RESUMO
Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.
Assuntos
Envelhecimento , Taurina , Animais , Humanos , Camundongos , Envelhecimento/sangue , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Senescência Celular , Haplorrinos , Longevidade/efeitos dos fármacos , Longevidade/fisiologia , Taurina/sangue , Taurina/deficiência , Taurina/farmacologia , Suplementos Nutricionais , Dano ao DNA/efeitos dos fármacos , Telomerase/metabolismoRESUMO
Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15-20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. Migration of T cells and parasite-infected RBCs (pRBCs) into the brain are both necessary to precipitate the disease. We have been able to simultaneously target both these parameters of ECM. Curcumin alone was able to reverse all the parameters investigated in this study that govern inflammatory responses, CD8(+) T cell and pRBC sequestration into the brain and blood brain barrier (BBB) breakdown. But the animals eventually died of anemia due to parasite build-up in blood. However, arteether-curcumin (AC) combination therapy even after the onset of symptoms provided complete cure. AC treatment is a promising therapeutic option for HCM.
Assuntos
Encéfalo/parasitologia , Curcumina/uso terapêutico , Eritrócitos/parasitologia , Malária Cerebral/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Animais , Artemisininas/uso terapêutico , Modelos Animais de Doenças , Quimioterapia Combinada , Encefalite/tratamento farmacológico , Eritrócitos/efeitos dos fármacos , Malária Cerebral/parasitologia , CamundongosRESUMO
BACKGROUND: Angiotensin II (Ang II) and high-fat diet are implicated in causing pathological changes in the vascular endothelium, brain, kidney and liver. The association of aneurysm leading to histopathological changes in the splenic compartment remains elusive. Further, the salubrious credentials of antioxidants, especially α-tocopherol and ß-carotene in the resolution of splenic pathology have not been investigated. METHODS: Four-month-old Apoe(-/-) mice were used in the induction of aneurysm by infusing Ang II, and subsequently were orally administered with α-tocopherol and ß-carotene-enriched diet for 60 days. RESULTS: We observed splenomegaly in Ang II-infused aneurysm and high-fat diet-supplemented mice as compared to normal mice. These observations were further confirmed through histopathological investigations, demonstrating splenic follicular hypertrophy. We observed a remarkable decrease in the size of spleen in α-tocopherol and ß-carotene-treated Apoe(-/-) mice as compared with Ang II-treated animals. Furthermore, no marked changes in the histopathological splenic sections were seen in the ß-carotene-treated group. However, hyperplasia and proliferation of immature lymphocytes in the follicles were observed in the α-tocopherol-treated animals. We found that CD4+ T-cell levels were increased in the high-fat diet group relative to the control group and were decreased in the ß-carotene-treated animals. CONCLUSIONS: Our study provides evidence that Ang II infusion and high-fat supplementation induces abdominal aortic aneurysm that has pathological implications to the spleen. The use of ß-carotene but not α-tocopherol as an antioxidant markedly ameliorates the pathological changes in spleen.
Assuntos
Angiotensina II/toxicidade , Aneurisma da Aorta Abdominal/etiologia , Dieta Hiperlipídica/efeitos adversos , Esplenomegalia/etiologia , Vasoconstritores/toxicidade , Animais , Antioxidantes/farmacologia , Apolipoproteínas E/deficiência , Suplementos Nutricionais/efeitos adversos , Masculino , Camundongos Knockout , Linfócitos T/fisiologia , alfa-Tocoferol/farmacologia , beta Caroteno/farmacologiaRESUMO
Abdominal aortic aneurysm (AAA) is a common chronic degenerative disease characterized by progressive aortic dilation and rupture. The mechanisms underlying the role of α-tocopherol and ß-carotene on AAA have not been comprehensively assessed. We investigated if α-tocopherol and ß-carotene supplementation could attenuate AAA, and studied the underlying mechanisms utilized by the antioxidants to alleviate AAA. Four-months-old Apoe(-/-) mice were used in the induction of aneurysm by infusion of angiotensin II (Ang II), and were orally administered with α-tocopherol and ß-carotene enriched diet for 60 days. Significant increase of LDL, cholesterol, triglycerides and circulating inflammatory cells was observed in the Ang II-treated animals, and gene expression studies showed that ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9 and MMP-12 were upregulated in the aorta of aneurysm-induced mice. Extensive plaques, aneurysm and diffusion of inflammatory cells into the tunica intima were also noticed. The size of aorta was significantly (Pâ=â0.0002) increased (2.24±0.20 mm) in the aneurysm-induced animals as compared to control mice (1.17±0.06 mm). Interestingly, ß-carotene dramatically controlled the diffusion of macrophages into the aortic tunica intima, and circulation. It also dissolved the formation of atheromatous plaque. Further, ß-carotene significantly decreased the aortic diameter (1.33±0.12 mm) in the aneurysm-induced mice (ß-carotene, Pâ=â0.0002). It also downregulated ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9, MMP-12, PPAR-α and PPAR-γ following treatment. Hence, dietary supplementation of ß-carotene may have a protective function against Ang II-induced AAA by ameliorating macrophage recruitment in Apoe(-/-) mice.