More Intestinal AMPK Extends Life in Flies via Autophagy

Intestinal function is especially important in fly aging, and of late a number of ways of extending life in fly studies have involved interventions targeted to intestinal tissue, including altered levels of PGC-1 and improved stem cell function via altered insulin signaling. Further, it was recently established that INDY, an early longevity gene discovery in flies, also works via improved intestinal stem cell function.

The gene AMPK turns up in many studies of methods known to slow aging in laboratory species: you might peruse the Fight Aging! archives for a fair sized selection. AMPK is centrally placed in numerous core mechanisms of metabolism that are altered by these existing ways to slow aging, but it is especially important as an activator of the cellular housekeeping processes of autophagy. More autophagy generally leads to longer life in animal studies for all of the obvious reasons: less damage means less dysfunction. Here researchers show that increased AMPK levels in fly intestines extend healthy life:

Working with fruit flies, the life scientists activated a gene called AMPK that is a key energy sensor in cells; it gets activated when cellular energy levels are low. Increasing the amount of AMPK in fruit flies' intestines increased their lifespans by about 30 percent - to roughly eight weeks from the typical six - and the flies stayed healthier longer as well. "We have shown that when we activate the gene in the intestine or the nervous system, we see the aging process is slowed beyond the organ system in which the gene is activated."

The findings are important because extending the healthy life of humans would presumably require protecting many of the body's organ systems from the ravages of aging - but delivering anti-aging treatments to the brain or other key organs could prove technically difficult. The study suggests that activating AMPK in a more accessible organ such as the intestine, for example, could ultimately slow the aging process throughout the entire body, including the brain. Humans have AMPK, but it is usually not activated at a high level.

"Instead of studying the diseases of aging - Parkinson's disease, Alzheimer's disease, cancer, stroke, cardiovascular disease, diabetes - one by one, we believe it may be possible to intervene in the aging process and delay the onset of many of these diseases. We are not there yet, and it could, of course, take many years, but that is our goal and we think it is realistic. The ultimate aim of our research is to promote healthy aging in people."

"A really interesting finding was when [we] activated AMPK in the nervous system, he saw evidence of increased levels of autophagy in not only the brain, but also in the intestine. And vice versa: Activating AMPK in the intestine produced increased levels of autophagy in the brain - and perhaps elsewhere, too." Many neurodegenerative diseases, including both Alzheimer's and Parkinson's, are associated with the accumulation of protein aggregates, a type of cellular garbage, in the brain. "[We] moved beyond correlation and established causality. [We] showed that the activation of autophagy was both necessary to see the anti-aging effects and sufficient; that [we] could bypass AMPK and directly target autophagy."



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