Mitochondrial and Energy Production

A surprising number of mutations or partial gene disruptions that extend the longevity of simple organisms, especially nematodes, compromise or reduce mitochondrial function (166,167). In mammals, however, compromised mitochondrial function generally shortens life span (168,169). Moreover, in both in vivo and cell culture studies, it also increases the susceptibility to cellular senescence and apoptosis (170,171).

However, recent findings suggest that subtle perturbations to mitochondrial function and energy production can modestly extend life span in mouse models. For example, within a cohort of outbred mice, animals with relatively higher mitochondrial uncoupling produce lower levels of reactive oxygen species and are relatively longer lived (172). Likewise, a partial reduction in CKL-1, a mitochondrial protein that is important for the synthesis of the mobile electron carrier ubiquinone, modestly increases the life span of both nematodes and mice (173). Recently, a transgenic mouse model with reduced core body temperature was created by overexpressing a mitochon-drial uncoupling protein in neurons that control body temperature (174). These animals presumably expended less energy, and showed a modest increase in life span (12-20%). These and other studies support the idea that mitochondrially generated oxidative stress is an important cause of aging, and that manipulations that reduce this stress promote longevity. Nonetheless, the life span extensions achieved by reducing mitochondrial oxidation reactions or energy production are small, almost certainly because mitochondria are also crucial for life in complex organisms and therefore can tolerate only minor manipulations before vital functions are compromised.

How to Stay Young

How to Stay Young

For centuries, ever since the legendary Ponce de Leon went searching for the elusive Fountain of Youth, people have been looking for ways to slow down the aging process. Medical science has made great strides in keeping people alive longer by preventing and curing disease, and helping people to live healthier lives. Average life expectancy keeps increasing, and most of us can look forward to the chance to live much longer lives than our ancestors.

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