Estrogens promote mitochondrial biogenesis, efficiency,
and protection against oxidative stress [25]. Mitochondria of females accumulate less calcium [65] and have a lower
probability of PTP opening, thus protecting female cells against mitochondria-triggered cell death. These effects could
be partially mediated by estrogens.
This argues in favor of a lower susceptibility to cell death of female cells.
Ageing is characterized by decreased production of sexual steroid hormones especially in women after menopause. Decreasing levels of hormones promote tissue degeneration and age-related pathologies. Decline in sex steroid hormones and accumulation of mitochondrial damage may create a positive feedback loop that contributes to the progressive degeneration in tissue function during ageing [25].
In old but not senescent male and female monkeys, cardiac ageing is characterized by decreased expression of glycolytic enzymes and reduced capacity for oxygen consumption in males but not females [78].
Conversely females produce less mitochondrial free radicals and have a higher content of antioxidant enzymes
than males [50,60,61,82]. The effectiveness of estrogens against age-related diseases may arise in part from hormonal
effects on mitochondrial function.
ERs and their signaling cascade have been implicated [60] in the control of antioxidant enzyme expression.It thus appears that estrogens, mitochondrial capacity, and reactive oxygen species are good candidates to explain the mechanism mediating delayed ageing and cardiovascular risk in females.
Available data suggest that the pathophysiology of the metabolic syndrome and its contribution to the relative risk
of cardiovascular events and HF show gender differences [106]. Glucose tolerance progressively declines with age,
and there is a high prevalence of T2D in elderly people with increased incidence in men. In rodent models, T2D
occurs more frequently or even exclusively in males [107,10
Oxidative stress specially affects the brain mitochondrial function. Brain mitochondria from female rats have less
oxidative damage than males whatever the age [58]. In mouse brain, lower oxidative stress was found in mitochon-
dria of young females compared with males, independently of estrus cycle [40]. However, the brain mitochondria
from young male mice have a better glutathione cycle than female mice, a difference that disappears at 10 months of
age [41].
Mitochondria from female rat liver produce half the amount of peroxides than those of males and have a higher
content of antioxidant enzymes [59,60]. This is due to higher expression and activities of Mn-SOD and of glutathione
peroxidase in females, leading to lower oxidative damage to key mitochondrial components in females than in males
[60]
At physiological concentrations, estrogens protect heart mitochondria from high calcium-induced release of cytochrome c [66].
Thus mitochondria from females seem to better tolerate calcium overload, which may contribute to the better
tolerance to ischemia/reperfusion injury.
ROS have emerged as the main proximate cause of ageing. Mitochondria have been involved as key players first
because they are an important source of free radicals, especially in highly oxidative tissues, and second because they
are a direct target of oxidative damage in ageing cells.
Targetting catalase (a detoxifying enzyme) to mitochondria increases murine life span and protects against age-related diseases [80]. These intriguing results support the idea that mitochondrial ROS may be an important limiting factor in mammalian longevity [80]. A study on skeletal muscle oxidative stress during ageing showed that men may be potentially more vulnerable to oxidative damage than women
[81]. Conversely females produce less mitochondrial free radicals and have a higher content of antioxidant enzymes
than males [50,60,61,82].
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