This (1) is what I have come to term "the usual nonsense." The text states that "Mice carrying the EFmKL46 or EFmKL48 transgenic alleles, fed ad libitum, outlived wild-type controls by 20.0 and 30.8%, respectively, in males and by 18.8 and 19.0%, respectively, in females." Specifically, "The averagelife span of male wild-type, EFmKL46, and EFmKL48 mice was 715 ± 44 days,858 ±40 days and 936 ± 47days (means ±SEM), respectively. The average life span of female wild-type, EFmKL46, and EFmKL48 mice was 697 ± 45 days, 829 ± 32 days and 830± 29 days, respectively."
However, there was only a MEAN LS "extension" in either strain, and the "extension" only constituted an
incomplete NORMALIZATION of the shortened LS of the animals in question. The control strain in this experiment was C3H, which is a short-lived strain of mouse; see mortality and pathology info here:
http://www.informati.../docs/C3H.shtml A normal, healthy, non-genetically-fucked-up mouse should on average live ~900 d, and ~1200 max (2); these animals clearly do not constitute healthy controls, tho' Kuro-o's group seem to have done an unusually good job of raising them, to their credit. IAC, one can normalize the survivorship of such animals by simply interfering with the built-in disease vulnerability that cuts short their lives. This tells us nothing at all about aging, and in no way helps us to develop anti-aging interventions for humans.
They don't formally report max LS (tenth-decile survivorship), but eyeballing the curves (Fig 1, A & B) shows that the last mouse in each group died at the age of roughly:
Wild-type C3H males:990 days
Wild-type C3H females: 1010 days
EFmKL46 transgenic males: 1110 days
EFmKL48 transgenic males: 1160 d
EFmKL46 transgenic females: 1080 d
EFmKL48 transgenic females: 1080 d
All that the extra klotho dose did was move the 2 transgenics closer to -- and in no case fully! -- the average and maximum lifespan expected of mice that aren't genetically disfavored or in poor husbandry conditions. In the case of the females, the effect is nearly negligible; since the data were never formally reported, I'm guessing that the difference was statistically nonsignificant, as I suggest it was also "clinically" and scientifically.
Of course, a zillion things -- melatonin, cysteine, hydroxylamine, alpha-tocopherol, ethoxyquin, 2-mercaptoethylamine, etc etc -- do this. This tells us something about how antioxidants can counter the abuse of poor animal husbandry or bad genes, but it doesn't tell us anything about basically healthy animals -- and even less about aging per se.
It's really too bad that they didn't do this on a longevous background, not only because it would have given meaningful results in general, but light of recent surprising data suggesting that it is the low levels of thyroid hormones, and not IGF1, that slows aging in dwarf rodents (3,4); other GH/IGF1 or insulin signaling disruptions have not been clearly demonstrated to slow down aging (8). A clearer result, positive or negative, with klotho as an IGF1/insulin signal disrupter would have added significantly to our understanding.
IAC, this was not going to lead to a truly
useful result, as Aubrey de Grey has ably shown (5-7), attempting to "clean up" the deleterious effects of normal metabolism is an ineffective strategy for the development of anti-aging biomedicine: what is needed is interventions which directly target aging damage per se.
-Michael
1. Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-O M.
Suppression of Aging in Mice by the Hormone Klotho.
Science. 2005 Aug 25; [Epub ahead of print]
PMID: 16123266 [PubMed - as supplied by publisher]
2. Miller RA, Harper JM, Dysko RC, Durkee SJ, Austad SN.
Longer life spans and delayed maturation in wild-derived mice.
Exp Biol Med (Maywood). 2002 Jul;227(7):500-8.
PMID: 12094015
3. Vergara M, Smith-Wheelock M, Harper JM, Sigler R, Miller RA.
Hormone-treated snell dwarf mice regain fertility but remain long lived and disease resistant.
J Gerontol A Biol Sci Med Sci. 2004 Dec;59(12):1244-50.
PMID: 15699523 [PubMed - indexed for MEDLINE]
4. Sonntag WE, Carter CS, Ikeno Y, Ekenstedt K, Carlson CS, Loeser RF,
Chakrabarty S, Lee S, Bennett C, Ingram R, Moore T, Ramsey M.
Adult-onset growth hormone and insulin-like growth factor I deficiency reduces neoplastic disease, modifies age-related pathology, and increases life span.
Endocrinology. 2005 Jul;146(7):2920-32. Epub 2005 Mar 24.
PMID: 15790724 [PubMed - indexed for MEDLINE]
5. de Grey AD.
An engineer's approach to the development of real anti-aging medicine.
Sci Aging Knowledge Environ. 2003 Jan 8;2003(1):VP1. Review.
PMID: 12844502 [PubMed - indexed for MEDLINE]
http://www.gen.cam.a...ens/focusPP.pdf6. de Grey AD.
Challenging but essential targets for genuine anti-ageing drugs.
Expert Opin Ther Targets. 2003 Feb;7(1):1-5.
PMID: 12556198 [PubMed - as supplied by publisher]
http://www.gen.cam.a...sens/manu21.pdf7. de Grey AD, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJ, Stock G.
Time to talk SENS: critiquing the immutability of human aging.
Ann N Y Acad Sci. 2002 Apr;959:452-62; discussion 463-5.
PMID: 11976218 [PubMed - indexed for MEDLINE]
http://www.gen.cam.a...sens/manu12.pdf 8. Barger JL, Walford RL, Weindruch R.
The retardation of aging by caloric restriction: its significance in the transgenic era.
Exp Gerontol. 2003 Nov-Dec;38(11-12):1343-51. Review.
PMID: 14698815 [PubMed - indexed for MEDLINE]