cron-web.org

[A1CR]

There appears to be a "beneficial role of
http://en.wikipedia.org/wiki/Insulin-like_growth_factor-1
[IGF-1] in
aging-induced cardiac contractile dysfunction". Previously,
evidence
sugggested, in the (1) paper, that "dietary restriction ...
leads to further
increases in insulin sensitivity and longevity in Ames
dwarfs".

1. Bartke A, Masternak MM, Al-Regaiey KA, Bonkowski MS.
Effects of dietary restriction on the expression of
insulin-signaling-related genes in long-lived mutant mice.
Interdiscip Top Gerontol. 2007;35:69-82.
PMID: 17063033

"dietary restriction ... leads to further increases in
insulin sensitivity
and longevity in Ames dwarfs"

2. Am J Physiol Heart Circ Physiol. 2006 Nov 3; [Epub ahead
of print]
Cardiac Specific Overexpression of Insulin-Like Growth
Factor-1 (IGF-1)
Attenuates Aging-Associated Cardiac Diastolic Contractile
Dysfunction and
Protein Damage.Li Q, Wu S, Li SY, Lopez FL, Du M, Kajstura
J, Anversa P, Ren
J.
PMID: 17085535

Aging is associated with hepatic growth hormone resistance
resulting in a
fall in serum insulin-like growth factor-1 (IGF-1) level.
However, whether
loss of IGF-1 contributes to cardiac aging is unclear. This
study was
designed to examine the effect of cardiac overexpression of
IGF-1 on
cardiomyocyte contractile function in young (3 mo) and old
(26-28 mo) mice.
Cardiomyocyte contractile function was evaluated including
peak shortening
(PS), time-to-90% PS, time-to-90% relengthening (TR90) and
maximal velocity
of shortening/relengthening (+/- dL/dt). Levels of advanced
glycation
endproduct (AGE), protein carbonyl, sarco(endo)plasmic
reticulum
Ca(2+)-ATPase (SERCA2a), phospholamban (PLB) and
Na(+)-Ca(2+) exchanger
(NCX) were assessed by Western blot. SERCA activity was
measured by
(45)Ca(2+) uptake. Aging induced a decline in plasma IGF-1
levels. Aged
cells exhibited depressed +/- dL/dt, prolonged TR90 and a
steeper PS decline
in response to increasing stimulus frequency compared with
young myocytes.
IGF-1 transgene alleviated aging-induced loss in plasma
IGF-1 and
aging-induced mechanical defects with little effect in young
mice. The
beneficial effect of IGF-1 transgene on aging-associated
cardiomyocyte
contractile dysfunction was somewhat mimicked by short-term
in vitro
treatment of recombinant IGF-1 (500 nM). AGE and protein
carbonyl levels
were higher in aged mice which were not affected by IGF-1.
Expression of
SERCA2a (but not NCX and PLB) and SERCA activity were
reduced with aging,
which was ablated by the IGF-1 transgene. Collectively, our
data suggest
beneficial role of IGF-1 in aging-induced cardiac
contractile dysfunction,
possibly related to improved Ca(2+) uptake.