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1.
Physiol Rev ; 97(2): 699-720, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28202600

RESUMO

It has been suggested that highly social mammals, such as naked mole rats and humans, are long-lived due to neoteny (the prolongation of youth). In both species, aging cannot operate as a mechanism facilitating natural selection because the pressure of this selection is strongly reduced due to 1) a specific social structure where only the "queen" and her "husband(s)" are involved in reproduction (naked mole rats) or 2) substituting fast technological progress for slow biological evolution (humans). Lists of numerous traits of youth that do not disappear with age in naked mole rats and humans are presented and discussed. A high resistance of naked mole rats to cancer, diabetes, cardiovascular and brain diseases, and many infections explains why their mortality rate is very low and almost age-independent and why their lifespan is more than 30 years, versus 3 years in mice. In young humans, curves of mortality versus age start at extremely low values. However, in the elderly, human mortality strongly increases. High mortality rates in other primates are observed at much younger ages than in humans. The inhibition of the aging process in humans by specific drugs seems to be a promising approach to prolong our healthspan. This might be a way to retard aging, which is already partially accomplished via the natural physiological phenomenon neoteny.


Assuntos
Envelhecimento/fisiologia , Hominidae/metabolismo , Longevidade/fisiologia , Neoplasias/metabolismo , Estresse Oxidativo/fisiologia , Animais , Evolução Biológica , Humanos
2.
FEBS Lett ; 587(13): 2018-24, 2013 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-23665033

RESUMO

Since the times of the Bible, an extract of black cumin seeds was used as a medicine to treat many human pathologies. Thymoquinone (2-demethylplastoquinone derivative) was identified as an active antioxidant component of this extract. Recently, it was shown that conjugates of plastoquinone and penetrating cations are potent mitochondria-targeted antioxidants effective in treating a large number of age-related pathologies. This review summarizes new data on the antioxidant and some other properties of membrane-penetrating cationic compounds where 2-demethylplastoquinone substitutes for plastoquinone. It was found that such a substitution significantly increases a window between anti- and prooxidant concentrations of the conjugates. Like the original plastoquinone derivatives, the novel compounds are easily reduced by the respiratory chain, penetrate through model and natural membranes, specifically accumulate in mitochondria in an electrophoretic fashion, and strongly inhibit H2O2-induced apoptosis at pico- and nanomolar concentrations in cell cultures. At present, cationic demethylplastoquinone derivatives appear to be the most promising mitochondria-targeted drugs of the quinone series.


Assuntos
Antioxidantes/farmacologia , Mitocôndrias/efeitos dos fármacos , Plastoquinona/análogos & derivados , Plastoquinona/farmacologia , Animais , Antioxidantes/metabolismo , Benzoquinonas/metabolismo , Benzoquinonas/farmacologia , Cátions , Permeabilidade da Membrana Celular , Sistemas de Liberação de Medicamentos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Oxirredução , Plastoquinona/metabolismo , Espécies Reativas de Oxigênio/metabolismo
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