Two major causes of human aging include protein misfolding and free radicals. Protein misfolding occurs when proteins which are synthesized by cells do not have the proper amino acid sequence or do not achieve the cor...Two major causes of human aging include protein misfolding and free radicals. Protein misfolding occurs when proteins which are synthesized by cells do not have the proper amino acid sequence or do not achieve the correct three-dimensional configuration to function properly. Peer-reviewed scientific literature explains how these processes contribute to many age-associated diseases. A few examples include cancer, heart disease, dementias including Parkinson’s and Alzheimer’s </span><span style="font-family:Verdana;">diseases, and arthritis. This article reviews how protein misfolding can be slowed and even reversed by appropriate nutrition, potentially slowing and reversing these diseases. One cause of misfolding is mRNA translation occurring too rapidly for proper chaperone binding or protein folding. A second cause is deficiency of amino acids so improper tRNA binding occurs. A third cause is free radicals. They cause mutations promoting misfolding and cancer, and oxidize lipoproteins causing plaque in circulation promoting heart disease and stroke. Nutrients with proven actions will contribute to longer healthspans for our aging population. Healthspan is the number of healthy years before chronic or terminal diseases substantially impair the quality of life. This can be done especially by slowing and reversing these three causes of PM. Niacin, quercetin, EGCG, alpha-lipoic acid, N-acetyl-carnitine, tyrosine and cysteine address protein misfolding. Vitamin C and glutathione trap free radicals. Vitamin K amplifies free radical cancer killing by vitamin C and activates decalcification enzymes which remove calcium deposits in the circulatory system and strengthen bones. Apigenin activates the pathway of caloric restriction and induces cancer cell apoptosis. This article provides citations and explanations of the progress showing new ways to maintain health as we age. For convenience and cost savings, many of these ingredients can be consumed in supplement form, taken twice a day to maintain water-soluble nutrient levels.展开更多
The drugs extending healthspan in clinic have always been searched.Nitazoxanide is an FDA-approved clinical antiprotozoal drug.Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo.Our previous st...The drugs extending healthspan in clinic have always been searched.Nitazoxanide is an FDA-approved clinical antiprotozoal drug.Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo.Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and atherosclerosis.Here,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway.Additionally,both nitazoxanide and tizoxanide improve high glucose-induced shortening of C.elegans lifespan.Nitazoxanide has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.展开更多
Human lifespan and life expectancy have increased worldwide,but the number of years that we spend free of chronic or debilitating disorders,known as healthspan,has not shifted along with increased lifespan.This unfavo...Human lifespan and life expectancy have increased worldwide,but the number of years that we spend free of chronic or debilitating disorders,known as healthspan,has not shifted along with increased lifespan.This unfavourable trend presents a tremendous global social-economical problem.We propose a model of promoting optimal human health with proactive,holistic interventions across the lifespan,which require multi-disciplinary,innovative approaches to research and care.We contend that this is the only hope that we have to face the challenges of population growth and aging,as well as the upward trend in non-communicable disease prevalence.展开更多
At the 2017 Linus Pauling meeting, it was announced that based on metabolomic analysis, vitamin K at levels far above the daily value activates a variety of enzymes that are beneficial. The enzymes have been shown to ...At the 2017 Linus Pauling meeting, it was announced that based on metabolomic analysis, vitamin K at levels far above the daily value activates a variety of enzymes that are beneficial. The enzymes have been shown to remove calcium where it harms our health, deposit it where it benefits bone, may reduce hip fractures, and decrease calcification of the circulatory system, reducing by 50% the risk of heart disease and high blood pressure. Linus Pauling demonstrated that vitamin C can kill cancer cells. One form of vitamin K regenerates vitamin C so that it is even more effective at killing cancer cells. I previously reported a trial that determined an oral dosage of vitamin C that produces a concentration in the bladder able to kill recurring non-invasive muscle carcinoma cells. Nature in 1999 published an article on foods that reduce the risk of cancer. Since then there is additional evidence that nutrients can extend the human healthspan. Other nutrients are effective at reducing the risk of cancer, such as the active ingredient in cruciferous vegetables. These nutrients that reduce the risk of cancer and improve health are GRAS. They are safe and likely to substantially reduce the risk of cancer, heart disease, hip fractures, and other undesirable conditions. While research on treating cancer dominates media attention, pharmaceutical development, and Federal funding, it is likely that people can prevent cancer by consuming nutrients that have been shown to kill human cancer cells.展开更多
Aging and metabolic diseases are intricately linked through bidirectional molecular mechanisms that foster a harmful cycle of physiological decline.This cycle is driven by several key factors,including altered nutrien...Aging and metabolic diseases are intricately linked through bidirectional molecular mechanisms that foster a harmful cycle of physiological decline.This cycle is driven by several key factors,including altered nutrient sensing,mitochondrial dysfunction,cellular senescence,chronic inflammation,epigenetic modifications,circadian rhythm disruptions,and imbalances in the gut microbiota.Emerging interventions targeting this aging-metabolism axis hold significant promise for extending healthspan.These approaches include the use of pharmacological mimetics,senolytics,multi-omics strategies,and microbiome modulation,all of which aim to restore metabolic homeostasis and mitigate age-related pathologies.However,several challenges remain in translating these strategies into clinical practice.These include the need for tissue-specific targeting,ensuring the long-term safety of interventions,and addressing socioeconomic disparities in healthcare access.Future research efforts are focusing on integrating multi-omic technologies,organoid and human cellular models,and developing equitable precision medicine frameworks.These initiatives aim to extend healthspan and reduce the global impact of aging-related metabolic diseases.展开更多
Environmental toxicants have been linked to aging and age-related diseases.The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice,Dro...Environmental toxicants have been linked to aging and age-related diseases.The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice,Drosophila melanogaster,and Caenorhabditis elegans.Meanwhile,the resistance to toxicants was increased in long-lived animals.Here,we show that farnesoid X receptor(FXR)agonist obeticholic acid(OCA),a marketed drug for the treatment of cholestasis,may extend the lifespan and healthspan both in C.elegans and chemical-induced early senescent mice.Furthermore,OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C.elegans.The longevity effects of OCA were attenuated in Fxr^(−/−)mice and Fxr homologous nhr-8 and daf-12 mutant C.elegans.In addition,metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor(PXR),a major nuclear receptor for detoxification regulation,in the liver of mice.Together,our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions,thus,targeting FXR may offer to promote longevity.展开更多
As the elderly population expands,the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial.As an FDA-approved drug for chronic cholestatic liver diseases,tauroursodeoxycholic...As the elderly population expands,the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial.As an FDA-approved drug for chronic cholestatic liver diseases,tauroursodeoxycholic acid(TUDCA),a natural bile acid,offers additional health benefits beyond liver protection.Here,we show that TUDCA extends the lifespan and healthspan of C.elegans.Importantly,oral supplementation of TUDCA improves fitness in old mice,including clinically relevant phenotypes,exercise capacity and cognitive function.Consistently,TUDCA treatment drives broad transcriptional changes correlated with anti-aging characteristics.Mechanistically,we discover that TUDCA targets the chaperone HSP90 to promote its protein refolding activity.This collaboration further alleviates aging-induced endoplasmic reticulum(ER)stress and facilitates protein homeostasis,thus offering resistance to aging.In summary,our findings uncover new molecular links between an endogenous metabolite and protein homeostasis,and propose a novel anti-aging strategy that could improve both lifespan and healthspan.展开更多
The dietary intervention of calorie restriction(CR)is known to have the most profound effects on healthspan and lifespan across several species.In two recent back-to-back articles published in Nature,Qu et al.[1,2]rev...The dietary intervention of calorie restriction(CR)is known to have the most profound effects on healthspan and lifespan across several species.In two recent back-to-back articles published in Nature,Qu et al.[1,2]revealed that lithocholic acid(LCA),a singular secondary bile acid found to be elevated in the serum of calorie-restricted mice,is sufficient to mimic the effects of CR by delaying the onset of age-associated phenotypes in mice,and promoting lifespan extension in nematodes and flies.The authors showed that the anti-ageing effects of LCA are mediated through a conserved mechanism resulting in the activation of the lysosomal adenosine-monophosphate(AMP)-activated protein kinase(AMPK)pathway through the TUB-like protein 3(TULP3)-sirtuin(SIRT)-vacuolar H+-ATPase(v-ATPase)axis tomediate thebenefits of CR.展开更多
文摘Two major causes of human aging include protein misfolding and free radicals. Protein misfolding occurs when proteins which are synthesized by cells do not have the proper amino acid sequence or do not achieve the correct three-dimensional configuration to function properly. Peer-reviewed scientific literature explains how these processes contribute to many age-associated diseases. A few examples include cancer, heart disease, dementias including Parkinson’s and Alzheimer’s </span><span style="font-family:Verdana;">diseases, and arthritis. This article reviews how protein misfolding can be slowed and even reversed by appropriate nutrition, potentially slowing and reversing these diseases. One cause of misfolding is mRNA translation occurring too rapidly for proper chaperone binding or protein folding. A second cause is deficiency of amino acids so improper tRNA binding occurs. A third cause is free radicals. They cause mutations promoting misfolding and cancer, and oxidize lipoproteins causing plaque in circulation promoting heart disease and stroke. Nutrients with proven actions will contribute to longer healthspans for our aging population. Healthspan is the number of healthy years before chronic or terminal diseases substantially impair the quality of life. This can be done especially by slowing and reversing these three causes of PM. Niacin, quercetin, EGCG, alpha-lipoic acid, N-acetyl-carnitine, tyrosine and cysteine address protein misfolding. Vitamin C and glutathione trap free radicals. Vitamin K amplifies free radical cancer killing by vitamin C and activates decalcification enzymes which remove calcium deposits in the circulatory system and strengthen bones. Apigenin activates the pathway of caloric restriction and induces cancer cell apoptosis. This article provides citations and explanations of the progress showing new ways to maintain health as we age. For convenience and cost savings, many of these ingredients can be consumed in supplement form, taken twice a day to maintain water-soluble nutrient levels.
基金supported by the National Natural Science Foundation of China(Nos.82373864 and 82170472).
文摘The drugs extending healthspan in clinic have always been searched.Nitazoxanide is an FDA-approved clinical antiprotozoal drug.Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo.Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and atherosclerosis.Here,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway.Additionally,both nitazoxanide and tizoxanide improve high glucose-induced shortening of C.elegans lifespan.Nitazoxanide has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.
基金supported by the Healthspan Institute Initiative of University of Virginia.
文摘Human lifespan and life expectancy have increased worldwide,but the number of years that we spend free of chronic or debilitating disorders,known as healthspan,has not shifted along with increased lifespan.This unfavourable trend presents a tremendous global social-economical problem.We propose a model of promoting optimal human health with proactive,holistic interventions across the lifespan,which require multi-disciplinary,innovative approaches to research and care.We contend that this is the only hope that we have to face the challenges of population growth and aging,as well as the upward trend in non-communicable disease prevalence.
文摘At the 2017 Linus Pauling meeting, it was announced that based on metabolomic analysis, vitamin K at levels far above the daily value activates a variety of enzymes that are beneficial. The enzymes have been shown to remove calcium where it harms our health, deposit it where it benefits bone, may reduce hip fractures, and decrease calcification of the circulatory system, reducing by 50% the risk of heart disease and high blood pressure. Linus Pauling demonstrated that vitamin C can kill cancer cells. One form of vitamin K regenerates vitamin C so that it is even more effective at killing cancer cells. I previously reported a trial that determined an oral dosage of vitamin C that produces a concentration in the bladder able to kill recurring non-invasive muscle carcinoma cells. Nature in 1999 published an article on foods that reduce the risk of cancer. Since then there is additional evidence that nutrients can extend the human healthspan. Other nutrients are effective at reducing the risk of cancer, such as the active ingredient in cruciferous vegetables. These nutrients that reduce the risk of cancer and improve health are GRAS. They are safe and likely to substantially reduce the risk of cancer, heart disease, hip fractures, and other undesirable conditions. While research on treating cancer dominates media attention, pharmaceutical development, and Federal funding, it is likely that people can prevent cancer by consuming nutrients that have been shown to kill human cancer cells.
基金supported by the National Natural Science Foundation of China(Grant No.82470744)Jiangsu Research Innovation Program for College Graduates(No.KYCX25_3257)+2 种基金Qinglan Project of Jiangsu Province Higher Education,National Key Research and Development Program of China(2023YFF1205103-2)National Natural Science Foundation of China(32170756)Beijing Life Science Academy(2024300CD0050).
文摘Aging and metabolic diseases are intricately linked through bidirectional molecular mechanisms that foster a harmful cycle of physiological decline.This cycle is driven by several key factors,including altered nutrient sensing,mitochondrial dysfunction,cellular senescence,chronic inflammation,epigenetic modifications,circadian rhythm disruptions,and imbalances in the gut microbiota.Emerging interventions targeting this aging-metabolism axis hold significant promise for extending healthspan.These approaches include the use of pharmacological mimetics,senolytics,multi-omics strategies,and microbiome modulation,all of which aim to restore metabolic homeostasis and mitigate age-related pathologies.However,several challenges remain in translating these strategies into clinical practice.These include the need for tissue-specific targeting,ensuring the long-term safety of interventions,and addressing socioeconomic disparities in healthcare access.Future research efforts are focusing on integrating multi-omic technologies,organoid and human cellular models,and developing equitable precision medicine frameworks.These initiatives aim to extend healthspan and reduce the global impact of aging-related metabolic diseases.
基金supported by the National Natural Science Foundation of China(82073951)Cheng Huang and the Fok Ying Tung Education Foundation(171036)to Shengjie Fan.
文摘Environmental toxicants have been linked to aging and age-related diseases.The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice,Drosophila melanogaster,and Caenorhabditis elegans.Meanwhile,the resistance to toxicants was increased in long-lived animals.Here,we show that farnesoid X receptor(FXR)agonist obeticholic acid(OCA),a marketed drug for the treatment of cholestasis,may extend the lifespan and healthspan both in C.elegans and chemical-induced early senescent mice.Furthermore,OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C.elegans.The longevity effects of OCA were attenuated in Fxr^(−/−)mice and Fxr homologous nhr-8 and daf-12 mutant C.elegans.In addition,metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor(PXR),a major nuclear receptor for detoxification regulation,in the liver of mice.Together,our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions,thus,targeting FXR may offer to promote longevity.
基金supported by the Research Foundation of Nanhu Laboratory(NSS2021CI05003)the National Natural Science Foundation of China(82273024 and 82022030)。
文摘As the elderly population expands,the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial.As an FDA-approved drug for chronic cholestatic liver diseases,tauroursodeoxycholic acid(TUDCA),a natural bile acid,offers additional health benefits beyond liver protection.Here,we show that TUDCA extends the lifespan and healthspan of C.elegans.Importantly,oral supplementation of TUDCA improves fitness in old mice,including clinically relevant phenotypes,exercise capacity and cognitive function.Consistently,TUDCA treatment drives broad transcriptional changes correlated with anti-aging characteristics.Mechanistically,we discover that TUDCA targets the chaperone HSP90 to promote its protein refolding activity.This collaboration further alleviates aging-induced endoplasmic reticulum(ER)stress and facilitates protein homeostasis,thus offering resistance to aging.In summary,our findings uncover new molecular links between an endogenous metabolite and protein homeostasis,and propose a novel anti-aging strategy that could improve both lifespan and healthspan.
文摘The dietary intervention of calorie restriction(CR)is known to have the most profound effects on healthspan and lifespan across several species.In two recent back-to-back articles published in Nature,Qu et al.[1,2]revealed that lithocholic acid(LCA),a singular secondary bile acid found to be elevated in the serum of calorie-restricted mice,is sufficient to mimic the effects of CR by delaying the onset of age-associated phenotypes in mice,and promoting lifespan extension in nematodes and flies.The authors showed that the anti-ageing effects of LCA are mediated through a conserved mechanism resulting in the activation of the lysosomal adenosine-monophosphate(AMP)-activated protein kinase(AMPK)pathway through the TUB-like protein 3(TULP3)-sirtuin(SIRT)-vacuolar H+-ATPase(v-ATPase)axis tomediate thebenefits of CR.
