Creatine as an anti-aging supplement?

[David]

Biochim Biophys Acta. 2008 Jan;1780(1):16-26. Epub 2007 Oct 5

Differential effect of creatine on oxidatively-injured
mitochondrial and nuclear DNA.

Guidi C, Potenza L, Sestili P, Martinelli C, Guescini M, Stocchi
L, Zeppa S, Polidori E, Annibalini G, Stocchi V.

Creatine is a naturally occurring compound obtained in humans from
endogenous production and consumption through the diet. It is used as
an ergogenic aid to improve exercise performance and increase fat-free
mass. Lately, creatine's positive therapeutic benefits in various
oxidative stress-associated diseases have been reported in literature
and, more recently, creatine has also been shown to exert direct
antioxidant effects. Oxidatively-challenged DNA was analysed to show
possible protective effects of creatine. Acellular and cellular
studies were carried out. Acellular assays, performed using molecular
approaches, showed that creatine protects circular and linear DNA from
oxidative attacks. Nuclear and mitochondrial DNAs from oxidatively-
injured human umbilical vein endothelial cells were analyzed. Creatine
supplementation showed significant genoprotective activity on
mitochondrial DNA. This evidence suggests that creatine may play an
important role in mitochondrial genome stability in that it could
normalize mitochondrial mutagenesis and its functional consequences.
Thus, creatine supplementation could be used to prevent or ameliorate
diseases related to mitochondrial DNA mutations, and possibly to delay
aging.

PMID: 18022765

[Olafur Pall Olafsson]

Hi David,

One of the potential benefits of creatine that make it promising as an
anti-aging compound is the fact that, as opposed to many antioxidants,
it is actively taken up by mitochondria and therefore has the
potential to work as a mitochondrially targeted antioxidant. Here is a
quote from the full text article highlighting this fact:

"Cr might be a possible candidate as a mitochondrially-targeted
antioxidant, in that it is actively taken up by mitochondria through
specific transporters [43], unlike conventional antioxidants which
have limited efficacy due to the difficulty of accumulating within
these organelles."

Another interesting thing about creatine is that it appears to be able
to protect mitochondrial DNA against oxidative damage but not nuclear
DNA. Here is an quote from the full text the may explain why:

"The novelty of the present work is the finding that Cr protects
oxidatively-injured DNA, as shown by both acellular experiments and
cell based assays, respectively. In particular, our results show that
Cr supplementation significantly protects only mtDNA. That nDNA is not
sensitive to Cr-protection (Fig. 6, Fig. 7 and Fig. 8) is not
surprising. nDNA damage following oxidative stress is usually thought
to be a function of site-specific DNA-associated Fe-based Fenton
chemistry [69]. It is commonly assumed that iron is normally
associated with nDNA and many reports indicate that only iron-
chelators, unlike scavenging antioxidants such as Trolox [52] and [53]
(Fig. 9), are capable of protecting cells against oxidative nuclear
damage [53], [70], [71] and [72]. Importantly, Cr has been shown to
exert its antioxidant, cytoprotective activity via a scavenging
mechanism rather than through iron-chelation [17]: hence, the Cr lack
of protective effects on oxidatively-injured nDNA, as assayed with
QPCR, Real-Time PCR, 8-OHdG ELISA and fast halo assay, is not
surprising."

[David]

Thanks, Olafur. I certainly do miss having full-text access to all of
these articles like I did in grad school. In the mean time, I'll
continue taking my creatine monohydrate!
-David

[timo...@my-deja.com]

That's not surprising ATP is essential for most DNA repair activities.
NAD+ is only esse3ntial for PARP-1.