Ion Channels

Publication Title: 
Experimental Gerontology

Uncoupling proteins (UCPs) can dissipate mitochondrial protonmotive force by increasing the proton conductance of the inner membrane and through this effect could decrease ROS production, ameliorate oxidative stress and extend lifespan. We investigated whether ubiquitous, pan-neuronal or neurosecretory cell-specific expression of human UCP3 (hUCP3) in adult Drosophila melanogaster affected lifespan.

Author(s): 
Humphrey, Dickon M.
Toivonen, Janne M.
Giannakou, Maria
Partridge, Linda
Brand, Martin D.
Publication Title: 
Experimental Gerontology

The brown fat specific UnCoupling Protein 1 (UCP1) is involved in thermogenesis, a process by which energy is dissipated as heat in response to cold stress and excess of caloric intake. Thermogenesis has potential implications for body mass control and cellular fat metabolism. In fact, in humans, the variability of the UCP1 gene is associated with obesity, fat gain and metabolism. Since regulation of metabolism is one of the key-pathways in lifespan extension, we tested the possible effects of UCP1 variability on survival.

Author(s): 
Rose, Giuseppina
Crocco, Paolina
D'Aquila, Patrizia
Montesanto, Alberto
Bellizzi, Dina
Passarino, Giuseppe
Publication Title: 
Nature

The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis.

Author(s): 
Kim, Eun Bae
Fang, Xiaodong
Fushan, Alexey A.
Huang, Zhiyong
Lobanov, Alexei V.
Han, Lijuan
Marino, Stefano M.
Sun, Xiaoqing
Turanov, Anton A.
Yang, Pengcheng
Yim, Sun Hee
Zhao, Xiang
Kasaikina, Marina V.
Stoletzki, Nina
Peng, Chunfang
Polak, Paz
Xiong, Zhiqiang
Kiezun, Adam
Zhu, Yabing
Chen, Yuanxin
Kryukov, Gregory V.
Zhang, Qiang
Peshkin, Leonid
Yang, Lan
Bronson, Roderick T.
Buffenstein, Rochelle
Wang, Bo
Han, Changlei
Li, Qiye
Chen, Li
Zhao, Wei
Sunyaev, Shamil R.
Park, Thomas J.
Zhang, Guojie
Wang, Jun
Gladyshev, Vadim N.
Publication Title: 
The International Journal of Biochemistry & Cell Biology

Calorie-restricted feeding retards the rate of ageing in mammalian and invertebrate species. The molecular mechanisms underlying this effect include a lower rate of accrual of tissue oxidative damage that is associated with a significantly lower rate of mitochondrial free radical generation in rodent species. To identify the important sites of control and regulation for mitochondrial free radical generation during ageing and calorie-restricted feeding, metabolic control analysis is being applied to the study of mitochondrial bioenergetics.

Author(s): 
Merry, B. J.
Publication Title: 
Aging Cell

Loss of nonshivering thermogenesis in mice by inactivation of the mitochondrial uncoupling protein gene (Ucp1-/- mice) causes increased sensitivity to cold and unexpected resistance to diet-induced obesity at a young age. To clarify the role of UCP1 in body weight regulation throughout life and influence of UCP1 deficiency on longevity, we longitudinally analyzed the phenotypes of Ucp1-/- mice maintained in a room at 23 degrees C.

Author(s): 
Kontani, Y.
Wang, Y.
Kimura, K.
Inokuma, K.-I.
Saito, M.
Suzuki-Miura, T.
Wang, Z.
Sato, Y.
Mori, N.
Yamashita, H.
Publication Title: 
Cell Metabolism

Age-related disease, not aging per se, causes most morbidity in older humans. Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression diminishes age-related disease in three mouse models. In a longevity study, median survival was increased in UCP mice (animals with skeletal muscle-specific UCP1 expression), and lymphoma was detected less frequently in UCP female mice. In apoE null mice, a vascular disease model, diet-induced atherosclerosis was decreased in UCP animals.

Author(s): 
Gates, Allison C.
Bernal-Mizrachi, Carlos
Chinault, Sharon L.
Feng, Chu
Schneider, Jochen G.
Coleman, Trey
Malone, James P.
Townsend, R. Reid
Chakravarthy, Manu V.
Semenkovich, Clay F.
Publication Title: 
Current Aging Science

The discovery of novel uncoupling proteins (UCP2 and UCP3) over 10 years ago heralded a new era of research in mitochondrial uncoupling in a diverse range of tissues. Despite the research vigor, debate stills surrounds the exact function of these uncoupling proteins. For example, the level of uncoupling, the mechanism and mode of action are all under-appreciated at this point in time. Our recent work has used genetic mouse models to focus on the physiological relevance of UCP2. We have used these mouse models to better appreciate the role UCP2 in human health and disease.

Author(s): 
Andrews, Zane B.
Publication Title: 
Neurobiology of Aging

Silent information regulator 1 (SIRT1) is a type of histone deacetylase whose activity is dependent on nicotinamide adenine dinucleotide. SIRT1 plays a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of SIRT1 was reported for neurological diseases. The focus of this review is to summarize the protective effects of SIRT1 in cerebral ischemia. First, the posttranslational modifications of SIRT1 are illustrated; then, we discuss the roles of SIRT1 in cerebral immune homeostasis.

Author(s): 
Yang, Yang
Duan, Weixun
Li, Yue
Yan, Juanjuan
Yi, Wei
Liang, Zhenxing
Wang, Ning
Yi, Dinghua
Jin, Zhenxiao
Publication Title: 
Current Topics in Medicinal Chemistry

Patch-Clamp electrophysiology, the "gold standard" for the functional study of ion channels has become automated. This innovative technology, already over a decade old, has revolutionized the strategies for the search of medicinal compounds which now can be screened at unprecedented speed, approaching the high throughput standards required by primary screening campaigns emblematic of the pharmaceutical and biotechnology industries. Consequently, an acceleration of the discovery and development of new drugs targeting ion channels is expected.

Author(s): 
Picones, Arturo
Publication Title: 
Methods and Findings in Experimental and Clinical Pharmacology

The present study explores pharmacologically on the model spontaneously beating 3H-noradrenaline pretreated guinea-pig atrial preparation the mechanism(s) by which the representative central nervous system (CNS) stimulant drug 3-methyl-3-ethylglutarimide (bemegride, MEG) and its representative CNS depressant homologue 3-methyl-3-n-butylglutarimide (MBG) affect transmitter release and the force and rate of atrial contraction and contracture, as well as the relevance of these atrial mechanism(s) to those involved in the production of drug-evoked convulsions and hypnosis in the mammalian CNS.

Author(s): 
Arblaster, C. I.
Cameron, D. W.
Lavi, Y.
Laycock, G. M.
Shulman, A.

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