COVID-19 and Senotherapeutics: Any Role for the Naturally-occurring Dipeptide Carnosine?
Hipkiss Alan R*
Aston Research Centre for Healthy Ageing (ARCHA), Aston University, Birmingham, B4 7ET, UK
通讯作者: Correspondence should be addressed to: Dr. Alan R. Hipkiss, Aston Research Centre for Healthy Ageing (ARCHA), Aston University, Birmingham, B4 7ET, UK. Email: alanandjill@lineone.netCorrespondence should be addressed to: Dr. Alan R. Hipkiss, Aston Research Centre for Healthy Ageing (ARCHA), Aston University, Birmingham, B4 7ET, UK. Email: alanandjill@lineone.net
收稿日期:2020-05-15
修回日期: 2020-05-17
接受日期: 2020-05-18
网络出版日期: 2020-07-23
版权声明:
2020 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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Abstract
It is suggested that the non-toxic dipeptide carnosine (beta-alanyl-L-histidine) should be examined as a potential protective agent against COVID-19 infection and inflammatory consequences especially in the elderly. Carnosine is an effective anti-inflammatory agent which can also inhibit CD26 and ACE2 activity. It is also suggested that nasal administration would direct the peptide directly to the lungs and escape the attention of serum carnosinase.
HipkissAlan R. COVID-19 and Senotherapeutics: Any Role for the Naturally-occurring Dipeptide Carnosine?[J]. Aging and Disease, 2020, 11(4): 737-741 https://doi.org/10.14336/AD.2020.0518
It has become clear that, compared to the young, elderly humans are especially susceptible to fatal infection by COVID-19, most likely due, it is thought, to pre-existing, age-related, underlying conditions. Consequently, a number of recent publications [1,2,3.4] have discussed how the processes of ageing might enhance the impact of the COVID-19 virus upon human physiology. Furthermore, it has been proposed that agents which suppress ageing onset and/or development, should be explored for mitigation of COVID-19 toxicity and mortality in the elderly [1,3,4]. Indeed, a search for effective senotherapeutics has considered a range of possible anti-aging agents and the mechanistic routes that might ameliorate age-related change [3]. It is proposed here that the naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) should also be considered as a potential senotherapeutic which may help to suppress COVID-19 toxicity.
Carnosine, aging and COVID-19
There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33].
Carnosine and blood
Another role for carnosine could include beneficial effects in blood. Recent findings suggest that COVID-19 infection can promote in some patients a hyper-coagulatory state, which is associated increased mortality [34]. The glycolytic by-product methylglyoxal (MG) is generated in increased amounts in type-2 diabetics, especially in erythrocytes following high glycemic-index diets [35]. MG is responsible for much post-synthetic protein glycation in diabetics, including the anti-coagulants anti-thrombin III [36] and plasminogen [37], resulting in a hyper-coagulatory state. Given that carnosine can inhibit protein glycation and possibly scavenge MG, the dipeptide might suppress the MG-induced anti-coagulant modification.
Recent studies have shown that carnosine and acetyl-carnosine are present in human blood; carnosine is present in erythrocytes and acetyl-carnosine is mostly in serum; erythrocytes normally contain carnosine and 10-fold less acetyl-carnosine, while the situation is reversed in serum where acetyl-carnosine is the predominant form. Importantly, these levels decline in elderly humans [38] and low levels of acetyl-carnosine are associated with enhanced frailty [39]. Low carnosine levels have also been detected in blood from patients suffering from age-related macular degeneration [40].
It is perhaps interesting to note that carnosine synthesis may be affected by trauma, even in the distant past, which could influence an individual’s blood carnosine and acetyl-carnosine levels. In adults subjected to childhood trauma, the carnosine synthase gene showed increased methylation, which would decrease carnosine synthesis [41]. Childhood trauma has been linked to psychopathology, accelerated aging-related DNA methylation [42] and schizophrenia [43]. Furthermore, erythrocytes from schizophrenics show evidence of increased aging-related protein glycation [44], while dietary carnosine supplementation has been shown to produce beneficial effects in schizophrenics [45], possibly due, in part, to carnosine’s anti-glycating activity [11,12].
Carnosine as a possible senotherapeutic
All the factors outlined above, lead one to suggest that carnosine should be considered as a possible senotherapeutic, acting either prophylactically by helping to suppress the development of an increasingly frail senescent phenotype and/or therapeutically by interfering with COVID-19 infection (given its reported effects on DPP4 and ACE2). Furthermore, carnosine’s anti-inflammatory effects may help suppress post-infection inflammatory response and fibrosis [46]. It may also be significant that loss of a sense of smell frequently accompanies COVID-19 infection [47], and that the olfactory lobe is normally enriched with carnosine [48]. Consequently, it is suggested that the dipeptide is worth exploring for suppression of COVID-19 toxicity in aged humans, especially in subjects already possessing age-related dysfunction.
As noted above, a decreased serum level of acetyl-carnosine (unsusceptible to hydrolysis by serum carnosinase) has recently been noted as an indicator of frailty in elderly humans [39], thus it may be informative if blood levels of acetyl-carnosine and carnosine could be determined in COVID-19 infected patients.
There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell?
Conclusion.
Carnosine has previously been described as enigmatic [57], and the dipeptide has been shown to exert a variety of effects at biochemical and physiological levels resulting in a large number of possible biological functions [58]. Indeed, as aging is multifactorial, any putative anti-aging agent might be expected to be pluripotent in its actions [59]. Thus, carnosine’s cumulative multifunctional activities could result in a physiologically beneficial outcome in COVID-19 infected aged humans. In order to decrease virus-associated mortality, it is suggested that elderly subjects with low blood carnosine and acetyl-carnosine levels should receive exogenous carnosine, administered nasally.
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Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2. Emergency and Similar Future Global Health Threats
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... It has become clear that, compared to the young, elderly humans are especially susceptible to fatal infection by COVID-19, most likely due, it is thought, to pre-existing, age-related, underlying conditions. Consequently, a number of recent publications [1,2,3.4] have discussed how the processes of ageing might enhance the impact of the COVID-19 virus upon human physiology. Furthermore, it has been proposed that agents which suppress ageing onset and/or development, should be explored for mitigation of COVID-19 toxicity and mortality in the elderly [1,3,4]. Indeed, a search for effective senotherapeutics has considered a range of possible anti-aging agents and the mechanistic routes that might ameliorate age-related change [3]. It is proposed here that the naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) should also be considered as a potential senotherapeutic which may help to suppress COVID-19 toxicity. ...
Biomarkers of biological age as predictors of COVID-19 disease severity
0
2020
Geroprotective and Senoremediative Strategies to Reduce the Comorbidity, Infection Rates, Severity, and Lethality in Gerophilic and Gerolavic Infections
2
2020
... It has become clear that, compared to the young, elderly humans are especially susceptible to fatal infection by COVID-19, most likely due, it is thought, to pre-existing, age-related, underlying conditions. Consequently, a number of recent publications [1,2,3.4] have discussed how the processes of ageing might enhance the impact of the COVID-19 virus upon human physiology. Furthermore, it has been proposed that agents which suppress ageing onset and/or development, should be explored for mitigation of COVID-19 toxicity and mortality in the elderly [1,3,4]. Indeed, a search for effective senotherapeutics has considered a range of possible anti-aging agents and the mechanistic routes that might ameliorate age-related change [3]. It is proposed here that the naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) should also be considered as a potential senotherapeutic which may help to suppress COVID-19 toxicity. ...
... ]. Indeed, a search for effective senotherapeutics has considered a range of possible anti-aging agents and the mechanistic routes that might ameliorate age-related change [3]. It is proposed here that the naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) should also be considered as a potential senotherapeutic which may help to suppress COVID-19 toxicity. ...
A geroscience perspective on COVID-19 mortality
1
2020
... It has become clear that, compared to the young, elderly humans are especially susceptible to fatal infection by COVID-19, most likely due, it is thought, to pre-existing, age-related, underlying conditions. Consequently, a number of recent publications [1,2,3.4] have discussed how the processes of ageing might enhance the impact of the COVID-19 virus upon human physiology. Furthermore, it has been proposed that agents which suppress ageing onset and/or development, should be explored for mitigation of COVID-19 toxicity and mortality in the elderly [1,3,4]. Indeed, a search for effective senotherapeutics has considered a range of possible anti-aging agents and the mechanistic routes that might ameliorate age-related change [3]. It is proposed here that the naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) should also be considered as a potential senotherapeutic which may help to suppress COVID-19 toxicity. ...
Retardation of the senescence of cultured human diploid fibroblasts by carnosine
1
1994
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Effect of carnosine and its Trolox-modified derivatives on life span of Drosophila melanogaster
1
2010
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Effect of carnosine on Drosophila melanogaster lifespan
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2002
Elastin Modification by 4-Hydroxynonenal in Hairless Mice Exposed to UV-A. Role in Photoaging and Actinic Elastosis
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2015
Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice
0
2011
Carnosine as a potential anti-senescence drug
1
2000
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Carnosine decreased oxidation and glycation products in serum and liver of high-fat diet and low-dose streptozotocin-induced diabetic rats
2
2017
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
... It is perhaps interesting to note that carnosine synthesis may be affected by trauma, even in the distant past, which could influence an individual’s blood carnosine and acetyl-carnosine levels. In adults subjected to childhood trauma, the carnosine synthase gene showed increased methylation, which would decrease carnosine synthesis [41]. Childhood trauma has been linked to psychopathology, accelerated aging-related DNA methylation [42] and schizophrenia [43]. Furthermore, erythrocytes from schizophrenics show evidence of increased aging-related protein glycation [44], while dietary carnosine supplementation has been shown to produce beneficial effects in schizophrenics [45], possibly due, in part, to carnosine’s anti-glycating activity [11,12]. ...
Antiglycation and anti-oxidant efficiency of carnosine in the plasma and liver of aged rats
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2017
... It is perhaps interesting to note that carnosine synthesis may be affected by trauma, even in the distant past, which could influence an individual’s blood carnosine and acetyl-carnosine levels. In adults subjected to childhood trauma, the carnosine synthase gene showed increased methylation, which would decrease carnosine synthesis [41]. Childhood trauma has been linked to psychopathology, accelerated aging-related DNA methylation [42] and schizophrenia [43]. Furthermore, erythrocytes from schizophrenics show evidence of increased aging-related protein glycation [44], while dietary carnosine supplementation has been shown to produce beneficial effects in schizophrenics [45], possibly due, in part, to carnosine’s anti-glycating activity [11,12]. ...
Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications
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2013
Effects of thermal denaturation on protein glycation
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2002
Carnosine reacts with protein carbonyl groups: another possible role for the anti-ageing peptide?
1
2000
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Fish c-Jun N-Terminal Kinase (JNK) Pathway Is Involved in Bacterial MDP-Induced Intestinal Inflammation
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... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Protective effect of a new hyaluronic acid -carnosine conjugate on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis
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Modulation of Pro-Oxidant and Pro-Inflammatory Activities of M1 Macrophages by the Natural Dipeptide Carnosine
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2020
Prophylactic administration of carnosine and melatonin abates the incidence of apoptosis, inflammation, and DNA damage induced by titanium dioxide nanoparticles in rat livers
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2019
Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1
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2019
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
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... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
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Preventive Effects of Carnosine on Lipopolysaccharide-induced Lung Injury
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2017
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Carnosine exhibits significant antiviral activity against Dengue and Zika virus
1
2019
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Dipeptidyl peptidase IV inhibitory peptides generated in Spanish dry-cured ham
1
2014
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Leucine-glycine and carnosine dipeptides prevent diabetes induced by multiple low-doses of streptozotocin in an experimental model of adult mice
1
2019
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Antioxidant peptides with Angiotensin converting enzyme inhibitory activities and applications for Angiotensin converting enzyme purification
1
2003
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Carnosine and Kidney Diseases: What We Currently Know?
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2020
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
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1
2020
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective
1
2020
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
A Review of Zinc-L-Carnosine and Its Positive Effects on Oral Mucositis, Taste Disorders, and Gastrointestinal Disorders
1
2020
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Zinc and respiratory tract infections: Perspectives for COVID-19 (Review)
1
2020
... There is evidence, first obtained more than 25 years ago, that carnosine delays senescence, extends lifespan and even rejuvenates cultured human lung fibroblasts [5]. Subsequent studies revealed that carnosine (i) can delay ageing and/or related phenomena in some animal models [6-10], (ii) possesses anti-oxidant and anti-glycating activities [11-15], (iii) possesses anti-inflammatory properties [16-20], (iv) is protective towards lung injury [21-23], (v) can decrease the infectivity of RNA viruses Zika, Denge [24] and influenza [25], (vi) is an inhibitor of CD26 (also known and dipeptidyl peptidase IV (DPP4) [26,27] and ACE-2 (angiotensin converting enzyme 2) [28,29], i.e. the cell receptors to which COVID-19 attaches to ensure infection [30,31], (vii) can complex with zinc ions to form polaprezinc [32]; it has been reported that zinc ions can inhibit COVID-19 RNA polymerase thus suppressing viral replication [33]. ...
Coagulopathy in COVID-19
1
2020
... Another role for carnosine could include beneficial effects in blood. Recent findings suggest that COVID-19 infection can promote in some patients a hyper-coagulatory state, which is associated increased mortality [34]. The glycolytic by-product methylglyoxal (MG) is generated in increased amounts in type-2 diabetics, especially in erythrocytes following high glycemic-index diets [35]. MG is responsible for much post-synthetic protein glycation in diabetics, including the anti-coagulants anti-thrombin III [36] and plasminogen [37], resulting in a hyper-coagulatory state. Given that carnosine can inhibit protein glycation and possibly scavenge MG, the dipeptide might suppress the MG-induced anti-coagulant modification. ...
Aging, Alzheimer's Disease and Dysfunctional Glycolysis; Similar Effects of Too Much and Too Little
1
2019
... Another role for carnosine could include beneficial effects in blood. Recent findings suggest that COVID-19 infection can promote in some patients a hyper-coagulatory state, which is associated increased mortality [34]. The glycolytic by-product methylglyoxal (MG) is generated in increased amounts in type-2 diabetics, especially in erythrocytes following high glycemic-index diets [35]. MG is responsible for much post-synthetic protein glycation in diabetics, including the anti-coagulants anti-thrombin III [36] and plasminogen [37], resulting in a hyper-coagulatory state. Given that carnosine can inhibit protein glycation and possibly scavenge MG, the dipeptide might suppress the MG-induced anti-coagulant modification. ...
The hyperglycemic byproduct methylglyoxal impairs anticoagulant activity through covalent adduction of antithrombin III
1
2014
... Another role for carnosine could include beneficial effects in blood. Recent findings suggest that COVID-19 infection can promote in some patients a hyper-coagulatory state, which is associated increased mortality [34]. The glycolytic by-product methylglyoxal (MG) is generated in increased amounts in type-2 diabetics, especially in erythrocytes following high glycemic-index diets [35]. MG is responsible for much post-synthetic protein glycation in diabetics, including the anti-coagulants anti-thrombin III [36] and plasminogen [37], resulting in a hyper-coagulatory state. Given that carnosine can inhibit protein glycation and possibly scavenge MG, the dipeptide might suppress the MG-induced anti-coagulant modification. ...
A practical method to study functional impairment of proteins by glycation and effects of inhibitors using current coagulation/ fibrinolysis reagent kits
1
2003
... Another role for carnosine could include beneficial effects in blood. Recent findings suggest that COVID-19 infection can promote in some patients a hyper-coagulatory state, which is associated increased mortality [34]. The glycolytic by-product methylglyoxal (MG) is generated in increased amounts in type-2 diabetics, especially in erythrocytes following high glycemic-index diets [35]. MG is responsible for much post-synthetic protein glycation in diabetics, including the anti-coagulants anti-thrombin III [36] and plasminogen [37], resulting in a hyper-coagulatory state. Given that carnosine can inhibit protein glycation and possibly scavenge MG, the dipeptide might suppress the MG-induced anti-coagulant modification. ...
Individual variability in human blood metabolites identifies age-related differences
1
2016
... Recent studies have shown that carnosine and acetyl-carnosine are present in human blood; carnosine is present in erythrocytes and acetyl-carnosine is mostly in serum; erythrocytes normally contain carnosine and 10-fold less acetyl-carnosine, while the situation is reversed in serum where acetyl-carnosine is the predominant form. Importantly, these levels decline in elderly humans [38] and low levels of acetyl-carnosine are associated with enhanced frailty [39]. Low carnosine levels have also been detected in blood from patients suffering from age-related macular degeneration [40]. ...
Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility
2
2020
... Recent studies have shown that carnosine and acetyl-carnosine are present in human blood; carnosine is present in erythrocytes and acetyl-carnosine is mostly in serum; erythrocytes normally contain carnosine and 10-fold less acetyl-carnosine, while the situation is reversed in serum where acetyl-carnosine is the predominant form. Importantly, these levels decline in elderly humans [38] and low levels of acetyl-carnosine are associated with enhanced frailty [39]. Low carnosine levels have also been detected in blood from patients suffering from age-related macular degeneration [40]. ...
... As noted above, a decreased serum level of acetyl-carnosine (unsusceptible to hydrolysis by serum carnosinase) has recently been noted as an indicator of frailty in elderly humans [39], thus it may be informative if blood levels of acetyl-carnosine and carnosine could be determined in COVID-19 infected patients. ...
A Plasma Metabolomic Profiling of Exudative Age-Related Macular Degeneration Showing Carnosine and Mitochondrial Deficiencies
1
2020
... Recent studies have shown that carnosine and acetyl-carnosine are present in human blood; carnosine is present in erythrocytes and acetyl-carnosine is mostly in serum; erythrocytes normally contain carnosine and 10-fold less acetyl-carnosine, while the situation is reversed in serum where acetyl-carnosine is the predominant form. Importantly, these levels decline in elderly humans [38] and low levels of acetyl-carnosine are associated with enhanced frailty [39]. Low carnosine levels have also been detected in blood from patients suffering from age-related macular degeneration [40]. ...
A pilot investigation on DNA methylation modifications associated with complex posttraumatic symptoms in elderly traumatized in childhood
1
2017
... It is perhaps interesting to note that carnosine synthesis may be affected by trauma, even in the distant past, which could influence an individual’s blood carnosine and acetyl-carnosine levels. In adults subjected to childhood trauma, the carnosine synthase gene showed increased methylation, which would decrease carnosine synthesis [41]. Childhood trauma has been linked to psychopathology, accelerated aging-related DNA methylation [42] and schizophrenia [43]. Furthermore, erythrocytes from schizophrenics show evidence of increased aging-related protein glycation [44], while dietary carnosine supplementation has been shown to produce beneficial effects in schizophrenics [45], possibly due, in part, to carnosine’s anti-glycating activity [11,12]. ...
Mechanisms linking childhood trauma exposure and psychopathology: a transdiagnostic model of risk and resilience
1
2020
... It is perhaps interesting to note that carnosine synthesis may be affected by trauma, even in the distant past, which could influence an individual’s blood carnosine and acetyl-carnosine levels. In adults subjected to childhood trauma, the carnosine synthase gene showed increased methylation, which would decrease carnosine synthesis [41]. Childhood trauma has been linked to psychopathology, accelerated aging-related DNA methylation [42] and schizophrenia [43]. Furthermore, erythrocytes from schizophrenics show evidence of increased aging-related protein glycation [44], while dietary carnosine supplementation has been shown to produce beneficial effects in schizophrenics [45], possibly due, in part, to carnosine’s anti-glycating activity [11,12]. ...
Genetic liability to schizophrenia is associated with exposure to traumatic events in childhood
1
2020
... It is perhaps interesting to note that carnosine synthesis may be affected by trauma, even in the distant past, which could influence an individual’s blood carnosine and acetyl-carnosine levels. In adults subjected to childhood trauma, the carnosine synthase gene showed increased methylation, which would decrease carnosine synthesis [41]. Childhood trauma has been linked to psychopathology, accelerated aging-related DNA methylation [42] and schizophrenia [43]. Furthermore, erythrocytes from schizophrenics show evidence of increased aging-related protein glycation [44], while dietary carnosine supplementation has been shown to produce beneficial effects in schizophrenics [45], possibly due, in part, to carnosine’s anti-glycating activity [11,12]. ...
Identification of an argpyrimidine-modified protein in human red blood cells from schizophrenic patients: A possible biomarker for diseases involving carbonyl stress
1
2017
... It is perhaps interesting to note that carnosine synthesis may be affected by trauma, even in the distant past, which could influence an individual’s blood carnosine and acetyl-carnosine levels. In adults subjected to childhood trauma, the carnosine synthase gene showed increased methylation, which would decrease carnosine synthesis [41]. Childhood trauma has been linked to psychopathology, accelerated aging-related DNA methylation [42] and schizophrenia [43]. Furthermore, erythrocytes from schizophrenics show evidence of increased aging-related protein glycation [44], while dietary carnosine supplementation has been shown to produce beneficial effects in schizophrenics [45], possibly due, in part, to carnosine’s anti-glycating activity [11,12]. ...
A preliminary, randomized, double-blind, placebo-controlled trial of L-carnosine to improve cognition in schizophrenia
2
2012
... It is perhaps interesting to note that carnosine synthesis may be affected by trauma, even in the distant past, which could influence an individual’s blood carnosine and acetyl-carnosine levels. In adults subjected to childhood trauma, the carnosine synthase gene showed increased methylation, which would decrease carnosine synthesis [41]. Childhood trauma has been linked to psychopathology, accelerated aging-related DNA methylation [42] and schizophrenia [43]. Furthermore, erythrocytes from schizophrenics show evidence of increased aging-related protein glycation [44], while dietary carnosine supplementation has been shown to produce beneficial effects in schizophrenics [45], possibly due, in part, to carnosine’s anti-glycating activity [11,12]. ...
... There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell? ...
An inflammatory profile correlates with decreased frequency of cytotoxic cells in COVID-19
1
2020
... All the factors outlined above, lead one to suggest that carnosine should be considered as a possible senotherapeutic, acting either prophylactically by helping to suppress the development of an increasingly frail senescent phenotype and/or therapeutically by interfering with COVID-19 infection (given its reported effects on DPP4 and ACE2). Furthermore, carnosine’s anti-inflammatory effects may help suppress post-infection inflammatory response and fibrosis [46]. It may also be significant that loss of a sense of smell frequently accompanies COVID-19 infection [47], and that the olfactory lobe is normally enriched with carnosine [48]. Consequently, it is suggested that the dipeptide is worth exploring for suppression of COVID-19 toxicity in aged humans, especially in subjects already possessing age-related dysfunction. ...
Olfactory dysfunction in the COVID-19 outbreak
1
2020
... All the factors outlined above, lead one to suggest that carnosine should be considered as a possible senotherapeutic, acting either prophylactically by helping to suppress the development of an increasingly frail senescent phenotype and/or therapeutically by interfering with COVID-19 infection (given its reported effects on DPP4 and ACE2). Furthermore, carnosine’s anti-inflammatory effects may help suppress post-infection inflammatory response and fibrosis [46]. It may also be significant that loss of a sense of smell frequently accompanies COVID-19 infection [47], and that the olfactory lobe is normally enriched with carnosine [48]. Consequently, it is suggested that the dipeptide is worth exploring for suppression of COVID-19 toxicity in aged humans, especially in subjects already possessing age-related dysfunction. ...
Carnosine-related dipeptides in the mammalian brain
1
1999
... All the factors outlined above, lead one to suggest that carnosine should be considered as a possible senotherapeutic, acting either prophylactically by helping to suppress the development of an increasingly frail senescent phenotype and/or therapeutically by interfering with COVID-19 infection (given its reported effects on DPP4 and ACE2). Furthermore, carnosine’s anti-inflammatory effects may help suppress post-infection inflammatory response and fibrosis [46]. It may also be significant that loss of a sense of smell frequently accompanies COVID-19 infection [47], and that the olfactory lobe is normally enriched with carnosine [48]. Consequently, it is suggested that the dipeptide is worth exploring for suppression of COVID-19 toxicity in aged humans, especially in subjects already possessing age-related dysfunction. ...
Carnosine treatment for gulf war illness: a randomized controlled trial. Version 2
1
2013
... There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell? ...
Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: A systematic review and meta-analysis of randomized controlled trials
1
2020
... There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell? ...
L-carnosine and its Derivatives as New Therapeutic Agents for the Prevention and Treatment of Vascular Complications of Diabetes
1
2020
... There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell? ...
Effects of Anserine/Carnosine Supplementation on Mild Cognitive Impairment with APOE4
1
2019
... There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell? ...
Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders
1
2002
... There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell? ...
L-Carnosine as an Adjunctive Therapy to Risperidone in Children with Autistic Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial
1
2018
... There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell? ...
Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure
1
2015
... There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell? ...
Serum Carnosinase-1 and Albuminuria Rather than the CNDP1 Genotype Correlate with Urinary Carnosinase-1 in Diabetic and Nondiabetic Patients with Chronic Kidney Disease
1
2019
... There have been a number of studies in which dietary supplementation with carnosine has been explored. Beneficial effects have been observed in schizophrenics [45], Gulf War veterans [49], obese humans [50], diabetics [51], elderly human verbal memory [52], autistic children [53,54] and patients with chronic heart failure [55]. Unfortunately, a major problem with oral administration of carnosine is the presence of carnosinase in serum which will destroy the peptide; indeed high carnosinase activity can limit the efficacy of orally administered carnosine towards chronic kidney disease [56]. An alternative approach would be to use nasal delivery, either as an aerosol or in powder form, thus eliminating the serum carnosinase problem and targeting carnosine directly to the lungs. Hopefully this would suppress COVID-19 infectivity via the dipeptide’s inhibitory effects on both ACE2 and MPP4. Moreover, carnosine’s well-recognised anti-inflammatory activity could suppress any excessive inflammatory response following infection. Such an approach may be especially important in frail subjects, exhibiting low levels of acetyl-carnosine (resistant to carnosinase attack). The precise relationship between these two molecules remains to be revealed; for example, is red cell carnosine a precursor of acetyl-carnosine which is then released from the cell? ...
Carnosine and homocarnosine, the forgotten, enigmatic peptides of the brain
1
2005
... Carnosine has previously been described as enigmatic [57], and the dipeptide has been shown to exert a variety of effects at biochemical and physiological levels resulting in a large number of possible biological functions [58]. Indeed, as aging is multifactorial, any putative anti-aging agent might be expected to be pluripotent in its actions [59]. Thus, carnosine’s cumulative multifunctional activities could result in a physiologically beneficial outcome in COVID-19 infected aged humans. In order to decrease virus-associated mortality, it is suggested that elderly subjects with low blood carnosine and acetyl-carnosine levels should receive exogenous carnosine, administered nasally. ...
Therapeutic Potential of Carnosine and Its Derivatives in the Treatment of Human Diseases
1
2020
... Carnosine has previously been described as enigmatic [57], and the dipeptide has been shown to exert a variety of effects at biochemical and physiological levels resulting in a large number of possible biological functions [58]. Indeed, as aging is multifactorial, any putative anti-aging agent might be expected to be pluripotent in its actions [59]. Thus, carnosine’s cumulative multifunctional activities could result in a physiologically beneficial outcome in COVID-19 infected aged humans. In order to decrease virus-associated mortality, it is suggested that elderly subjects with low blood carnosine and acetyl-carnosine levels should receive exogenous carnosine, administered nasally. ...
Carnosine and the processes of ageing
1
2016
... Carnosine has previously been described as enigmatic [57], and the dipeptide has been shown to exert a variety of effects at biochemical and physiological levels resulting in a large number of possible biological functions [58]. Indeed, as aging is multifactorial, any putative anti-aging agent might be expected to be pluripotent in its actions [59]. Thus, carnosine’s cumulative multifunctional activities could result in a physiologically beneficial outcome in COVID-19 infected aged humans. In order to decrease virus-associated mortality, it is suggested that elderly subjects with low blood carnosine and acetyl-carnosine levels should receive exogenous carnosine, administered nasally. ...
