Aging is something we all have in common. Over the past decade, tremendous breakthroughs have been made towards scientifically understanding mechanisms that control aging.
For nearly a century scientists have known that regulation of metabolism and energy production through dietary restriction could extend lifespan in various species, including a 20-year study in rhesus monkeys reported in 2009. Since neurodegenerative diseases are often classified as diseases of aging, it is commonly believed that slowing aging would have positive effects on neuronal health.
A team led by J. Alex Parker, PhD at Université de Montréal has revealed new evidence that higher glucose (sugar) intake, which shortens lifespan in multiple organisms and causes several disorders in humans (type 2 diabetes, obesity, cardiovascular disease), is actually neuroprotective in worm models of ALS. Their manuscript, recently accepted for publication in the journal Aging Cell calls into question the link between the potential for increasing lifespan with the potential to decrease neurodegeneration.
Earlier this year, Parker’s lab established that tiny roundworms called C. elegans developed an adult-onset movement disorder with protein clumps, neuronal degeneration and paralysis similar to human ALS when they were altered to make mutant forms of the proteins TDP-43 and FUS. Both TDP-43 and FUS mutations have been linked to ALS in humans. Using these worms, they discovered that reducing their food intake, a process well known to increase worm lifespan, had no effect on the ALS-like condition, yet placing them on a glucose enriched diet, which shortens worm lifespan, reduced all of the ALS-like symptoms. This study also proved that the utilization of glucose to produce energy through a process called glycolysis (which is also a key pathway in humans) is essential to this neuroprotection, as are known factors that influence the removal of protein clumps that are a prominent feature of ALS. With that discovery, Parker establishes the novel concept that “glucose achieves neuroprotection by reducing the levels of misfolded mutant proteins within the cell.” He further shared, “It’s too early to know, but the fact that we can reduce neurodegeneration in simple models by adjusting their diet gives us hope that perhaps a similar mechanism exists in ALS patients”.
Parker summarizes that this work demonstrates “the negative effects on lifespan from excessive glucose can be separated from neuroprotection”. Undoubtedly, these results highlight the need for careful study of the differences between diseased and aging neurons and emphasize the importance of understanding the delicate balance of glucose metabolism required to slow neurodegeneration without achieving the known side effects associated with glucose enriched diets.
Tauffenberger A, Vaccaro A, Aulas A, Vande Velde C and Parker JA. (2012) Glucose delays age-dependent proteotoxicity. Aging Cell. published online June 26, 2012.
To download a copy of the manuscript, click here: http://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2012.00855.x/abstract;jsessionid=427CB9D612F722961A13ABE5176AB6F3.d02t01?systemMessage=Wiley +Online+Library+will+be+disrupted+on+7+July+from+10%3A00-12%3A00+BST+%2805%3A00-07%3A00+EDT%29+for+essential+maintenance
To access J. Alex Parker’s C. elegans ALS model manuscript click here: