2017;31:679\686. levels and finally improves health span and life span. 34 The mechanisms include anti\inflammatory, inhibiting mTOR, regulating insulin/insulin\like growth factor 1, reducing the production of ROS, and modulating the expression of sirtuins. 35 , 36 Retrospective, epidemiological analyses elucidated that administration of metformin is associated with the improvement of vascular function and reductions in the incidence and mortality of ischemic disease. 37 , 38 The results of metformin treatment in age\related disease are also encouraging, with a wide range of protective roles in cardiovascular disease, cerebrovascular disease, cancer, chronic kidney disease, and neurodegeneration. 37 , 39 3.3. Rapamycin Rapamycin is a macrolide compound and was found to exert its role in immune and anti\proliferation responses. 40 Studies showed that rapamycin binds to FK\506\binding protein 12 and destabilizes and inhibits mTORC1, which is an important molecule regulating various cellular processes. 41 Scientists discovered that inhibition of mTORC1 activity showed a favorable effect on increasing Garcinol the life span and health span in different kinds of species. 42 It was proposed that rapamycin extended the life span by up to 60% and even reversed the changes in vascular function and structure, cognition, cardiac hypertrophy, and immune senescence in aged mice, through both genetic and pharmacological modulation of mTOR signaling. 43 , 44 The current clinical uses of rapamycin may be limited by its adverse effect to some extent, including hyperglycemia and hyperlipidaemia. 45 As an effective anti\vascular aging agent, rapamycin has both advantages and disadvantages and it should be balanced for every individual. 3.4. Nicotinamide adenine dinucleotide and sirtuins Nicotinamide adenine dinucleotide (NAD+), as a cofactor in many key biological processes of cells, is an important mediator of biochemical reactions in the body and an essential molecule in many metabolic pathways. It has been found that the concentration of NAD+ in human tissues gradually decreases with age, and at least decreases by 50%, accompanied by a series of pathological processes, such as chronic inflammation, oxidative stress, DNA damage, and mitochondrial dysfunction. 46 Supplementation of NAD+ and its precursors is beneficial to reduce the occurrence of oxidative stress, increase the regenerative capacity of vascular endothelial cells, and prolong cell life. 24 At the same time, sirtuins are a class of NAD+\dependent deacetylases. Studies have discovered that members of the sirtuin family can reduce mitochondrial oxidative stress, promote angiogenesis, and play an important role Garcinol in vascular disease, Garcinol such as hypertension. 47 , 48 3.5. Berberine Berberine is an isoquinoline alkaloid extracted from various plants, which plays an important role in lowering blood pressure, 49 regulating blood lipids, 50 and controlling blood glucose. 51 It was found that berberine could activate the AMPK\signaling pathway, and inhibit the activity of mTOR to delay cell senescence caused by DNA replication disorder, and also increase antioxidant activity by activating the NRF2\signaling pathway to achieve the effect of longevity extension. 52 3.6. Nucleoside reverse transcriptase inhibitors Nucleoside reverse transcriptase inhibitors (NRTIs) are used in clinical HIV treatment, but can also inhibit open\reading frame\related reverse transcriptase activity of long dispersive elements. 24 Recent studies have found that NRTIs, including lamivudine and stavudine, can lower the level of DNA damage and prolong the life span of Sirtuin6?/? mice, and reduce senescence\related secretory phenotypes and inflammatory responses in older mice. 53 , 54 These findings make NRTIs a new candidate for delaying aging. 3.7. Remote ischemic preconditioning Remote ischemic preconditioning (RIPC) is a safe, noninvasive, simple, and low\cost non\drug device intervention and has been widely used since it was first proposed by Karin Przyklenk in 1999. 55 RIPC is an intrinsic protective phenomenon to protect the vital organs with non\fatal regional ischemia followed by reperfusion, through the involvement of SDF\1, HIF\1, oxidative stress, and apoptotic pathways. 56 Short\term RIPC treatment led to increased levels of brain\derived neurotrophic factor and vascular endothelial growth factor in arterial plasma. 57 A recent study has demonstrated that 1\month RIPC treatment can significantly reduce the blood pressure of patients with mild essential hypertension and improve microvascular endothelial function. 58 RIPC may be a novel alternative or complementary intervention means to protect against vascular aging and endothelial dysfunction. 4.?PERSPECTIVES All disease stems from vessels. Vascular aging is a common basis of various vascular diseases, and the normal structure and function of blood vessels are crucial for keeping the health of the seniors. This review.Lopez\Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. kinase (AMPK) activation and metabolic switch of the microbiome. 32 , 33 A study on mice found that treatment with metformin mimics some of the benefits of calorie restriction, such as increased insulin level of sensitivity and reduced low\denseness lipoprotein and cholesterol levels and finally enhances health span and life span. 34 The mechanisms include anti\inflammatory, inhibiting mTOR, regulating insulin/insulin\like growth element 1, reducing the production of ROS, and modulating the manifestation of sirtuins. 35 , 36 Retrospective, epidemiological analyses elucidated that administration of metformin is definitely associated with the improvement of vascular function and reductions in the incidence and mortality of ischemic disease. 37 , 38 The results of metformin treatment in age\related disease will also be encouraging, with a wide range of protecting roles in cardiovascular disease, cerebrovascular disease, malignancy, chronic kidney disease, and neurodegeneration. 37 , 39 3.3. Rapamycin Rapamycin is definitely a macrolide compound and was found to exert its part in immune and anti\proliferation reactions. 40 Studies showed that rapamycin binds to FK\506\binding protein 12 and destabilizes and inhibits mTORC1, which is an important molecule regulating numerous cellular processes. 41 Scientists discovered that inhibition of mTORC1 activity showed a favorable effect on increasing the life span and health span in different kinds of varieties. 42 It was proposed that rapamycin prolonged the life span by up to 60% and even reversed the changes in vascular function and structure, cognition, cardiac hypertrophy, and immune senescence in aged mice, through both genetic and pharmacological modulation of mTOR signaling. 43 , 44 The current medical uses of rapamycin may be limited by its adverse effect to some extent, including hyperglycemia and hyperlipidaemia. 45 As an effective anti\vascular ageing agent, rapamycin offers both advantages and disadvantages and it should be balanced for each and every individual. 3.4. Nicotinamide adenine dinucleotide and sirtuins Nicotinamide adenine dinucleotide (NAD+), like a cofactor in many key biological processes of cells, is an important mediator of biochemical reactions in the body and an essential molecule in many metabolic pathways. It has been found that the concentration of NAD+ in human being tissues gradually decreases with age, and at least decreases by 50%, accompanied by a series of pathological processes, such as chronic swelling, oxidative stress, DNA damage, and mitochondrial dysfunction. 46 Supplementation of NAD+ and its precursors is beneficial to reduce the event of oxidative stress, increase the regenerative capacity of vascular endothelial cells, and prolong cell existence. 24 At the same time, sirtuins are a class of NAD+\dependent deacetylases. Studies have discovered that members of the sirtuin family can reduce mitochondrial oxidative stress, promote angiogenesis, and play an important part in vascular disease, such as hypertension. 47 , 48 3.5. Berberine Berberine is an isoquinoline alkaloid extracted from numerous plants, which takes on an important part in lowering blood pressure, 49 regulating blood lipids, 50 and controlling blood glucose. 51 It was found that berberine could activate the AMPK\signaling pathway, and inhibit the activity of mTOR to delay cell senescence caused by DNA replication disorder, and also increase antioxidant activity by activating the NRF2\signaling pathway to achieve Garcinol the effect of longevity extension. 52 3.6. Nucleoside reverse transcriptase inhibitors Nucleoside reverse transcriptase inhibitors (NRTIs) are used in medical HIV treatment, but can also inhibit open\reading framework\related reverse transcriptase activity of very long dispersive elements. Rabbit Polyclonal to Collagen V alpha2 24 Recent studies have found that NRTIs, including lamivudine and stavudine, can lower the level of DNA damage and prolong the life span of Sirtuin6?/? mice, and reduce senescence\related secretory phenotypes and inflammatory reactions in older mice. 53 , 54 These findings make NRTIs a new candidate for delaying ageing. 3.7. Remote ischemic preconditioning Remote ischemic preconditioning (RIPC) is definitely a safe, noninvasive, simple, and low\cost non\drug device treatment and has been widely used because it was first proposed by Karin Przyklenk in 1999. 55 RIPC is an intrinsic protecting phenomenon to protect the vital organs with non\fatal regional ischemia followed by reperfusion, through the involvement of SDF\1, HIF\1, oxidative stress, and apoptotic pathways. 56 Short\term RIPC treatment led to increased levels of mind\derived neurotrophic element and vascular endothelial growth factor in arterial plasma. 57 A recent study has shown that 1\month RIPC treatment can significantly reduce the blood pressure of individuals with mild essential hypertension and improve microvascular endothelial function. 58 RIPC may be a novel alternate Garcinol or complementary treatment means to protect against vascular ageing.