Young Again? Controversial studies claim that two supplements reenergize aged rats (Oxidative damage; Nutritional supplements)
Authors: Leslie Mitch 
Published: August 2003

Your neighborhood health food store might already stock a cheap, safe antiaging tonic, say researchers who found that a pair of common supplements sharpens memory, boosts activity, and tunes up the energy-producing mitochondria in elderly rats. Although one company is charging ahead with human trials of the combination, some scientists dispute the key findings.

Most researchers agree that we can blame many of aging's travails on damaged mitochondria. Like a kiln that cracks from its own heat, mitochondria take a beating from the oxidants spawned when they burn food (see
"The Two Faces of Oxygen"
). Compared with healthy cells, cells with injured mitochondria use less oxygen and therefore produce less adenosine triphosphate (ATP). This energy shortage undercuts their ability to make repairs, detoxify nasties, and perform other crucial tasks, according to biochemist Bruce Ames of the University of California, Berkeley.

Ames and colleagues tested whether two popular supplements, acetyl-L-carnitine and α-lipoic acid--purported to boost energy and neutralize oxidants, respectively--could shield mitochondria and pep up aging animals. The researchers put old rats on a diet rich in both compounds for 2 to 7 weeks and then used a variety of tests to evaluate metabolism, mitochondrial efficiency, physical activity, and memory. For example, cameras monitored the rodents' scurryings. Biochemical analyses gauged mitochondrial membrane potential--an indicator of the organelles' energy-producing capacity--and oxygen consumption in liver cells, as well as amounts of oxidants and antioxidants.
Lethargic old rats that ate the supplement combo perked up physically, mentally, and biochemically, the researchers report in three papers. The rodents spent more than twice as much time prowling their cages as did other rats their age. They showed increased membrane potential and elevated oxygen consumption. Antioxidant concentrations rose and oxidant concentrations declined. The supplement takers also improved on the memory tests. The results show that the compounds provide short-term benefits to the animals, says co-author Tory Hagen of Oregon State University in Corvallis, but "we don't know anything about the effects on humans."
We might soon, because a company called Juvenon, which Ames and Hagen helped found, has completed a preliminary human trial of the supplements, aimed at finding an effective dose. Ames says that the results haven't been analyzed, but he is bullish on the prospects for using these compounds and other supplements to counter aging: "I'm convinced that tuning up human metabolism is going to give us improvements in health."
Critics call the studies flawed. David Nicholls, an expert on mitochondrial function at the Buck Institute for Age Research in Novato, California, says that the researchers used unreliable techniques to assess membrane potential and oxidant concentrations. The measurements of membrane potential in old rats are impossible, he says. Cells with such low values would die because they couldn't make ATP. Molecular biologist Simon Melov, also at the Buck Institute, echoes the criticism, adding that measurements of activity don't necessarily indicate greater vigor: Although the supplement-snarfing rats moved around more, they also spent more time resting, he notes.
Hagen defends the results, saying that in earlier work, the researchers validated the membrane potential technique with a different method. Ames is already preparing to test whether the compounds extend the lives of middle-aged rats.
--Mitch Leslie

T. M. Hagen, J. Liu, J. Lykkesfeldt, C. M. Wehr, R. T. Ingersoll, V. Vinarsky, J. C. Bartholomew, B. N. Ames, Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress.
Proc. Natl. Acad. Sci. U.S.A.
99
, 1870-1875 (2002).
[Abstract]
[Full Text]

J. Liu, D. W. Killilea, B. N. Ames, Age-associated mitochondrial oxidative decay: Improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L-carnitine and/or
R
-α-lipoic acid.
Proc. Natl. Acad. Sci. U.S.A.
99
, 1876-1881 (2002).
[Abstract]
[Full Text]

J. Liu, E. Head, A. M. Gharib, W. Yuan, R. T. Ingersoll, T. M. Hagen, C. W. Cotman, B. N. Ames, Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-L-carnitine and/or
R
-α-lipoic acid.
Proc. Natl. Acad. Sci. U.S.A.
99
, 2356-2361 (2002).
[Abstract]
[Full Text]