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1.
EMBO Rep ; 24(12): e56984, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37955230

RESUMO

Aging is accompanied by a decreased DNA repair capacity, which might contribute to age-associated functional decline in multiple tissues. Disruption in hormone signaling, associated with reproductive organ dysfunction, is an early event of age-related tissue degeneration, but whether it impacts DNA repair in nonreproductive organs remains elusive. Using skin fibroblasts derived from healthy donors with a broad age range, we show here that the downregulation of expression of XRCC4, a factor involved in nonhomologous end-joining (NHEJ) repair, which is the dominant pathway to repair somatic double-strand breaks, is mediated through transcriptional mechanisms. We show that the androgen receptor (AR), whose expression is also reduced during aging, directly binds to and enhances the activity of the XRCC4 promoter, facilitating XRCC4 transcription and thus stabilizing the genome. We also demonstrate that dihydrotestosterone (DHT), a powerful AR agonist, restores XRCC4 expression and stabilizes the genome in different models of cellular aging. Moreover, DHT treatment reverses senescence-associated phenotypes, opening a potential avenue to aging interventions in the future.


Assuntos
Androgênios , Reparo do DNA por Junção de Extremidades , Androgênios/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA/genética , Transdução de Sinais , Humanos
2.
Micromachines (Basel) ; 14(6)2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37374810

RESUMO

Porous metal foam with complex opening geometry has been used as a flow field to enhance the distribution of reactant gas and the removal of water in polymer electrolyte membrane fuel cells. In this study, the water management capacity of a metal foam flow field is experimentally investigated by polarization curve tests and electrochemical impedance spectroscopy measurements. Additionally, the dynamic behavior of water at the cathode and anode under various flooding situations is examined. It is found that obvious flooding phenomena are observed after water addition both into the anode and cathode, which are alleviated during a constant-potential test at 0.6 V. Greater abilities of anti-flooding and mass transfer and higher current densities are found as the same amount of water is added at the anode. No diffusion loop is depicted in the impedance plots although a 58.3% flow volume is occupied by water. The maximum current density of 1.0 A cm-2 and the lowest Rct around 17 mΩ cm2 are obtained at the optimum state after 40 and 50 min of operation as 2.0 and 2.5 g of water are added, respectively. The porous metal pores store a certain amount of water to humidify the membrane and achieve an internal "self-humidification" function.

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