this recent study, the group went beyond the standard approach of counting APs under steady-state conditions and counted the numbers of APs and ALs in different body tissues—intestine, muscle, pharynx (i.e., the animal’s foregut), and neurons—at different time points during the adult life of C. elegans, and used chemical blockers to learn more about the dynamics of the process.
“We found that there is indeed an age-dependent decline in autophagy over time in all tissues examined. We further provide evidence that the increase in APs results from an impairment at a step after APs are made,” says Dr. Hansen. “So basically the autophagy recycling process becomes incomplete with age by stopping somewhere after APs are formed.”
“This research is important because it helps provide time- and site-of-action information for potential future interventions directed at sustaining autophagy to extend lifespan. Our next step will be to perform biochemical research to further pinpoint exactly how autophagy fails to complete its cycle, possibly providing targets to develop specific interventions.”
In the future, the team “hopes to find ways to correct the defects and find ways to help people live longer, healthier lives.”
