Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 16 No. 3 • March 2013

Revenge of the Fly: The Relationship Between Intestinal Health, Aging, and Death

Note: If you have not seen the movie The Fly, skip the introductory paragraph below.

In setting the scene for the important health information that follows, please note: If you have recently entered a box looking like a weird telephone booth (but not a Tardis) and ended up with your head on a fly’s body (or, worse yet, your body with a fly’s head), the following health information may apply to you. On the other hand, even if you haven’t done anything remotely like this (and we certainly hope you haven’t), it still might apply to you. This silly introduction is just for fun, but the research is real.

A new paper1 in the December 26, 2012 Proceedings of the National Academy of Sciences USA reports that intestinal barrier dysfunction links metabolic and inflammatory markers to aging in Drosophila (“the fly”). Most remarkably, however, the paper provides evidence that “[r]egardless of chronological age, intestinal barrier dysfunction predicts impending death in individual flies.” “Thus, intestinal barrier dysfunction appears to be a better predictor of this marker of aging [increased expression of antimicrobial peptides, AMP] than chronological age.” Elie Metchnikoff, a very early investigator of the causes of aging, thought that intestinal health was an important factor in aging and recommended yogurt consumption.2

The researchers reported in an earlier paper of theirs that the loss of intestinal barrier function could be detected by the presence of a nonabsorbable blue food dye (FD&C blue dye no. 1) outside of the intestinal tract. As they1 report, “[b]oth male and female flies showed a significant age-dependent increase in the number of flies exhibiting blue dye throughout the body after feeding.” The researchers named these blue flies Smurfs. Although the blue dye itself had no effect on mortality, “all flies in the population exhibited the Smurf phenotype before death.”1 The presence of the blue dye throughout the body (indicating loss of intestinal barrier function) was found to be a predictor of age-onset mortality.

The authors found intestinal barrier dysfunction in Drosophila to be linked to a variety of markers of aging, including systemic metabolic dysfunction, increased expression of immunity-related genes, and reduced spontaneous physical activity.1

The “revenge” of the fly, mentioned above, would be manifest if the blue dye experiments were replicated in humans with similar results. In the meantime, the authors report that several age-related changes take place in the intestinal epithelium of rodents, including barrier dysfunction. Defects in intestinal barrier function have been associated in humans with intestinal or extraintestinal inflammatory disorders, multiple sclerosis, chronic heart failure, cancer, and Parkinson’s disease, as well as being a common event in critically ill patients.1 In a recent paper,3 researchers noted that increased intestinal permeability allowing the abnormal passage of substances from inside the intestines to enter the general circulation may be responsible for food allergies and even metabolic syndrome.

The researchers suggest that, on the basis of prior research, a key structure in maintaining the intestinal barrier is the tight junction lining the gut. In what the authors term a “leaky gut” dietary AGEs (advanced glycation endproducts) can enter the general circulation, where they induce inflammation3 and, hence, may contribute to diseases such as diabetes and cardiovascular disease. These authors suggest supplementation with the amino acid glutamine, which is an important nutrient for preventing increased intestinal permeability (four papers are cited in support), and possibly curcumin because of its effects in reducing colonic inflammation and experimental colitis in animal models.

Interestingly, “intestines from aged flies contain higher counts of indigenous bacteria than their younger counterparts and this has been reported to influence epithelium renewal during aging.”1


  1. Rera et al. Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Nat Acad Sci USA. 109(52):21528-33 (2012).
  2. Elie Metchnikoff. The Prolongation of Life (G. P. Putnam’s Sons, 1908) We have an original copy of this book. They are available remarkably inexpensively from sellers of antiquarian books (or were as of several years ago) if you would like a copy yourself. It is also available from Amazon.com as a reprint.
  3. Rapin and Wiernsperger. Possible links between intestinal permeability and food processing: a potential therapeutic niche for glutamine. Clinics. 65(6):635-43 (2010) This is an Open Access article. doi: 10.1590/S1807-59322010000600012

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