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Mechanisms and Biomarkers (WG 4) page 22
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diseases occurring with high prevalence and designated degenerative diseases including
cardiovascular diseases and cancers but also osteoporosis, cataracts and neurodegeneration.
Because of the expected increase of aged people in western countries, many investigations
attempt to increase the half-life as well as the maximum life span which may have important
implications in terms of the social and economic points of view for our societies. In humans,
the role of oxidative stress in ageing was suggested by the increase, with age of oxidised
DNA bases, oxidised lipids and oxidised proteins (Meccoci et al., 1999). The role of oxidative
stress in ageing was better assessed by increasing superoxide and catalase expression in
drosophila (Orr and Sohal, 1994). These transgenic flies had live 13% longer than controls. In
humans, the role of oxidative stress in the pathogenicity of degenerative diseases is
recognised but it is not known whether reactive oxygen species are primary or secondary
effectors (Markesbery, 1997). Many studies focused on mitochondria which are the greatest
source of reactive oxygen species and which also show age-associated oxidative damage (in
lipids, proteins and DNA) and DNA mutations (Wei, 1998) and thus may be at the origin of
neuro degenerative diseases. However, recent observation by Urano et al. (1998) on
mitochondrial function in Parkinson’s disease concluded that similar changes were observed
in control that can be attenuated by vitamin E. Another important area of research on ageing
is the effect of caloric restriction known to retard ageing. Recent studies also demonstrated
that caloric restriction also considerably attenuates the oxidative stress evidenced by a
decrease of oxidised tyrosine, amelioration of age-associated increase of cytokines;
prevention of mitochondrial deletions in the liver or reduction of protein and lipid oxidative
damage (Byung, 1996). From these latter observations questions arise as to whether
supplemental antioxidants slow the ageing process. The high complexity of the ageing
process led the gerontologists to consider that it is part of the pathological process. The data
obtained on antioxidant supplementation trials already show a positive relation with agerelated
chronic diseases such as cancer, heart diseases or diabetes. These data provide
evidence that antioxidants may attenuate the pathological process. Other studies on different
species (fruit flies, nematodes, and rats) also showed that antioxidants significantly extend of
median life spans and some of maximum life span. Unfortunately, in these latter studies, no
physiological parameters were measured. One study on mouse supplementation with
mercaptoethanol (Heidrick et al., 1984) demonstrates that median and maximum life spans are
increased by 15% together with improved immune function, a functional age-related
biomarker. Interestingly, vitamin E is now recognised to act as an immune stimulant
(Meydani et al., 1995).