Subject: Sci.life-extension FAQ #3: The FAQs

From: [email-masked] (Brian Manning Delaney)
Date: Wed, 9 Mar 1994 14:51:50 GMT

(Sci.life-extension FAQ #3.)           January 27, 1994 Edition.

                  Some Frequently Answered Questions

(Note: I don't cover all of the different topics that have come up in
Sci.life-extension in this FAQ, only a few things that come up
frequently. I don't have the time for a more thorough review. Most
life extension techniques are covered better in the publications
listed in the Resources FAQ; there's no point in duplicating that
info. -Brian.)

[] Contents.
  1. What is life extension?
  2. How do I slow down the aging process?
    -> Calorie restriction.
    -> Anti-oxidants.
   2a. Why does maximum life span matter and not average life span?
    -> Chromium.
    -> Deprenyl.
    -> Altering Metabolism.
    -> Hormones.
    -> Thoughts on Melatonin Supplementation.
    -> Others.
  3. How does exercise affect longevity?
  4. How can I get by with less sleep?
  5. Who would want to live forever?
  6. Well, why would anyone want to live more than a normal life span?
  7. What about the social consequences?

1. What is life extension?

Life extension is the attempt to live longer, and to "live younger,"
that is, to be more youthful while alive.

2. How do I slow down the aging process?

Many methods of slowing down or reversing aging have been proposed,
but none is without controversy:

-> Calorie Restriction.

See the CR FAQ (Sci.life-extension FAQ #4) for details.

-> Anti-oxidants.

Many people believe that consuming anti-oxidants will slow down aging.
There are, indeed, studies that show that certain anti-oxidants will
increase maximum life span (though most of the studies dealing with
the effects of anti-oxidants on life span measure _average_ life
span). However, none of these studies, to the best of my knowledge,
controlled for caloric-intake, so the effect may just be CR (e.g.,
consuming anti-oxidants may just change one's appetite). In my view
the jury is still out, though anti-oxidants look promising.

There is growing evidence, however, that many anti-oxidants protect
against cancer and heart-disease, whether or not they also affect aging.

(There may eventually be an anti-oxidant FAQ.)

2a. Why does maximum life span matter and not average life span?

If a study shows that average life span is increased when a drug or
supplement is consumed, the increase could just be the result of
disease-prevention, not of a modulation of the aging process. If the
disease prevented is not something for which you are at risk, there is
no reason to take the drug or supplement.

But if members of the group taking the drug or supplement live longer
than the longest-lived, non-diseased members of the control group,
then it's much safer to conclude that aging has been affected in the
study group.

 -> Chromium.

There is some evidence that Cr supplements (chromium picolinate -- and
maybe chromium polynicotinate) increase the longevity of rodents.
There has been some criticism of the (very few) studies done so far --
perhaps the Rat Chow (yes, that's the name of the grub sold to labs)
used for the control groups was low in Cr, for ex., or high in simple
sugars. Extra Cr is excreted from the body w/no probs though, so it
seems worth it to try it.

-> Deprenyl.

Deprenyl (Eldepryl) is a drug available by prescription in the U.S.
used mostly to treat Parkinson's Disease. However, some studies have
shown that it increases maximum life span by 30%. One study attempted
to control for Calorie restriction, so it appears that the effect is
not secondary to CR [1]. The person (the only person so far,
suspiciously), researching and advocating deprenyl as an anti-aging
drug recommends starting the drug at the age of forty-five or so for
its anti-aging effects, not sooner.  (It is supposed that the drug
works by off-setting various changes that don't take place to a
significant degree before the age of forty-five [2].)

A report by a second research group recently confirmed the finding
that deprenyl is "life-extending", though the results weren't quite as
good as those seen in the previous studies.

-> Altering Metabolism.

There is reason to believe that slowing down, or increasing the
efficiency of, metabolism may slow down aging. This may, in fact, be
the means by which CR produces its dramatic effects on longevity [3].
If slowing metabolism would slow aging, then meditation, for example,
would have an anti-aging effect.

Robert Bradbury ([email-masked]) contributed the
following on the relation between stress and aging:

  Ongoing stress raises the circulating glucocorticoid levels in the
  body.  Glucocorticods tell a number of cells to reduce their glucose
  consumption (because your muscles need that glucose to run from
  dangerous coworkers :-)).  There are 3 possible ways this may impact
  the aging process:

  1) Higher circulating levels of glucose may caused increased protein
     glycation leading to accelarted aging (esp. heart disease) as
     found in diabetics who also have problems controlling glucose levels.
  2) Higher GC levels turn off the immune system (a major consumer of
     energy (5+%?)) because it is "non-essential".  Decreased immune
     system activity can lead to increased bacterial/viral infection
     rates. [Furthermore, some theories of aging hold that alterations
     in immunity are the primary events leading to aging. -BD.]
  3) The portions of the brain involved in glucocorticoid stimulation
     [the hippocampus] have very high levels of GC receptors to
     act in a negative feedback control of GC levels.  Unfortunately
     these GC receptors which tell cells to decrease GC production may
     also cause decreased glucose intake making them more vulnerable
     to insults (low O2, other stresses) which lead to an increased
     rate of cell death [and a decreased abillity to inhibit the
     release of GC].  Eventually the cell death causes a failure
     of the GC system and/or other brain pathologies found in aging.
     (Robert Sapolsky is the person who developed this theory.)

[Sapolsky's book, "Stress, the Aging Brain, and the Mechanism of
Neuron Death," is a quick, fun, not too terribly technical read.]

 -> Hormones.

Here's an article I wrote on growth hormone and melatonin.

In article <[email-masked]> [email-masked] (Bill Baker) writes:
>Does anyone know about the potential rejuveantion properties of this
>hormone?  I seem to remember reading about a study a couple of years 
>ago that was done on men over 55 or so, where after taking this, many
>indicators of aging, immune system function, lean muscle mass to fat,
>general energy level, and sexual desire increased to levels that they 
>had many years ago.  This happened during  the study, while the men were
>on it, I don't think the effects continued after.

Right, the effects did not continue w/discontinuation of the hormone.

If you order events leading to or causing aging from central or
originating to derivative, I think declining GH levels would be near
the derivative end of the scale. Indeed, as another poster mentioned,
not all aging men (don't know about women) have low GH levels, so low
GH is certainly not universally essential for aging.

If anyone's considering hormone-replacement, it may be wiser to choose
a hormone closer to the "central" end of the spectrum of causes of
aging. Melatonin, for example, may be such a hormone.

Note: this is 60-70% guesswork, since so little research has been
done. But some research with rodents indicates that melatonin
replacement has a more long-lasting and global effect on various
parameters of aging, whereas GH therapy seems to influence more
"superficial" aspects of aging (things you could achieve in part by
lifting weights, for example). (See below for more on melatonin.)

>Any FAQ's on this issue in particular or any other sources that you
>folks might know of to get more info. on this??
>Any ideas on dosages used, possible adverse effects,
>and means of getting some by prescription or
>otherwise, if you have taken 
>some, or even if you think it's complete crap, let's have a dicsussion
>on this forum.
>Thanks for any responses in advance.

There are plenty of articles on melatonin that you could find easily
in a medical library (just look in recent gerontology and
neuroendocrinology journals).

-Brian.

 -> Thoughts on Melatonin Supplementation.

I'd say a (highly) conservative approach to melatonin-chomping would
be to go to a sleep lab to get your nocturnal melatonin levels
measured, take an amount of melatonin that would seem to correct any
"problems" (to bring the levels up to those of a healthy person in
his/her early twenties), get measured again to see if further
adjustments are necessary, and then go back and repeat the whole thing
every few years.

But that's kind of a pain. You might be able to measure the levels on
your own (metabolites in urine), but it could be unreliable.

Hormone-replacement therapy as an anti-aging strategy is tricky
business. Another approach would be to say "Well, the rodents in
several studies consumed it and they lived longer, even though they
probably had their levels brought up higher than the levels of young,
healthy rodents, so I'll just take a large amount and assume it'll
make me live longer."

This is in keeping with the idea that its primary effects are on free
radicals, so we should just get a bunch of it in our blood, period
(since nixing free rads. to the greatest degree practically possible
is a good thing, so this reasoning would go).

Note, however, that a few studies w/supplemental melatonin resulted in
_decreased_ life spans. These were studies where the melatonin was not
administered nocturnally, which I suspect was the problem.
Nevertheless, it's important not be swayed by pop literature calling
melatonin a "fountain of youth." It's not that simple. Another
interesting twist: in some studies with hamsters, pinealectomized
animals (animals with the principle source of exogenous melatonin
removed) lived (slightly) _longer_ than controls [3.5].

We don't yet know all of the effects supplemental melatonin may
have on humans.

-> Others.

There are many other substances that are purported to have an effect
on aging, including the hormone DHEA, thymic extracts, and more.
Walford reviews many of these in _120-Year Diet_. The Life Magazine
article cited in the Resources FAQ (Sci.life-extension FAQ #2) covers
many of these drugs and treatments also, though not in detail. The
newsletters I mentioned usually have updates on new anti-aging drugs
or new research into already existing drugs.

3. How does exercise affect longevity?

Exercise improves health in a variety of ways, making it less likely
that fatal diseases will strike. However, the relation between
exercise and the rate of aging per se is complicated. In a fascinating
study by John Holloszy, exercise increased the maximum life spans of
rodents not on Calorie restriction, but decreased the life spans of
the rodents that were on CR [4]. A more recent study by Holloszy
showed that the picture might be a bit more complicated: exercise
increased the average but not maximum life span of non-CR rodents,
whereas exercise did not reduce the maximum life span of the CR
rodents, but it did have a deleterious effect on the "weaker" rodents
(it reduced the average) [5].

Walford recommends moderate exercise: a little aerobic exercise a few
times a week, and a little resistance training (weight lifting, for
example) to strengthen bones.

Ely Rabani <[email-masked]> wrote a nice article that can be
perused in the archives. Briefly, the idea was that exercise produces
free radicals (not too surprising, since we know that energy
utilization increases during exercise...). Experiments with radon gas
show that free rads. promote scavenging activity in the body. [Ely
said a study showed that rodents exposed to Rn lived _longer_ in one
study.]  Perhaps the same thing might happen with exercise. This might
explain why exercise helps rodents live longer if they aren't doing
CR, but may not help if they are doing CR, since under CR, perhaps,
fewer free radicals are being produced, so the effect of exercise may
be irrelevant. (Or, under CR, free rad-scavenging is stepped-up --
this all just guesswork, here, of course.)

4. How can I get by with less sleep?

If you're depressed, getting un-depressed would help a great deal.
Also, there are many non-psychiatric medical problems that can result
in fatigue and an increased need for sleep. If you suffer from unusual
fatigue or need for sleep it might be a good idea to see a doctor.

As for "life extension" drugs that might reduce the need for sleep,
many people report that DMAE (dimethylaminoethanol) reduces their need
for sleep. DMAE has been shown to increase R.E.M. sleep as a
percentage of total sleep, which may mean that people on DMAE need
less sleep altogether. (DMAE is a precursor to a neurotransmitter,
acetylcholine.  It may be that that DMAE exerts its effects on
sleep-needs by increasing brain-levels of acetylcholine.)
Centrophenoxine (aka, Lucidril, meclofenoxate), which is essentially
DMAE linked to another molecule, appears to have similar (though not
quite the same) effects as those of DMAE.

There are side-effects, however. Taking too high an initial dose of
DMAE or centrophenoxine can cause muscle twitches or cramping. This
effect is temporary, though it _may_ be that taking an inital dose
that is _way_ too high can produce permanent dyskinesia. (There have
been isolated reports of this, but it's not clear what caused the
dyskinesia.) Even if the risk is minimal, proceed with caution.

Note: some people report that DMAE makes them depressed.

DMAE is currently available over-the-counter in the U.S.

Piracetam has also been shown to increase R.E.M. sleep. It has
virtually no side-effects, but it is not available in the U.S. at this
time [6].

5. Who would want to live forever?

Most people interested in life extension don't want to live forever.
And the people who do believe that they would never run out of things
to do.

6. Well, why would anyone want to live more than a normal life span?

There are many reasons, some of them "healthy," some, perhaps, not.
Some people want more time to fulfill their dreams, some people are
depressed and look to the far future as a time where potential
redemption may be possible, etc., etc. Some people are just curious
about what the 22nd century will look like.

7. What about the social consequences?

(Note: this sort of question -- as well as the preceding two -- are
not questions that belong in this group, however interesting they might
be. Perhaps someone could start talk.life-extension....)

It's easy to imagine both negative and positive social consequences.
Over-population might be a consequence of extended life span (though
one could easily imagine the desire to have children being radically
reduced with increased longevity), and racial and class balances might
be upset if only wealthy individuals have access to life-extending
technology.

On the other hand, responsibility for the environment and society
might be increased if people know that they won't be dead before the
consequences of their actions manifest themselves.

-------------------------------------------------------

By the end of the summer I should have a section of this FAQ dealing
with some of the technical discussions that have occurred over the
last few months -- whether the Hayflick limit would is more relevant
to human aging than changing rates of, or effectiveness of, protein
repair, etc. I don't have time now. For now, you can always check the
archived articles (see the Resources FAQ for ways of getting the old
articles) for details.

[9/15: Well, looks like the technical summary will have to wait some
more.]

[1/94: Now it looks like it will never happen. Sorry. I'm too busy. If
anyone wants to volunteer, that would be great.]

Email me with suggestions for future editions of this FAQ (though this
may be the last edition by me).

Pardon the rough editing,
Brian <[email-masked]>

Notes:

[1] 12. Kitani K; Kanai S; Sato Y; Ohta M; Ivy GO; Carrillo MC.
Chronic treatment of (-)deprenyl prolongs the life span of male
Fischer 344 rats. Further evidence. Life Sciences, 1993, 52(3):281-8.

[2] Knoll J. (-)Deprenyl-medication: a strategy to modulate the
age-related decline of the striatal dopaminergic system. Journal of
the American Geriatrics Society, 1992 Aug, 40(8):839-47.

[3] Although a somewhat more likely explanation, in my view, would
involve the increase in the fraction of good proteins in cells (and in
cell membranes), and/or decreased glycation from lower glucose levels.
But this is a long story.

[3.5] Hoffman RA, et al "Growth and development of Golden Hamsters;
influence on the pineal gland, melatonin and photic output," in Brown
GM and Wainwright SD (eds): _The Pineal Gland, Endocrine Aspects,
Advances in the Bio-Sciences_, vol. 53, pp 289-293. (This book is
equivalent to: _Pineal Gland & its Endocrine Role: Proceedings of a
Symposium on the Pineal Gland Held in Canada, April '84_.) Look at the
articles cited in this one for additional info.

[4] Cited in Walford, _120-Year Diet_, p. 189-90.

[5] Holloszy JO. Exercise and food restriction in rats. Journal of
Nutrition, 1992 Mar, 122(3 Suppl):774-7.

[6] Wetzel W. Effect of repeated application of nootropic drugs on sleep
in rats. Biomed-Biochim-Acta. 1990; 49(5): 405-11.
-- 
Brian M. Delaney <[email-masked]>
              or <[email-masked]>