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[A1CR]

At first, from the introduction to a new paper by (1) and
the abstract of
the paper to which it refers (2) appeared to examine
longevity with respect to a cancer connection. However, it
appeared to
present findings with respect to CR as well. Worms people
are not, but they
may suffice if their genetic model systems are available,
until better
strategies may draw direct implications for mammals,
including humans.

1. Science 313 (5789) 18 Aug 2006: 888

Aging and Cancer

Is there a link between organismal aging and cancer?
Pinkston et al.
(p. 971) address this question in a worm model of aging and
tumor
development and find that different signaling pathways
implicated in the
aging process also control tumorigenesis. Mutant worms with
long life spans
appear immune to the life-shortening effects of tumors
because of enhanced
defense mechanisms, including increased apoptosis and
decreased cell
proliferation within the tumors. Signaling pathways that
control longevity
may have coevolved with tumor suppressive mechanisms.

2. Mutations That Increase the Life Span of C. elegans
Inhibit Tumor Growth
Julie M. Pinkston, Delia Garigan, Malene Hansen, and Cynthia
Kenyon

Science 313 (5789) 18 Aug 2006: 971-975.

Journal comments: A strain of worm that develops
cancer as it ages is
protected from tumor growth by mutations that extend its
life span.

... gld-1 ... a wide variety of mutations that extend
C. elegans' life
span confer resistance to these tumors. The long life spans of
daf-2/insulin-receptor mutants were not shortened at all by
gld-1 mutations;
we attribute this finding to decreased cell division and
increased
DAF-16/p53-dependent apoptosis within the tumors. Mutations
that increase
life span by restricting food intake or inhibiting
respiration did not
affect apoptosis but reduced tumor cell division.
Unexpectedly, none of
these longevity mutations affected mitosis in normal
germlines; this finding
suggests that cellular changes that lead to longevity
preferentially
antagonize tumor cell growth.

....

Caloric restriction inhibits tumorigenesis in mammals,
and our findings
suggest that inhibiting the mammalian orthologs of isp-1 and
clk-1 may do so
as well. isp-1 mutations are thought to increase life span
by inhibiting
respiration (3, 4, 10). Perhaps tumor cells, which have low
rates of
respiration, are particularly sensitive to further
reductions, or perhaps
reducing respiration rates in surrounding cells inhibits
tumor growth. The
mechanism by which clk-1 mutations increase life span is not
known. C.
elegans clk-1 mutants, which receive essential quinones from
the environment
(27), do not have reduced metabolic output (28). The
longevity of clk-1+/-
mice has been associated with increased stress resistance
(2). ... many C.
elegans longevity mutations are tumor protective. The
generality of our
findings, along with the cancer resistance of long-lived
calorically
restricted and endocrine-mutant rodents, argues that
mutations such as the
p53 alleles that inhibit tumors but accelerate aging (12)
may be the
exception rather than the rule. It may be that during
evolution, longevity
and delayed tumorigenesis arose together-for example, from
endocrine pathway
and mitochondrial mutations that influenced both processes...