Paul:

I read with interest your post to Russell Cheney, and at the very end
you made this very provocative statement:

[Finally, as I have told you for several years, the considered result
of all my research and reading tells me that you are overdoing your
running and will likely run yourself into an early grave if you
continue. --Paul]


Could you please elaborate on this and does your view extend to weight
lifting or any vigorous exercise in gereral?

Warmly,
Erich Brueschke

[The best way to begin my response is to remind you and other readers that
everything: a particular food, a supplement, radiation, heat, cold, oxygen,
water, even time! has either an inverted J or inverted U (both generally
stretched horizontally on their sides) shaped curve of benefit to the health of
the human body (on the y-axis) to dosage (on the x-axis). And whenever I say
"health" I include longevity as a part of time-integrated health. The general
rules for all things is that both too little and too much are detrimental to
human health. This has also been stated as: "The dose makes the poison".

[Many of the beneficial effects of exercise are due to a hormesis effect. The
term hormesis refers to the beneficial effects of low doses of otherwise harmful
substances. One example of this is the increase in reactive oxygen species (ROS)
generation during exercise, as the abstract below states. Exercise results in
increased ROS formation in the body. ROS, while generally having harmful
effects, if present in sufficient quantities can exert a beneficial adaptive
response in the body. But if they are not present in high enough quantities, or
on the other hand too high quantities, the effect would either be no adaptive
stimulation or too much harmful ROS formation. The sweet spot is somewhere
between, at the top of the bell curve; where you get just enough ROS formation
to excert a beneficial adaptive response, but not enough to cause much harm.
-°Olafur]

That having been stated, there remains the very difficult problem of quantifying
for each activity, food, chemical, radiation type or other environmental
pararmeter, just what is too little or too much, and even more difficult for a
given individual what is the ideal amount - ie. the amounts of all these items
that will together optimize hir health.

With respect to exercise, a simple answer to your question would be that there
is no particular kind of exercise that I view as detrimental per se (as long as
it does not involve something inherently dangerous such as mountain climbing).
As far as studies of exercise, it appears that the numbers of people who
exercise to extremes is so small that no one has yet done a mortality study of
them. I cannot even find any mortality studies for lifelong forced exercise in
animals. Scientists and funding is mainly active in showing the benefits of
exercise and urging more people of all ages to gain those benefits. Therefore, I
will first try to explain why excessive exercise should theoretically be bad for
a person's health and find what studies I can to support this. Hopefully, this
will enable readers to both understand my reasoning and decide reasonable
exercise limits for themselves.

Potential negatives to Excessive Exercise

1. Larger than necessary (for living in a modern hi-tech society) muscle mass
means:
- more tissue that needs to be maintained by the organs (which do not grow in
proportion to the muscle mass),
- more tissue to generate free radicals to invade the rest of the body,
- more tissue to get its DNA damaged and potentially become cancerous,
- more weight on the body's hip, back, and leg joints (which also do not grow
according to the body mass on them, although the bones themselves do strengthen.

These negatives of unneccessary muscle mass are similar to those of excess fat
mass, but fat mass simply has more negatives attached to it.

2. Overstress of muscles and joints generally can cause the following problems:
- Increase in overall oxidative stress
- Altered immune function
- increased local inflammation
- Increased DNA damage
- Osteoporosis
- joint and liagment tears and breaks.

Here are some quotes from abstracts supporting the above:

This first one appears to be about equivalent to running a marathon.

"It has been reported that exercise induces oxidative stress and causes
adaptations in antioxidant defences. The aim of this study was to determine the
adaptations of lymphocytes to the oxidative stress induced by an exhaustive
exercise. Nine voluntary male subjects participated in the study. The exercise
was a cycling mountain stage (171.8 km), and the cyclists took a mean of 283 min
to complete it. Blood samples were taken the morning of the cycling stage day,
after overnight fasting, and 3 h after finishing the stage.....The cycling stage
induced significant increases in blood-oxidized (glutathione/GSSG), plasma MDA
and serum urate levels. The exercise also produced increases in CK and LDH serum
activities.....The protein carbonyl levels increased significantly in
lymphocytes after the stage. In conclusion, in spite of increasing antioxidant
defences in response to the oxidative stress induced by the exhaustive exercise,
lymphocyte oxidative damage was produced after the stage as demonstrated by the
increased carbonyl index even in very well trained athletes." PMID: 16481153

"The main findings of this investigation demonstrate that exhaustive aerobic
exercise induces DNA damage, while antioxidant supplementation does not protect
against damage." Randomized Controlled Trial PMID: 16327031

"Interleukin 18 (IL-18) is an important pro-inflammatory cytokine in the early
phase of human immune response to microbial infections. The influence of
strenuous exercise on the intrinsic balance of IL-18 and its endogenous
antagonist IL-18 binding protein (IL-18 BP) is unknown, but could be of major
relevance for the athlete's immune function empirically and epidemiologically
proven to be altered after exhaustive exertion. To study the effect of strenuous
marathon cycling on the interaction of IL-18 and IL-18 BP we investigated 37
male, healthy, and well-trained amateur cyclists participating in the Otztaler
Radmarathon in Tyrol (distance: 230 km; cumulative altitude difference: 5500
m)....The present study reveals an exercise-induced significant decline in free
IL-18 accompanied by an immediate up-regulation of IL-18 BP and decreased IL-18
in marathon cyclists. This down-regulation of free IL-18 may (i) limit the
magnitude and duration of a too excessive inflammatory response to the
exercise-induced tissue damage and (ii) on the other hand contribute to the
elevated susceptibility to infection in athletes undergoing exhaustive
exercise." PMID: 16320167

[Glutamine, and also branced chain amino acids might help in this regard. Both
have been shown to be helpful in decreasing the susceptibility to infection in
hard training atheletes (PMID: 11985938). -°Olafur]


"It is well established that prolonged, exhaustive endurance exercise is capable
of inducing skeletal muscle damage and temporary impairment of muscle function.
Although skeletal muscle has a remarkable capacity for repair and adaptation,
this may be limited, ultimately resulting in an accumulation of chronic skeletal
muscle pathology. Case studies have alluded to an association between long term,
high volume endurance training and racing, acquired training intolerance, and
chronic skeletal muscle pathology." PMID: 15562162


In the following they do not state the obvious, that exhaustion of division
capacity of satellite cells is not conducive to longevity.

"Although the beneficial health effects of regular moderate exercise are well
established, there is substantial evidence that the heavy training and racing
carried out by endurance athletes can cause skeletal muscle damage. This damage
is repaired by satellite cells that can undergo a finite number of cell
divisions. In this study, we have compared a marker of skeletal muscle
regeneration of athletes with exercise-associated chronic fatigue, a condition
labeled the "fatigued athlete myopathic syndrome" (FAMS), with healthy
asymptomatic age- and mileage-matched control endurance athletes. METHODS:
Muscle biopsies of the vastus lateralis were obtained from 13 patients diagnosed
with FAMS and from 13 healthy control subjects. DNA was extracted from the
muscle samples and their telomeric restriction fragment (TRF) or telomere
lengths were measured by Southern blot analysis. RESULTS: All 13 symptomatic
athletes reported a progressive decline in athletic performance, decreased
ability to tolerate high mileage training, and excessive muscular fatigue during
exercise. The minimum value of TRF lengths (4.0 +/- 1.8 kb) measured on the DNA
from vastus lateralis biopsies from these athletes were significantly shorter
than those from 13 age- and mileage-matched control athletes (5.4 +/- 0.6 kb, P
< 0.05). Three of the FAMS patients had extremely short telomeres (1.0 +/- 0.3
kb). The minimum TRF lengths of the remaining 10 symptomatic athletes (4.9 +/-
0.5 kb, P < 0.05) were also significantly shorter that those of the control
athletes. CONCLUSION: These findings suggest that skeletal muscle from
symptomatic athletes with FAMS show extensive regeneration which most probably
results from more frequent bouts of satellite cell proliferation in response to
recurrent training- and racing-induced muscle injury." PMID: 12972872

"Aerobic exercise enhances endothelium-dependent vasodilation in hypertensive
patients, patients with chronic heart failure, and healthy individuals. However,
it is unclear how the intensity of exercise affects endothelial function in
humans. The purpose of the present study was to determine the effects of
different intensities of exercise on endothelium-dependent vasodilation in
humans.....High-intensity exercise increases plasma concentrations of
8-hydroxy-2'-deoxyguanosine (from 6.7+/-1.1 to 9.2+/-2.3 ng/mL; P<0.05) and
serum concentrations of malondialdehyde-modified low-density lipoprotein (from
69.0+/-19.5 to 82.4+/-21.5 U/L; P<0.05), whereas moderate exercise tended to
decrease both indices of oxidative stress. CONCLUSIONS: These findings suggest
that moderate-intensity aerobic exercise augments endothelium-dependent
vasodilation in humans through the increased production of nitric oxide and that
high-intensity exercise possibly increases oxidative stress." PMID: 12874192

"Excessive stress will induce DNA damage in the form of oxidized nucleosides,
strand breaks, or DNA-protein crosslinks. Possible consequences of DNA damage
are repair, apoptosis/necrosis, or defective repair leading to DNA sequence
alterations and possibly to the development of cancer or, in case of
mitochondrial DNA, to metabolic dysfunction. Excessive exercise will also induce
DNA damage in peripheral leukocytes. The good message is that moderate stress in
form of regular exercise/training may have protective effects against
exercise-induced DNA damage. Up-regulation of endogenous antioxidant defense
systems and complex regulation of repair systems such as heat shock proteins
(HSP 70, HSP 27, HO 1) are seen in response to training and exercise.
Up-regulation of antioxidants and modulation of the repair response may be
mechanisms by which exercise can beneficially influence our health." Review
PMID: 11579749

"Osteoporosis is a systemic skeletal disease characterised by low bone density
and micro architectural deterioration of bone tissue with a consequent increase
in bone fragility and susceptibility to fracture. It is a silent disease. It is
the result of the negative balance between bone formation and bone resorption,
i.e. more bone is lost than is formed. It is the most common bone disease
worldwide and is now a major health problem. Bones require a normal level of
systemic hormones, adequate caloric intake, particularly protein, calcium and
vitamin D and regular weight-bearing exercise throughout life. A large bone mass
early in life protects against osteoporosis. Peak bone mass is determined by
sex, heredity family history, race, diet and exercise. Sixty per cent of bone
growth occurs during adolescence. Moderate exercise protects against
osteoporosis, but too little or excessive exercise may cause osteoporosis."
PMID: 11440416

"In osteoporosis there is a reduction in the protein and mineral matrix of the
bone, with an increase in the risk of fracture, especially of some bones. The
present paper discusses some of the preventive factors relating to nutrition and
life style....Avoiding the following risks, smoking, the abusive consumption of
alcohol, intense weight loss and diets that are extremely hypercaloric, a
sedentary lifestyle and excessive exercise would all be other preventive
measures for osteoporosis." Review PMID: 14716360

"Exertional rhabdomyolysis is a life threatening condition resulting from lysis
of muscle cells after vigorous exercise. It can cause many complications such as
renal failure. It occurs most commonly in military personnel but also in
civilians who have excessive excercise after work." PMID: 12948279


Overtraining is a process of excessive exercise training in high-performance
athletes that may lead to overtraining syndrome.

"Overtraining syndrome (OTS) occurs where an athlete is training vigorously, yet
performance deteriorates. One sign of OTS is suppressed immune function, with an
increased incidence of upper respiratory tract infection (URTI). An increased
incidence of URTIs is also associated with high volume/intensity training, as
well as with excessive exercise (EE), such as a marathon, manifesting between
3-72 hours post-race....This paper hypothesises that exercise-related
immunosuppression is due to tissue trauma sustained during intense exercise,
producing cytokines, which drive the development of a T(H)2 [T-helper type 2]
lymphocyte profile. A T(H)2 cell response results in simultaneous suppression of
CMI [cell-mediated immunity], rendering the athlete susceptible to infection.
Additionally, increased levels of circulating stress hormones (cortisol and
catecholamines), as well as prostaglandin E(2), support up-regulation of T(H)2
lymphocytes. Marathon-related data are presented to support this hypothesis. It
is concluded that an increased incidence of illness associated with OTS and in
response to EE is not due to immunosuppression per se, but rather to an altered
focus of immune function, with an up-regulation of humoral immunity and
suppression of CMI." Review PMID: 12696983

"Overtraining syndrome is a neuroendocrine disorder characterized by poor
performance in competition, inability to maintain training loads, persistent
fatigue, reduced catecholamine excretion, frequent illness, disturbed sleep and
alterations in mood state. Although high-performance athletes are generally not
clinically immune deficient, there is evidence that several immune parameters
are suppressed during prolonged periods of intense exercise training. These
include decreases in neutrophil function, serum and salivary immunoglobulin
concentrations and natural killer cell number and possibly cytotoxic activity in
peripheral blood. Moreover, the incidence of symptoms of upper respiratory tract
infection increases during periods of endurance training. However, all of these
changes appear to result from prolonged periods of intense exercise training,
rather than from the effects of overtraining syndrome itself. At present, there
is no single objective marker to identify overtraining syndrome. It is best
identified by a combination of markers, such as decreases in urinary
norepinephrine output, maximal heart rate and blood lactate levels, impaired
sport performance and work output at 110% of individual anaerobic threshold, and
daily self-analysis by the athlete (e.g. high fatigue and stress ratings). The
mechanisms underlying overtraining syndrome have not been clearly identified,
but are likely to involve autonomic dysfunction and possibly increased cytokine
production resulting from the physical stress of intense daily training with
inadequate recovery." Review PMID: 11050533

"Overtraining is of serious concern to long-distance runners and will affect 65%
of them at some time in their competitive career. The clinical presentation is
nonspecific but the classical symptoms include fatigue, mood disturbances,
frequent upper respiratory infections and injury, and a decrease in performance.
Dysfunction of the hypothalamic pituitary axis from repeated stress, of a
physical or nonphysical nature, represents the most likely pathogenesis of this
condition. There is no single biological marker that is diagnostic of an
overtrained state; however, several parameters deserve further study. The time
to volitional fatigue on a cycle ergometer at an intensity of 110% of the
individual anaerobic threshold represents a possible laboratory test. Salivary
IgA holds promise as a useful immunoligical marker of the overtrained state and
further research is needed to determine the validity of plasma glutamine as a
blood marker. The most promising tool at present is a measure of the athlete's
mood state, and several psychological tools can be used for this purpose."
Review PMID: 9916182


Although the following paper does not conclude that increased free radical
generation from exercise is negative for overall health and longevity, it
nevertheless raises this question and maintains that it needs more study.

"Although assays for the most popular markers of exercise-induced oxidative
stress may experience methodological flaws, there is sufficient credible
evidence to suggest that exercise is accompanied by an increased generation of
free radicals, resulting in a measurable degree of oxidative modifications to
various molecules. However, the mechanisms responsible are unclear. A common
assumption that increased mitochondrial oxygen consumption leads per se to
increased reactive oxygen species (ROS) production is not supported by in vitro
and in vivo data. The specific contributions of other systems (xanthine oxidase,
inflammation, haem protein auto-oxidation) are poorly characterised. It has been
demonstrated that ROS have the capacity to contribute to the development of
muscle fatigue in situ, but there is still a lack of convincing direct evidence
that ROS impair exercise performance in vivo in humans. It remains unclear
whether exercise-induced oxidative modifications have little significance,
induce harmful oxidative damage, or are an integral part of redox regulation. It
is clear that ROS play important roles in numerous physiological processes at
rest; however, the detailed physiological functions of ROS in exercise remain to
be elucidated."
PMID: 16336008


Below is a study which found that the CRP marker of inflammation is decreased by
9 months of training for a marthon. It is too bad that they did not then test
*after* the actual marthon run. Also of course, they did not test these same
subjects as they continued and ran 29 marathons during a year. My view of this
study is that it supports what I have been telling Russell, that if he would do
all the training and *not* run the marathons, that would still be highly
beneficial. It is the *extremity* of running the marathons which I am convinced
is harmful.

"An intense physical exercise induces an inflammatory reaction as demonstrated
by the delayed increase in blood of acute phase proteins and among them of
C-reactive protein (CRP). There is also evidence for a diminished acute phase
reaction due to regular exercise suggesting a suppression of the inflammatory
response through training. With this background CRP was measured by a sensitive
enzyme immunoassay under resting conditions before and after 9 months of
training in 14 subjects preparing for a marathon with the aim of studying the
effect of training on the base-line CRP concentration. The mean distance run per
week increased significantly from 31 +/- 9 km at the beginning to 53 +/- 15 km
after 8 months of training (p < 0.01). The aerobic capacity rose significantly
after training as demonstrated by the increase of running velocity during a
maximal treadmill test from 3.82 +/- 0.29 m/s pre-training to 4.17 +/- 0.17 m/s
post-training at a blood lactate concentration of 4 mmol/L (p < 0.01). In 10 of
12 runners base-line CRP was diminished after training in spite of a continuous
increase of training intensity. The CRP median fell from 1.19 mg/L before to
0.82 mg/L after training (p < 0.05). Since intense physical exercise is known to
be associated with an inflammatory reaction of muscles and tendons, the CRP
decrease was unexpected. In 2 subjects the CRP concentration rose markedly
because of a borrelia infection and a knee injury, respectively. These values
were caused by a pathological condition and were not considered for the
statistical evaluation. In 10 non-training control subjects the CRP median did
not change significantly during the same 9 months period. The decrease of the
CRP base-line concentration after training suggests that intensive regular
exercise has a systemic anti-inflammatory effect. This is of particular interest
with regard to several recent reports confering on the concentration of CRP in
plasma a predictive value for the risk of cardiac infarction, venous thrombosis
or stroke." PMID: 10683094

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

There are also many quotes in abstracts which support moderate, brisk, and
frequent exercise, but nevertheless caution against longer and excessive
sessions of exercise.

"CONCLUSIONS: These data clearly indicate that physical activity is associated
with decreased CHD risk. Furthermore, they lend some support to recent
recommendations that allow for the accumulation of shorter sessions of physical
activity, as opposed to requiring 1 longer, continuous session of exercise. This
may provide some impetus for those sedentary to become more active." PMID:
10961961

"The Harvard Alumni study is reviewed critically with a view to resolving the
apparent conflict between the conclusions drawn from this research and the
current consensus on optimal patterns of physical activity for health. The
optimal energy expenditure reported for the Harvard data set is less than at
first appears, since the estimated expenditures are gross rather than net
values. Further, the optimal energy expenditure has been over-estimated, because
too high a cost was assumed for stair climbing, and sport involvement may also
have been over-reported. The data do not as yet allow the assertion that benefit
is obtained only from vigorous physical activity, and there seems little
conflict with the current consensus on the benefits of moderate physical
activity." PMID: 10090457

"Aging is associated with a linear decline in maximum aerobic capacity. The rate
of decline is twofold greater when comparing sedentary with physically active
middle-aged men. Thus, regular exercise could conceivably lower functional
aerobic age by slowing this functional decline. Exercise, particularly excessive
exercise, is also associated with serious hazards, including sudden death,
nonfatal myocardial infarction, excessive fatigue, hyperthermia, and significant
musculoskeletal problems. Accounts of the health effects of exercise should
consider a wide range of risks and benefits, especially those related to
improving function, minimizing disability, and prolonging independent living."
Review PMID: 3545119

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

Here is a study about the "excessive behavior" aspect of exercise.

"There is accumulating evidence that young men have become as concerned with
their physical appearance as young women. However, different from women who want
to achieve an ultra-slender body shape, most men want to increase their muscle
mass and body size. Women with anorexia nervosa (AN) and competitive male
bodybuilders are those who have taken the cultural standards of bodily
perfection to the extreme, and both use unhealthy behaviours such as severe food
restriction, excessive exercise, and steroids in pursuit of their goals.
Findings of this study confirmed our prediction that the psychological profile
of bodybuilders would be very similar to that found in women with AN. Both
groups were significantly more obsessional, perfectionistic, anhedonic, and
pathologically narcissistic than the general population. However, the
bodybuilders reported very positive perceptions of their self-worth while the AN
patients had very negative perceptions. Results are interpreted in the framework
of a speculative developmental model of AN and bodybuilding, which focuses on
the role of personality in the initiation and maintenance of excessive
behaviours." PMID: 15001065

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

Here is a paper which makes a case for the value of many different kinds of
exercise, but note that none of these are more than brisk and moderate.

"Lack of exercise is a primary cause for today's level of morbidity and
mortality in the Western world. Thus, exercise as a therapeutic modality has an
important role. Beneficial effects of exercise have been extensively documented,
specifically in primary and secondary prevention of coronary heart disease
(CHD), diabetes mellitus, hypertension, disorders of fat metabolism, heart
insufficiency, cancer, etc. A regular (at least 3 x per week) endurance training
program of 30-40 min duration at an intensity of 65-70% of VO(2)max involving
large muscle groups is recommended. The specific exercise activity can also
positively affect individuals with orthopedic disease patterns, i.e.,
osteoporosis, back pain, postoperative rehabilitation, etc. Endurance strength
training in the form of sequential training involving approx. 8-10 different
exercises for the most important muscle groups 2 x per week is a suitable
exercise therapy. One to three sets with 8-12 repetitions per exercise should be
performed until volitional exhaustion of the trained muscle groups among healthy
adults and 15-20 repetitions among older and cardiac patients. Apart from a
positive effect on the locomotor system, this type of strength training has
positive effects on CHD, diabetes mellitus, and cancer." PMID: 16086193

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

Since humans have the ability to make themselves do things which no animal would
voluntarily do (what animal would continue to exercise after it starts to hurt
unless it is starving and the exercise is necessary to gain food?), I think that
excessive human exercise can reasonably be compared with *forced* animal
exercise. Therefore, I have also looked at studies in that area. Here the
results begin to become clearer.

"Regular physical exercise has emerged, together with dietary restriction, as an
effective intervention in delaying degenerative diseases and augmenting life
span in rodents. The mechanisms involved remain largely unknown, although a
beneficial influence on the age-related alteration of insulin sensitivity has
been hypothesized. As muscle triglyceride (TG) accumulation is considered a
reliable index of muscle insulin resistance, in this study we explored muscle TG
content in 23-month-old male Sprague-Dawley rats subjected to life-long
training. Plasma glucose, insulin, free fatty acid (FFA) and leptin levels were
also measured. Both voluntary running in wheels (RW) and forced training in
treadmill (TM) were studied. As RW rats weighed less than controls, a cohort of
untrained animals, fed to pair weight (PW) with RW, was added to discriminate
the effect of exercise from that of food restriction. Sedentary ad libitum fed
rats served as controls. In 23-month-old RW rats, muscle TG content was reduced
by 50% with respect to age-matched sedentary controls, while in TM group this
reduction was smaller but still highly significant, and occurred independently
on the changes in body fat mass. In both the trained rat groups, there was a
significant decrease in circulating FFA levels and a trend to reduced insulin
levels. In PW rats, muscle TG levels decreased similarly to RW rats, while
plasma parameters were less modified. In particular, RW training was more
effective than PW in preventing the age-related increase in circulating leptin
levels. Our results suggest that voluntary exercise effectively counteracts the
development of insulin resistance in the muscles of ageing rats as well as other
related changes such as hyperlipacidaemia and compensatory hyperleptinaemia.
Forced training or moderate food restriction appear slightly less effective than
voluntary exercise in preventing age-dependent alterations in nutrient
distribution and/or utilization." PMID: 15489056

"The importance of maintaining physical fitness by engaging in exercise in a
life-long perspective as well as the avoidance of obesity has been emphasised in
recent years by epidemiological studies on human populations as well as studies
on laboratory rodents. In laboratory studies, voluntary running in wheels and
forced training in a treadmill have been used with beneficial results.
Restriction of the food intake of sedentary laboratory rodents can be regarded
either as life prolongation or prevention of life shortening by obesity. We
compared the effects of these interventions on male Sprague-Dawley rats from the
age of 5 to 23 months in the following groups: (1) RW=voluntary running in
wheels; (2) PW=fed to pair weight with RW animals; (3) TM=forced training in a
treadmill; and (4) S1=sedentary with ad libitum access to food. Each group
consisted of 32 animals, all housed individually in cages. Two RW animals died,
five died in each of the PW and S1 groups and 10 in the TM group (p<0.05). The
S1 and TM groups gained most weight, the TM less after the age of 21 months
(p<0.05). The body weights of the RW group was lower than those of the S1 and TM
groups all the time (p<0.001) and the difference increased all the time. Body
composition was analysed by bioelectrical impedance analysis. There were no
differences in fat free mass (FFM) neither between RW and PW at any time, nor
between S1 and TM. FFM was lower for RW and PW compared to S1 and TM. TM gained
FFM until the age of 17 months, while S1 gained FFM all the time. S1 gained fat
all the time, but the gain for TM levelled off. It stayed constant for RW until
13 months and decreased afterwards. We conclude that voluntary running in wheels
enhances survival and keeps body fat lower than in PW animals up to the age of
17 months. Body composition and survival data suggest that voluntary running is
more optimal than forced. Care must, however, be taken in analyses, since RW is
a heterogenous group because there is a large variation between the animals with
respect to how much they run." PMID: 11672990


Based on the theory that animal lifespan is inversely proptional to metabolic
rate (this is true across all species even though there are major variations
between closely related species - for example bats live far longer than mice but
differ little in metabolic rate), the following paper would imply that heavy
exercise is negative for longevity (basically one wears oneself out faster).

"1. The energy metabolism of ad lib.-fed adult male Wistar rats receiving daily
running exercise (0.9 km/d; 8 degrees incline) on a motor-driven treadmill, over
a period of 56 d, was compared with that of sedentary ad lib.-fed rats and
sedentary restricted-fed rats of similar body-weight (approximately 420 g).
................
3. Exercise-trained rats ate 5% more food than the sedentary ad lib.-fed rats
but their equilibrium body-weight was 60 g lower than that of the latter group.
4. Resting metabolic rate, measured over 22 h in a respiration chamber was
increased by 10% in exercise-trained animals.
5. Feeding increased energy expenditure (dietary-induced thermogenesis) and this
effect was potentiated by performance of an exercise task.
6. Exercise-trained rats exhibited anticipatory rises in energy expenditure
(approximately 40%) when placed on a stationary treadmill.
7. Treadmill work increased energy expenditure by a factor of 1.9-2.4.
8. The energy cost of the exercise, determined by respiration calorimetry was
66-80 J/g per km. These energy costs did not account for all the differences
observed in food energy consumption of exercise-trained and sedentary rats of
equal body-weight.
9. It is concluded that regular physical exercise increases energy expenditure
by factors additional to the energy requirement directly related to the physical
work. These factors include an increased resting metabolic rate in
exercise-trained rats, increased dietary thermogenesis induced by exercise and
anticipatory increases in energy metabolism during the period preceding
exercise." PMID: 7066285


Hollozy has done many interesting and important studies in animals on CR and
exercise of which the following is one which also corrects an earlier one. The
main conclusion is that exercise does not provide any *additional* longevity
benefit to food restriction (which in his studies is quite severe).

"Food restriction increases the maximal longevity of rats. Male rats do not
increase their food intake to compensate for the increase in energy expenditure
in response to exercise. However, a decrease in the availability of energy for
growth and cell proliferation that induces an increase in maximal longevity in
sedentary rats only results in an improvement in average survival, with no
extension of maximal life span, when caused by exercise. In a previous study
(J.O. Holloszy and K.B. Schechtman. J. Appl. Physiol. 70:1529-1535, 1991), to
test the possibility that exercise prevents the extension of life span by food
restriction, wheel running and food restriction were combined. The
food-restricted runners showed the same increase in maximal life span as
food-restricted sedentary rats but had an increased mortality rate during the
first one-half of their mortality curve. The purpose of the present study was to
determine the pathological cause of this increased early mortality. However, in
contrast to our previous results, the food-restricted wheel-running rats in this
study showed no increase in early mortality, and their survival curves were
virtually identical to those of sedentary animals that were food restricted so
as to keep their body weights the same as those of the runners. Thus it is
possible that the rats in the previous study had a health problem that had no
effect on longevity except when both food restriction and exercise were
superimposed on it. Possibly of interest in this regard, the rats in this study
did considerably more voluntary running than those in the previous study. It is
concluded that 1) moderate caloric restriction combined with exercise does not
normally increase the early mortality rate in male rats, 2) exercise does not
interfere with the extension of maximal life span by food restriction, and 3)
the beneficial effects of food restriction and exercise on survival are not
additive or synergistic." PMID: 9049716

--Paul]

[In addition to all the items Paul provided above, I came across an editorial in
a 2003 issue of Physiological Genomics regarding a paper in that same issue -
the purpose of which was to "assess the changes in gene expression that occur in
the hearts of both sedentary and active mice and to determine what effect
exercise had upon genes demonstrated to be differentially regulated in the
sedentary animals." (PMID: 12429864) The mice used were a selected due to their
high volume of voluntary running. The editors raised several questions about the
study; among them:
"Would access to treadmills have a similar effect in ordinary mice? Would forced
exercise have the same effect as voluntary exercise, or would it have the
opposite effect? How much exercise is needed to retard aging at the level of
gene expression?"
http://biology.ucr.edu/people/faculty/Garland/Welle&Glueck2003.pdf

These are questions that deserve answers and I hope that further studies will
produce some substantial ones. **Kitty]