Acarbose improves health and lifespan in aging HET3 mice

To follow‐up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log‐rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%–11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2‐(2‐hydroxyphenyl) benzothiazole (HBX), and INT‐767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose‐control drugs in humans.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148418/1/acel12898.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148418/2/acel12898_am.pd

Ekstrakcija lipofilnih antioksidansa iz nativnih genotipova rajčice pomoću zelenih tehnologija

Research background. Tomato (Solanum lycopersicum L.) fruit is highly consumed worldwide and contains high amounts of carotenoids and tocopherols, two powerful antioxidants. Native tomato genotypes are rarely used in large-scale market but serve as a reservoir to diversify the species gene pool and can be employed to obtain functional compounds. Extraction methods are currently changing towards cleaner procedures that are more efficient and environmentally friendly, including avoiding toxic or polluting solvents. Experimental approach. In this study, factorial and fractional factorial designs were used to evaluate the efficiency of digestive enzymes, sonication and green solvents to obtain lipophilic antioxidant extracts from native tomato. To monitor the efficiency of the extraction process, spectrophotometric quantification of total carotenoids and antioxidant activity was carried out, and then individual quantification of carotenoids and tocopherols in the extracts was done by HPLC. Results and conclusions. Digestive enzymes and sonication increased the carotenoid content and the antioxidant activity of the obtained extracts when applied individually. However, when these treatments were applied together and in combination with isopropyl acetate, a green solvent, the obtained extracts had the highest carotenoid and tocopherol contents as well as the maximal antioxidant activity. A correlation analysis suggested that antioxidant activity resulted from synergistic effects rather than individual compounds. Tomato extracts were obtained through a rapid and environmentally friendly extraction method and their antioxidant activity was enhanced. Novelty and scientific contribution. Tomato fruits have been the subject of numerous studies; however, functional compound extraction through environmentally friendly methods remains an attractive use of native tomato fruit, enhancing its limited production and harnessing a large amount of tomato product industry. There are few reports where environmentally friendly extraction methods are combined; even rarer are those where green solvents are also used. In this work, the combination of different environmentally friendly extraction methods improved the extraction of carotenoids and tocopherols and allowed to establish a more efficient process. These results could stimulate the use of clean technologies and make the native tomato more attractive for industrial or compound extraction processes.Pozadina istraživanja. Rajčica (Solanum lycopersicum L.) je bogata karotenoidima i tokoferolima, izuzetno jakim antioksidansima, a njezin se plod konzumira diljem svijeta. Nativni se genotipovi rajčica rijetko u većoj mjeri uzgajaju za tržište, već služe kao izvor genske raznolikosti te se mogu koristiti za izolaciju funkcionalnih spojeva. Postupci ekstrakcije su u novije vrijeme usmjereni ka primjeni učinkovitijih i ekološki prihvatljivih metoda koje ne koriste toksična otapala što zagađuju okoliš. Eksperimentalni pristup. U ovom je radu primjenom potpunog i djelomičnog faktorskog plana pokusa ispitan učinak probavnih enzima, ultrazvuka i zelenih otapala na ekstrakciju lipofilnih antioksidansa iz nativnih genotipova rajčica. Za utvrđivanje uspješnosti ekstrakcije spektrofotometrijski su ispitani maseni udjel ukupnih karotenoida u ekstraktima i njihova antioksidacijska aktivnost, a zatim je pomoću metode HPLC određen maseni udjel pojedinih karotenoida i tokoferola u ekstraktima. Rezultati i zaključci. Maseni udjel karotenoida i antioksidacijska aktivnost ekstrakata povećali su se nakon obrade probavnim enzimima ili ultrazvukom, međutim njihovom kombiniranom primjenom uz dodatak izopropil-acetata kao zelenog otapala dobiveni su ekstrakti s najvećim udjelom karotenoida i tokoferola te najvećom antioksidacijskom aktivnosti. Rezultati korelacijske analize pokazuju da je antioksidacijska aktivnost rezultat sinergijskog učinka, a ne djelovanja pojedinog spoja. Ekstrakti rajčice dobiveni su brzim i ekološki prihvatljivim postupkom i njihova se antioksidacijska aktivnost poboljšala. Novina i znanstveni doprinos. Iako je plod rajčice predmet mnogih istraživanja, ekstrakcija funkcionalnih spojeva iz nativnih genotipova rajčica pomoću ekološki prihvatljivih postupaka je naročito zanimljiva jer se njome povećavaju proizvodne mogućnosti i iskorištava velik dio proizvoda industrije rajčica. Dostupan je mali broj radova u kojima su autori koristili kombinaciju različitih ekološki prihvatljivih postupaka ekstrakcije, a još su rjeđa istraživanja u kojima su korištena i zelena otapala. U ovom je radu kombinacijom različitih ekološki prihvatljivih postupaka poboljšana ekstrakcija karotenoida i tokoferola i povećana učinkovitost procesa. Dobiveni rezultati mogu potaknuti primjenu čistih tehnologija i korištenje nativnih genotipova rajčica u industrijskoj proizvodnji ili ekstrakciji spojeva