2007, Piran, Slovenia

Environmental Ergonomics XII
Igor B. Mekjavic, Stelios N. Kounalakis & Nigel A.S. Taylor (Eds.), © BIOMED, Ljubljana 2007
Invited presentation
ALTITUDE PHYSIOLOGY:
FROM THE INTEGRATIVE TO THE MOLECULAR LEVEL
Paolo Cerretelli
Department of Sciences and Biomedical Technologies, University of Milano, Milano,
Italy.
Contact person: paolo.cerretelli@unimi.it
INTRODUCTION
Human aerobic performance at high altitude is known to be affected by functional
adaptations mainly of hematologic, respiratory and cardiovascular nature that are, in
part, population-specific. As a consequence of prolonged (2-3 months) altitude
exposure, maximum aerobic power ( V .
O2max) undergoes a reduction that, on average,
at 3500 m is 35% of the sea level control value, reaching 85 to 90% on the top of Mt.
Everest (8850 m).
The altitude-induced decrease of V .
O2max is characterized by a large variability due
to several factors, e.g., ethnic background, individual fitness and training conditions,
etc. In this context, it has been shown that, both among Caucasians and Tibetans, the
relative decrease of V .
O2max is greater in subjects characterized by higher control
levels of maximum aerobic power (Marconi et al., 2004). On the other hand, second
generation Tibetans born at moderate altitude, after one month exposure to 5000 m
undergo a lesser drop of V .
O2max (-10%) than acclimatized Caucasians (-40%). The
above described different reactions to hypoxia among subjects, particularly those
based on ethnical grounds, are likely the consequence of varying adaptational
characteristics of some of the factors regulating convective and diffusive transport of
oxygen from the environment to the tissues the mechanisms of which, however, need
further investigation. Over the last decade, besides the hematologic and cardiorespiratory
systems, muscle has been indicated as a possible site of impairment of
exercise performance. Indeed, in caucasian mountaineers, after 10 to 12 weeks
exposure to 5000 meters and above, muscle has been found to deteriorate (-25% of
mass; -25% of mitochondrial volume density and oxidative enzyme activity; 3-fold
increase in the accumulation of lipofuscin, an undegradable waste material and a
marker of damage by reactive oxygen species, ROS). By contrast and rather
surprisingly, native Tibetans (Sherpa) living at around 4000 m are characterized by
reduced (-25%) muscle mitochondrial volume density compared to caucasian
lowlanders but by normal lipofuscin and protein carbonyl derivatives accumulation,
with no signs of ROS damage and, moreover, by improved exercise economy, i.e.
lower oxygen consumption for given submaximal work loads (Marconi et al., 2005).
Therefore, the hypothesis was put forward that altitude natives be characterized by a
more efficient ROS scavenging system allowing them to live and thrive in chronic
hypoxia.
METHODS
In order to identify hypothetical molecular markers of muscle deterioration in chronic
hypoxia and of possible compensatory mechanisms, 2 DE and/or 2D-DIGE human
78