Sci. Aging Knowl. Environ., 24 November 2004
Vol. 2004, Issue 47, p. nf105
[DOI: 10.1126/sageke.2004.47.nf105]


Young at Heart

Life-extending mutation preserves fly hearts

R. John Davenport

Slowing the aging clock keeps the heart ticking strong, according to new work in flies. Insects with a life-stretching genetic alteration maintain robust heart rates and withstand cardiac stress better than do normal insects. The work shows that a mechanism that stalls aging in the entire organism also hinders deterioration of particular tissues.

Mutations in insulin-related signaling pathways extend the lives of numerous creatures, including fruit flies, nematodes, and mice (see "One for All"). But researchers aren't sure how snafus in these circuits influence the decline of specific tissues. For instance, heart tissue weakens as animals age, but no one knows whether longevity signals maintain that organ's vigor. In the new work, Wessells and colleagues investigated whether life-prolonging defects in insulin-related signaling genes obstruct the heart's slide.

To assess cardiac health in aging flies, the researchers measured heart rate and response to stress. In normal flies, heart rate slowed as insects got old. The team then stressed the animals' hearts by applying electrodes that forced them to beat faster and determined how frequently the organs failed. Hearts of older flies were more likely to stop or beat erratically than were those of younger ones. The increase in failure rate with age gradually tapered off in the oldest flies, the same pattern seen in fly death rates. That similarity suggests that fly aging influences the deterioration of heart tissue.

Next, the team measured the same characteristics in long-lived flies with glitches in the insulin-like signaling pathway. Elderly flies with mutations in the insulin-like receptor protein throughout their bodies suffered heart failure at the same rate as did young, normal flies, and their hearts beat at a healthy pace. Next, the team tinkered with insulin-like signals in the heart alone. First, they cranked up the pathway by augmenting receptor production in cardiac cells. The organs beat slower and failed more often than normal, although these measures didn't significantly worsen with age. The team then shut down insulin-like circuits in the heart by generating abundant quantities of a molecule that switches off a key pathway protein. In these flies, hearts withstood stress and beat rapidly well into old age. The organs also remained robust in flies engineered to generate extra quantities of FOXO, a protein that ramps up when insulin-like signals quiet. Together the findings indicate that stanching insulin-like signals in the heart staves off the effects of aging on that organ.

"This is absolutely a stellar, landmark paper," says cardiologist Jeanne Wei of the University of Arkansas for Medical Sciences in Little Rock. It's the first time that anyone has tied this longevity pathway to impairment of a specific organ, she says. Now, heart researchers should test whether similar pathways protect mammalian hearts, she says. The new ability to assess cardiac function in the fly gives researchers an important new tool for understanding how the organ changes with age, says cardiologist Jay Edelberg of Weill Medical College of Cornell University in New York City. Deciphering the mechanisms by which blunted insulin-like signals protect tickers might reveal new ways to help human hearts keep pace.

November 24, 2004
  1. R. J. Wessells, E. Fitzgerald, J. R. Cypser, M. Tatar, R. Bodmer, Insulin regulation of heart function in aging fruit flies. Nat. Genet., 22 November 2004 [e-pub ahead of print]. [Abstract/Full Text]
Citation: R. J. Davenport, Young at Heart. Sci. Aging Knowl. Environ. 2004 (47), nf105 (2004).

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