cron-web.org

[A1CR]

[posted on behalf of MR; 2001-07-30]

This 2001 article:

Kirk KL.
Dietary restriction and aging: comparative tests of evolutionary hypotheses.
J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):B123-9.
PMID: 11253149

http://biomed.gerontologyjournals.org/cgi/content/full/56/3/B123

... bears on several issues. First, the disposable soma theory (DST)
itself: the idea, accepted by nearly all evolutionary biologists
interested in aging, that evolutionary pressure selects organisms'
intrinsic lifespans based on extrinsic mortality -- that evolution
favors genetic profiles which give an organism JUST ENOUGH anti-aging
mechanisms (detox enzymes, endogenous antioxidants, phospholipase
activity, DNA repair capacity, or what have you) to get it thru' the LS
it will have in the course of its extrinsically-determined (by
predation, accident, etc) lifespan. To invest more resources in keeping
an organism biologically young longer is a waste of scarce resources, &
is thus selected against. Thus, biological aging rate is set by
environment -- like everything else. IF you accept the consensus view of
evolution, (I would actually add, "and even if you don't"), it's
actually logically impossible for this theory to be false. For more,
read Stephen Austad's excellent _Why We Age_, or the slightly inferior
_Time of Our Lives_ by Kirkwood.

By this theory, CR works because over the course of evolution, organisms
have repeatedly been exposed to food shortages. Under such
circumstances, the evolutionary fitness of organisms which continue on
following the usual evolutionary strategy -- BREED!! -- is greatly
reduced: they & their young BOTH end up starving to death too often as
the parent(s) invest in reproduction & childbearing/rearing. Those
organisms which instead respond by shutting down reproduction save
energy, and are more likely to survive to breed another day; while those
that invest a little extra energy in maintenance & repair, & which thus
ensure survival thru' famine AND being in good enough shape to breed
when food returns, will be more successful still. See, eg, (1).

Thus: to the degree that you reduce an animal's food supply, it will
proportionately increase investment in maintenance &repair (thus
slowing aging, preserving health & (if carried on long enough) extending
max LS -- ie. living longer than the animal would otherwise be designed
to be capable of doing) while reducing investment in reproduction
(cutting back on sex hormones, sperm production, &menstruation
(reproductive capacity) (2,3)). This extends lifespan -- including
reproductive lifespan, such that animals put on CR stop menstrual
cycling, but can be refed later &successfully breed after all thier
normally-fed cohorts are dead (4)!

(Indeed, heavy investment in reproduction can itself be
lifespan-shortening, as eg. as risk for reproductive-organ cancers is
increased the longer &higher one's sex hormone exposure is (as eg. for
early puberty) (5,6)).

Now, this theory has significant implications for several recent threads
-- most notably the "Necessary for CR?" thread and (as we shall see
when/if I get around to posting my 2 bits) the recent "PaleoMouse"
discussioin (ie is CR an artifact of the toxicity of lab chow relative
to the animals' natural diets, which is evaded thru' cutting back on the poison).

*Whew*! That was MUCH more premble than I'd intended!!

The new paper by Kirk et al is a big step forward. It looked at the
responses of assorted spp of rotifers to reduced food intake.
Essentially: "species that reduced reproduction when starved increased
their life spans under DR [as seen in the rodents], whereas species that
continued to reproduce when starved decreased their life spans under
DR."

From the abstract and/or full text:

================================

This study uses the comparative method to test evolutionary predictions
about the origin of the response to DR, using data from 10 species of
rotifers. Most species, but not all, responded to DR by increasing mean
life span, maximum life span, reproductive life span, mortality rate
doubling time [a direct measure of aging rate in a population], and
initial mortality rate.

Increases in mean life span ranged from 2–130%, and increases in maximum
life span ranged from 7–114%. Reproductive life span also increased in
most species, indicating that increases in longevity were not simply the
result of a longer prereproductive period. DR also increased MRDT in
most species for which data were available. Increases in MRDT ranged
from 16–147%.

Interspecific comparisons ... [provided] support for the idea that the
response to chronic DR is associated with changes in reproductive
allocation during short-term periods of starvation: species that reduced
reproduction when starved increased their life spans under DR, whereas
species that continued to reproduce when starved decreased their life
spans under DR.

There were exceptions to the general pattern of increasing life span and
MRDT under DR. Three species (B. plicatilis, K. testudo, and S.
pectinata) responded to DR by decreasing either life span, MRDT, or
both. Very low food levels, near or below R*, may result in
malnutrition. Thus, malnutrition may have contributed to the reductions
in mean life span for K. testudo. However, malnutrition cannot account
for the reductions in life span or MRDT for B. plicatilis or S.
pectinata. In these two species, life span or MRDT declined even as food
concentration declined from high to moderate levels.

To test the hypothesis that the response to chronic DR is associated
with the response to short-term episodes of starvation (12)(15), we need
to know how rotifers react to food deprivation. Kirk (18 ) tested the
response of nine species of rotifers to starvation. Animals were
deprived of food, beginning when they were young adults.

[T]he primary factor responsible for interspecific variation in
starvation time was whether or not the species curtailed reproduction
when starved. Species that reduced or eliminated egg production when
starved had relatively long starvation times, whereas species that
maintained egg production had shorter starvation times. Two species in
the genus Synchaeta increased reproductive rates when starved; these
species had very low starvation times (0.4–0.7 days) and effectively
reproduced themselves to death. Interspecific comparisons showed that
starvation time was negatively correlated with the rate of reproduction
during starvation (relative to fed controls). This is an example of an
interspecific trade-off between reproduction and survival. Such
trade-offs are often easiest to detect under stringent conditions such
as food shortage or starvation (33).

Data are available on the response to both starvation and chronic DR for
two rotifer species, B. calyciflorus and S. pectinata. When starved, B.
calyciflorus reduced its reproductive rate to 44% of that of fed
controls, whereas S. pectinata increased its reproductive rate to 160%
of that of fed controls (18 ). As predicted, the response to starvation
was associated with the response to chronic DR. B. calyciflorus, which
decreased its reproductive allocation when starved, increased its life
span and MRDT in response to DR (Fig. 3 and Table 1 ). In contrast, S.
pectinata, which increased its reproductive allocation when starved,
reduced its life span and MRDT in response to DR.

These data provide the first comparative evidence in support of the idea
that how species respond to starvation, particularly in terms of
reproductive allocation, can predict how species will respond to chronic
DR (12)(15).

There are additional differences in the way that B. calyciflorus and S.
pectinata respond to changes in food level. B. calyciflorus reduced the
size of
its eggs in response to chronic DR (34) and reduced its respiration rate
when starved (35). In contrast, S. pectinata did not change egg size or
respiration rate in response to DR or starvation. This provides further
evidence that the allocation patterns of S. pectinata are relatively inflexible.

Another way to explore the evolution of the antiaging action of DR is to
use theoretical modeling. Shanley and Kirkwood (44) formulated a dynamic
programming model that determined the optimal allocation of resources to
reproduction and somatic maintenance in mice fed various food levels.
The model predicted that, in environments where animals are subjected to
episodes of famine, optimal allocation to maintenance, and thus life
span, will increase under DR. This supports the hypothesis that the
response to chronic DR is an adaptation to life in environments with
variable food levels (12)(15).

==================================================

I hasten to add that I believe that the truly ADAPTIVE, response aspects
of CR are only part of the story -- that purely mechanical
inevitabilities (as eg less food = less total glucose exposure) do play
some role in CR (7) -- that processing Calories is, in itself,
intrinsically, toxic, &that CR bennies are thus to some extent
continuous across the entire range of Caloric intake (as was shown in
CR-responsive *AL* rodents by Ross (8 )). However, CR is IMHO PRIMARILY
an evolutionarily-driven response. If you AREN'T experiencing key
aspects of the response, subjectively (as eg. lower libido &or sex
hormones and/or sperm counts and/or amennorhea), then it is my educated
amateur's opinion that you probably aren't fully "in CR mode," and may
not be touching on aspects of the CR effect (as is in line with these
new data).

-MR

1: Masoro EJ, Austad SN.
The evolution of the antiaging action of dietary restriction: a hypothesis.
J Gerontol A Biol Sci Med Sci. 1996 Nov;51(6):B387-91.
PMID: 8914486

2. http://groups.yahoo.com/group/crsociety/message/6301

3. Young KA, Zirkin BR, Nelson RJ.
Testicular regression in response to food restriction and short
photoperiod in
white-footed mice (Peromyscus leucopus) is mediated by apoptosis.
Biol Reprod. 2000 Feb;62(2):347-54.
PMID: 10642572

4. Merry BJ, Holehan AM.
Onset of puberty and duration of fertility in rats fed a restricted diet.
J Reprod Fertil. 1979 Nov;57(2):253-9.
PMID: 513013

5. http://groups.yahoo.com/group/crsociety/message/6010

6. http://groups.yahoo.com/group/crsociety/message/5820
http://groups.yahoo.com/group/crsociety/message/5834

7. http://groups.yahoo.com/group/crscience/message/25 (Not hard evidence
-- just reasoning).

8. http://groups.yahoo.com/group/crsociety/message/6518

[A1CR]

[Posted on behalf of MR and Dean; 2001-08-01]

Dean wrote:
>
> MR wrote [paraphrase]:
> > [A review of a tremendously interesting paper about the tradeoff
> > between reproduction and maintenance in different species of
> > rotifers. It concluded that there really is such a
> > tradeoff - animals that shut down reproductive activities during
> > times of famine live longer than those that go right on (or
> > increase their rate of) procreation.
>
> One point of clarification. I somehow got the mistaken (and stupid)
> impression that rotifers were a kind of rodent. I think this misconception
> stemmed from this line from your post:
>
> > Essentially: "species that reduced reproduction when starved increased
> > their life spans under DR [as seen in the rodents], whereas
> > species that
> > continued to reproduce when starved decreased their life spans under
> > DR. [dietary restriction; CR by any other name]"
>
> Obviously, rotifers are not rodents

Correct; I didn't mean to imply that they were, though I can see how that
could be one reading of the above. What I meant is that rodents, when
starved, (a) reduce their reproduction (strictly: their capacity for
same, as vis oestrus, spermatogenesis, etc) and (b) increase their LS.
The news of this paper is not that those rotifers which do (a) do (b),
and those that don't do (a) don't do (B), so that a causal relationship
between (a) and (b) in rotifers seems very likely, and likewise a similar
relationship rodents (rather than the 2 facts being purely
coincidental).

-MR