Decrease In Bioenergetics Research Articles

Role of estrogen in the regulation of central and peripheral energy homeostasis: from a menopausal perspective.

Estrogen plays a prominent role in regulating and coordinating energy homeostasis throughout the growth, development, reproduction, and aging of women. Estrogen receptors (ERs) are widely expressed in the brain and nearly all tissues of the body. Within the brain, central estrogen via ER regulates appetite and energy expenditure and maintains cell glucose metabolism, including glucose transport, aerobic glycolysis, and mitochondrial function. In the whole body, estrogen has shown beneficial effects on weight control, fat distribution, glucose and insulin resistance, and adipokine secretion. As demonstrated by multiple in vitro and in vivo studies, menopause-related decline of circulating estrogen may induce the disturbance of metabolic signals and a significant decrease in bioenergetics, which could trigger an increased incidence of late-onset Alzheimer's disease, type 2 diabetes mellitus, hypertension, and cardiovascular diseases in postmenopausal women. In this article, we have systematically reviewed the role of estrogen and ERs in body composition and lipid/glucose profile variation occurring with menopause, which may provide a better insight into the efficacy of hormone therapy in maintaining energy metabolic homeostasis and hold a clue for development of novel therapeutic approaches for target tissue diseases.

The Mechanism of Programmed Aging: The Way to Create a Real Remedy for Senescence.

BackgroundAccumulation of various damages is considered the primary cause of aging throughout the history of gerontology. No progress has been made in extending animal lifespan under the guidance of this concept. This concept denies the existence of longevity genes, but it has been experimentally shown that manipulating genes that affect cell division rates can increase the maximum lifespan of animals. These methods of prolonging life are unsuitable for humans because of dangerous side effects, but they undoubtedly indicate the programmed nature of aging.ObjectiveThe objective was to understand the mechanism of programmed aging to determine how to solve the problem of longevity.MethodsFundamental research has already explored key details relating to the mechanism of programmed aging, but they are scattered across different fields of knowledge. The way was to recognize and combine them into a uniform mechanism.ResultsOnly a decrease in bioenergetics is under direct genetic control. This causes many different harmful processes that serve as the execution mechanism of the aging program. The aging rate and, therefore, lifespan are determined by the rate of cell proliferation and the magnitude of the decrease in bioenergetics per cell division in critical tissues.ConclusionThe mechanism of programmed aging points the way to achieving an unlimited healthy life; it is necessary to develop a means for managing bioenergetics. It has already been substantially studied by molecular biologists and is now waiting for researchers from gerontology.

31P and1H MRS of DB‐1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan

In vivo (31) P MRS demonstrates that human melanoma xenografts in immunosuppressed mice treated with lonidamine (LND, 100 mg/kg intraperitoneally) exhibit a decrease in intracellular pH (pH(i) ) from 6.90 ± 0.05 to 6.33 ± 0.10 (p < 0.001), a slight decrease in extracellular pH (pH(e) ) from 7.00 ± 0.04 to 6.80 ± 0.07 (p > 0.05) and a monotonic decline in bioenergetics (nucleoside triphosphate/inorganic phosphate) of 66.8 ± 5.7% (p < 0.001) relative to the baseline level. Both bioenergetics and pH(i) decreases were sustained for at least 3 h following LND treatment. Liver exhibited a transient intracellular acidification by 0.2 ± 0.1 pH units (p > 0.05) at 20 min post-LND, with no significant change in pH(e) and a small transient decrease in bioenergetics (32.9 ± 10.6%, p > 0.05) at 40 min post-LND. No changes in pH(i) or adenosine triphosphate/inorganic phosphate were detected in the brain (pH(i) , bioenergetics; p > 0.1) or skeletal muscle (pH(i) , pH(e) , bioenergetics; p > 0.1) for at least 120 min post-LND. Steady-state tumor lactate monitored by (1) H MRS with a selective multiquantum pulse sequence with Hadamard localization increased approximately three-fold (p = 0.009). Treatment with LND increased the systemic melanoma response to melphalan (LPAM; 7.5 mg/kg intravenously), producing a growth delay of 19.9 ± 2.0 days (tumor doubling time, 6.15 ± 0.31 days; log(10) cell kill, 0.975 ± 0.110; cell kill, 89.4 ± 2.2%) compared with LND alone of 1.1 ± 0.1 days and LPAM alone of 4.0 ± 0.0 days. The study demonstrates that the effects of LND on tumor pH(i) and bioenergetics may sensitize melanoma to pH-dependent therapeutics, such as chemotherapy with alkylating agents or hyperthermia.