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The 34th Annual Meeting - AGING: Mechanisms and
Prevention
 It
is a great pleasure for us to invite you to participate
in the 34th American Aging Association Annual Meeting
which is scheduled to take place in Oakland, California,
June 3 - 6, 2005. In
keeping with the mission and the traditions of this
organization, the 2005 meeting will bring together those
actively engaged in experimental gerontological research
for the purpose of reviewing and discussing recent
progress, exchanging information, and relating research
in experimental animals to studies in the human.
The broad theme selected for the AGE 2005 meeting is
AGING: Mechanisms and Preventionn.
With this as a foundation, the meeting will consist of
oral and poster presentations of latest research in the
field and will further relate findings concerning
molecular and cellular mechanisms of aging to practical,
clinical issues. Topics and speakers were selected
with input of a Program Committee and will cover the
following topics:
-
genetic
and cellular mechanisms of aging,
-
role of
IGF-1 signaling,
-
caloric
restriction in the human,
-
genetics
of human longevity,
-
brain
aging and novel therapies for neurodegenerative
disease, and
-
use of
genomics and proteomics in gerontological research.
The program
will be arranged to ensure ample time for discussion and
audience participation (fifteen minutes after every
invited lecture). We believe that the program we
have developed is unique in its emphasis on mammals and
in its balance between the time devoted to basic
mechanisms and to research aimed at delaying or
preventing human aging and age-related disease.
This conference also provides an excellent learning and
mentoring opportunity for young investigators. They
represent the future of scientific advancement in
understanding the aging process. We hope to fund the
travel and lodging expenses of at least 15 graduate
students and post-doctoral trainees, and to provide for
the similar expenses of several minority group members.
Biomedical research is vital to the long-term objectives
of the health related industries. We are
encouraged that our allied industrial sectors, as well
as health-directed foundations recognize the importance
of aging research and participate in supporting
scientific meetings. We believe you will benefit from
participating in the conference, meeting leading
scientists in the field, and conversing with poster
presenters and others about your particular interests in
aging research.
We invite you to come and experience this meeting with
us as a speaker, poster presenter, attendee, exhibitor
or sponsor and join us in our mission to promote
research which will ultimately lead to a long, healthy,
productive life for all men and women.
Looking forward to welcoming you in California -
-
-
Andrzej Bartke,
PhD
-
Meeting Chair and President
-
American Aging Association
-
LINKS:
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Growth hormone signaling and longevity.
Why dwarf mice are long-lived and what does this
tell us?
Andrzej Bartke, Geriatrics Research,
Department of Medicine, Southern Illinois
University School of Medicine, P.O. Box 19628,
Springfield, Illinois 62794-9628,
USA, Email:
abartke@siumed.edu,
Telephone 217/545-7962, Fax 217/545-8006.
Hypopituitary dwarf mice, lacking growth hormone
(GH), prolactin and thyrotropin, and GH
resistant “Laron dwarf” mice live much longer
than their normal siblings (Brown-Borg et al.,
Nature 384:33, 1996; Flurkey et al., PNAS
8:6736, 2001,; Coschigano et al. Endocr
144:3799, 2003). Although these
observations were initially received with
considerable skepticism, evidence for extended
longevity of these animals is now undisputable
and evidence that aging is retarded in these
animals is very strong (Flurkey et al. PNAS
98:6736, 2001; Kinney et al. Horm. Behav.
39:277, 2001; Physiol. Behav. 72:653, 2001;
Ikeno et al., J. Gerontol. Biol. Sci. 58A:291,
2003, & unpublished). In Ames dwarf
(Prop1df), Snell dwarf (Pit1dw) and Laron dwarf
(GHR/GHBP-KO) mice, both the average and the
maximal life span is are significantly increased
with an occasional animal reaching an age of
over four years. This is a truly
remarkable age for a laboratory mouse living
under standard laboratory conditions with
constant access to high energy food.
Association of delayed aging with absence of GH
signaling raises a number of important questions
which are being addressed in current studies and
are likely to suggest directions for future
research.
First
of all, it is not understood how absence of GH
action leads to delayed aging and long life.
However, data available to date suggest a number
of possible mechanisms which singly or, more
likely, combined might account for the
“longevous phenotype” of Ames dwarf, Snell dwarf
and GHR-KO mice.
These
include (i) reduced circulating levels of IGF1,
and reduced somatic growth, (ii) reduced
secretion of insulin combined with enhanced
sensitivity to its actions, (iii) reduced body
temperature and generation of reactive oxygen
species (ROS) together with improved antioxidant
defenses, and (iv) increased cellular resistance
to multiple forms of stress. The
involvement and the suggested importance of
these mechanisms is supported by data obtained
in these and in other long-lived mutant mice
(reviewed in Bartke et al., J. Gerontol. Biol.
Sci. 56A, B340, 2001; Exper. Gerontol. 36:21,
2001), as well as by extrapolation of findings
obtained in genetically normal animals differing
in body size (Rollo, Evol. Dev. 55:55, 2002;
Miller et al. Aging Cell 1:22,2002), in normal
animals subjected to caloric restriction (Weindruch
& Sohal, N. Engl. J. Med. 337; 986:1997; Masoro,
Handbook Biol. Aging, Acad. Press 2001), and in
transgenic animals overexpressing GH (Bartke,
Neuroendocrinology 78:210, 2003). However,
it should be noted that evidence supporting
involvement of mechanisms listed above, although
substantial, is indirect being derived from the
studies of the association of various
physiological characteristics with aging and
life span.
In
addition to suggesting likely mechanisms linking
reduced GH and insulin signaling with longevity,
comparisons of long lived mutants to calorically
restricted (CR) animals reveal some interesting
and informative differences. For example,
adiposity is reduced in CR animals but increased
in GHR-KO mice (Bartke & Heiman, in press) while
Ames dwarfs exhibit relatively minor age-related
changes in adiposity (Heiman et al. Endocrine
20:149, 2003). This contrasts with the
situation in fat-specific insulin receptor knock
out (FIRKO) mice in which extension of life span
is associated with extreme leanness (Blüher et
al., Science 299:572, 2003). We suspect
that alterations in the secretory profile rather
than the mass of adipose tissue will prove
important in the control of aging, acting, most
likely, via alterations in insulin sensitivity.
Another important question raised by the
findings in dwarf mice is whether and if so, to
what extent the conclusions from studies in
these animals may apply to the human.
Delayed aging and long life of mice lacking GH
signaling is at odds with the ability of
injected GH to ameliorate some of the symptoms
of human aging and with the enthusiastic
promotion of GH, GH releasers, and various GH-related
products as “scientifically proven” means to
feel younger, look younger, and combat a host of
age-related problems. Moreover, GH
deficiency in the human is considered a risk
factor for cardiovascular disease, and reduced
life span was recently reported in a cohort of
genetically GH deficient individuals (Bessen et
al., JCEM 88:3664, 2003). However,
hypopituitary patients with a mutation
homologous to one of the life extending
mutations in the mouse are not short-lived and,
in fact, can reach a very advanced age (Krzisnik
et al., J. Endocr. Genetics 1:9, 1999).
Furthermore, ablation of the pituitary was
reported to reduce mortality of diabetic
patients, at least during the first 5-10 years
following irradiation (Klein et al., J. Diab.
Complic. 12:246, 1998). While more work is
clearly needed to resolve these controversies, I
believe that it is exceedingly unlikely that a
mechanism involved in the control of aging in
organisms ranging from worms to mice (and
probably operating also in unicellular yeast)
does not play a similar role in the human.
Extension of life by reducing IGF-1/insulin or
homologous signaling appears to represent an
ancient mechanism facilitating survival under
adverse conditions and promoting enhanced stress
resistance and repair capacity at the expense of
growth and reproduction when energy resources
are scarce (Tatar et al., Science 299:1346,
2003). In support of this reasoning,
enhanced sensitivity to insulin which
characterizes long lived dwarf and Laron dwarf
mice (Dominici et al., J. Endocr. 166:579, 2000;
173:81, 2002) was reported also in exceptionally
long-lived people (Paolisso et al., Am. J.
Physiol. 270:E890,1996).
However, the relative impact of reduced actions
of IGF-1 and/or insulin on life span will likely
prove to differ between species. For
example, reduced activity of the somatotropic
axis may be universally related to reduced risk
of neoplasia, but tumors are a much less common
cause of death in humans than in mice.
Conversely, IGF-1 may be protecting against
cardiovascular disease (Shut et al., Stroke
34:1623, 2003) which is a leading cause of death
in humans but not in mice. Moreover, in
comparison to other mammals, and particularly to
mammals of comparable body size, humans are
rather inordinately long-lived and therefore
there may be less “room for improvement” in the
human than in mice, flies or worms.
Ames,
Snell and Laron dwarf mice are clearly outside
the range of normal variation in body size,
longevity, and other characteristics of the
laboratory stocks of house mice. However,
the extreme features of these diminutive animals
offer exciting opportunities to discover and
elucidate physiological mechanisms that control
aging and longevity in genetically normal
individuals and likely apply broadly, including
our own species.
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