bims-longev 2023-01-15 papers

bims-longev

Biomed News

on Longevity

Issue of 2023–01–15
nineteen papers selected by
Andreea Nitescu

Nutrition Strategies Promoting Healthy Aging: From Improvement of Cardiovascular and Brain Health to Prevention of Age-Associated Diseases.
Anti-ageing effects of FDA-approved medicines: a focused review.
Associations of Inflammatory, Metabolic, Malnutrition, and Frailty Indexes with Multimorbidity Incidence and Progression, and Mortality Impact: Singapore Longitudinal Aging Study.
Aging Cell and the growing pains of translational geroscience.
Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age.
Metformin and Its Immune-Mediated Effects in Various Diseases.
Disease-Modifying Effects of Non-Invasive Electroceuticals on β-Amyloid Plaques and Tau Tangles for Alzheimer's Disease.
The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4.
Drugging the epigenome in the age of precision medicine.
Induced pluripotent stem cell-derived and directly reprogrammed neurons to study neurodegenerative diseases: The impact of aging signatures.
Mechanisms and the strategy for remission of type 2 diabetes mellitus.
Effect of garlic extract on markers of lipid metabolism and inflammation in coronary artery disease (CAD) patients: A systematic review and meta-analysis.
Ferroptosis in life: To be or not to be.
Epigenetic aging in adult neurogenesis.
Treatment of Dyslipidemia through Targeted Therapy of Gut Microbiota.
Mitochondrial signalling and homeostasis: from cell biology to neurological disease.
Nutrigenomics in Parkinson's disease: diversity of modulatory actions of polyphenols on epigenetic effects induced by toxins.
A Cocktail of Polyherbal Bioactive Compounds and Regular Mobility Training as Senolytic Approaches in Age-dependent Alzheimer's: the In Silico Analysis, Lifestyle Intervention in Old Age.
Alzheimer's Disease is a Multi-Organ Disorder: It May Already Be Preventable.

Nutrients. 2022 Dec 22. pii: 47. [Epub ahead of print]15(1):

Nutrition Strategies Promoting Healthy Aging: From Improvement of Cardiovascular and Brain Health to Prevention of Age-Associated Diseases.

Monika Fekete, Zsofia Szarvas, Vince Fazekas-Pongor, Agnes Feher, Tamas Csipo, Judit Forrai, Norbert Dosa, Anna Peterfi, Andrea Lehoczki, Stefano Tarantini, Janos Tamas Varga.

   BACKGROUND: An increasing number of studies suggest that diet plays an important role in regulating aging processes and modulates the development of the most important age-related diseases.
OBJECTIVE: The aim of this review is to provide an overview of the relationship between nutrition and critical age-associated diseases.
METHODS: A literature review was conducted to survey recent pre-clinical and clinical findings related to the role of nutritional factors in modulation of fundamental cellular and molecular mechanisms of aging and their role in prevention of the genesis of the diseases of aging.
RESULTS: Studies show that the development of cardiovascular and cerebrovascular diseases, neurodegenerative diseases, cognitive impairment and dementia can be slowed down or prevented by certain diets with anti-aging action. The protective effects of diets, at least in part, may be mediated by their beneficial macro- (protein, fat, carbohydrate) and micronutrient (vitamins, minerals) composition.
CONCLUSIONS: Certain diets, such as the Mediterranean diet, may play a significant role in healthy aging by preventing the onset of certain diseases and by improving the aging process itself. This latter can be strengthened by incorporating fasting elements into the diet. As dietary recommendations change with age, this should be taken into consideration as well, when developing a diet tailored to the needs of elderly individuals. Future and ongoing clinical studies on complex anti-aging dietary interventions translating the results of preclinical investigations are expected to lead to novel nutritional guidelines for older adults in the near future.

Keywords:  aging; geriatric diseases; healthy aging; nutrition; prevention

DOI:  https://doi.org/10.3390/nu15010047
J Basic Clin Physiol Pharmacol. 2023 Jan 13.

Anti-ageing effects of FDA-approved medicines: a focused review.

Koranit Thanapairoje, Supanut Junsiritrakhoon, Surasak Wichaiyo, Mohd Azuraidi Osman, Wasu Supharattanasitthi.

  Ageing is the process generated by senescent cells, free radicals, inflammation and other relevant factors. Ageing contributes to age-related diseases that affect the quality of life. People are interested in anti-ageing intervention and many scientists attempt to search for anti-ageing medicines. This review focused on describing in vivo anti-ageing activity of US-FDA-approved drugs and found that alogliptin, canagliflozin and metformin might produce anti-ageing activity via AMPK activation. Rapamycin and canagliflozin are capable to inhibit mTOR to promote lifespan. Atracurium, carnitine and statins act as DAF-16 activators, which potentially contribute to anti-ageing activity. Hydralazine, lisinopril, rosiglitazone and zidovudine may help stabilize genomic integrity to prolong life expectancy. Other indirect mechanisms, including insulin-lowering effect by acarbose and calcium channel blocking activity by verapamil may also promote longevity. Interestingly, some drugs (i.e., canagliflozin, metformin, rapamycin and acarbose) are likely to demonstrate a lifespan-promoting effect predominantly in male animals. These pre-clinical data might provide mechanistic and phenotypic perspectives to better understand the targets of anti-ageing interventions.

Keywords:  FDA-approved; ageing; anti-ageing; drug; lifespan

DOI:  https://doi.org/10.1515/jbcpp-2022-0242
Gerontology. 2023 Jan 06. 1-12

Associations of Inflammatory, Metabolic, Malnutrition, and Frailty Indexes with Multimorbidity Incidence and Progression, and Mortality Impact: Singapore Longitudinal Aging Study.

Chin Yee Cheong, Philip Yap, Keng Bee Yap, Tze Pin Ng.

   INTRODUCTION: The detection of systemic risk factors aids in the formulation of strategies to prevent multimorbidity and its associated mortality impact. We aimed to determine the associations of inflammatory, metabolic, malnutrition, and frailty indexes with multimorbidity onset and progression and their predictions of multimorbidity-associated mortality risk.
METHODS: A prospective cohort study (Singapore Longitudinal Aging Study [SLAS]) of 5,089 community-dwelling older adults aged ≥55 years in two waves of recruitment (SLAS-1: March 2005-September 2007, SLAS-2: January 2013-August 2018). Baseline variables included inflammatory (neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR)) and metabolic profiles (atherogenic index of plasma (AIP), triglyceride-glucose index of insulin resistance (TyG)), physical frailty, and nutritional risk (Mini Nutritional Assessment-Short Form (MNA-SF), Nutritional Screening Initiative (NSI), Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA)). At follow-up, 3-5 years after the baseline interview, incident multimorbidity (≥2 chronic diseases) was determined among multimorbidity-free participants (N = 1,657) and worsening multimorbidity (increase of ≥2 chronic diseases) among participants with baseline multimorbidity (N = 1,207). Mortality in all participants and those with multimorbidity (N = 2,291) was determined up to 31 December, 2016. Odds ratio (OR), hazard ratio (HR), and 95% confidence intervals (95% CI) were estimated in multivariate logistic and Cox regression models, in base model adjustments for age, sex, ethnicity, housing type, smoking, and a number of comorbidities, and further stepwise selection adjustment for other systemic risk indexes.
RESULTS: At baseline, NLR, LMR, AIP, TyG, physical frailty, ENIGMA, NSI, and MNA-SF were significantly associated with prevalent multimorbidity (p < 0.001). Among multimorbidity-free participants, LMR, TyG, and ENIGMA were significantly associated with incident multimorbidity in both the base model and further stepwise selection models: LMR (OR = 0.87, 95% CI: 0.81-0.94), TyG (OR = 1.36, 95% CI: 1.06-1.75), and ENIGMA (OR = 1.15, 95% CI: 1.02-1.30). Among participants with baseline multimorbidity, NLR, LMR, and TyG significantly predicted worsened multimorbidity at follow-up in base model analysis, and LMR (OR = 0.72, 95% CI: 0.60-0.86) and TyG (OR = 1.96, 95% CI: 1.24-3.09) remained as independent predictors in further stepwise selection models. Among participants with prevalent multimorbidity, NLR, TyG, frailty, MNA, and ENIGMA were significantly associated with mortality risk with base model adjustments and further stepwise selection models: NLR (HR = 1.20, 95% CI: 1.10-1.32), TyG (HR = 1.27, 95% CI: 1.04-1.54), frailty (HR = 1.22, 95% CI: 1.10-1.36), ENIGMA (HR = 1.13, 95% CI: 1.05-1.22), MNA (HR = 0.91, 95% CI: 0.85-0.97). A combined systemic risk index shows increasing quartiles, adjusted for age, sex, housing, and smoking status, significantly predicting mortality risk.
DISCUSSION/CONCLUSION: The onset and progression of multimorbidity and its mortality impact are driven by systemic factors, including inflammation, metabolic dysfunction (insulin resistance), malnutrition, and frailty. The measurement of these systemic factors using simple, inexpensive clinical and blood chemistry tools can help in strategies to prevent and reduce its mortality impact.

Keywords:  Frailty; Inflammation; Insulin resistance; Lipids; Metabolic syndrome; Risk factors

DOI:  https://doi.org/10.1159/000527428
Aging Cell. 2023 Jan;22(1): e13769

Aging Cell and the growing pains of translational geroscience.

Monty Montano.

DOI: https://doi.org/10.1111/acel.13769
Aging Cell. 2023 Jan 13. e13767

Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age.

Md Torikul Islam, Eric Tuday, Shanena Allen, John Kim, Daniel W Trott, William L Holland, Anthony J Donato, Lisa A Lesniewski.

  Aging results in an elevated burden of senescent cells, senescence-associated secretory phenotype (SASP), and tissue infiltration of immune cells contributing to chronic low-grade inflammation and a host of age-related diseases. Recent evidence suggests that the clearance of senescent cells alleviates chronic inflammation and its associated dysfunction and diseases. However, the effect of this intervention on metabolic function in old age remains poorly understood. Here, we demonstrate that dasatinib and quercetin (D&Q) have senolytic effects, reducing age-related increase in senescence-associated β-galactosidase, expression of p16 and p21 gene and P16 protein in perigonadal white adipose tissue (pgWAT; all p ≤ 0.04). This treatment also suppressed age-related increase in the expression of a subset of pro-inflammatory SASP genes (mcp1, tnf-α, il-1α, il-1β, il-6, cxcl2, and cxcl10), crown-like structures, abundance of T cells and macrophages in pgWAT (all p ≤ 0.04). In the liver and skeletal muscle, we did not find a robust effect of D&Q on senescence and inflammatory SASP markers. Although we did not observe an age-related difference in glucose tolerance, D&Q treatment improved fasting blood glucose (p = 0.001) and glucose tolerance (p = 0.007) in old mice that was concomitant with lower hepatic gluconeogenesis. Additionally, D&Q improved insulin-stimulated suppression of plasma NEFAs (p = 0.01), reduced fed and fasted plasma triglycerides (both p ≤ 0.04), and improved systemic lipid tolerance (p = 0.006). Collectively, results from this study suggest that D&Q attenuates adipose tissue inflammation and improves systemic metabolic function in old age. These findings have implications for the development of therapeutic agents to combat metabolic dysfunction and diseases in old age.

Keywords:  aging; dasatinib; immune cells; inflammation; metabolic function; quercetin; senescence; senolytics

DOI:  https://doi.org/10.1111/acel.13767
Int J Mol Sci. 2023 Jan 01. pii: 755. [Epub ahead of print]24(1):

Metformin and Its Immune-Mediated Effects in Various Diseases.

Ichiro Nojima, Jun Wada.

  Metformin has been a long-standing prescribed drug for treatment of type 2 diabetes (T2D) and its beneficial effects on virus infection, autoimmune diseases, aging and cancers are also recognized. Metformin modulates the differentiation and activation of various immune-mediated cells such as CD4+ and CD+8 T cells. The activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1) pathway may be involved in this process. Recent studies using Extracellular Flux Analyzer demonstrated that metformin alters the activities of glycolysis, oxidative phosphorylation (OXPHOS), lipid oxidation, and glutaminolysis, which tightly link to the modulation of cytokine production in CD4+ and CD+8 T cells in various disease states, such as virus infection, autoimmune diseases, aging and cancers.

Keywords:  AMPK; CD8 T cells; OXPHOS; aging; autoimmune disease; cancer; mTORC

DOI:  https://doi.org/10.3390/ijms24010755
Int J Mol Sci. 2022 Dec 30. pii: 679. [Epub ahead of print]24(1):

Disease-Modifying Effects of Non-Invasive Electroceuticals on β-Amyloid Plaques and Tau Tangles for Alzheimer's Disease.

Junsoo Bok, Juchan Ha, Bum Ju Ahn, Yongwoo Jang.

  Electroceuticals refer to various forms of electronic neurostimulators used for therapy. Interdisciplinary advances in medical engineering and science have led to the development of the electroceutical approach, which involves therapeutic agents that specifically target neural circuits, to realize precision therapy for Alzheimer's disease (AD). To date, extensive studies have attempted to elucidate the disease-modifying effects of electroceuticals on areas in the brain of a patient with AD by the use of various physical stimuli, including electric, magnetic, and electromagnetic waves as well as ultrasound. Herein, we review non-invasive stimulatory systems and their effects on β-amyloid plaques and tau tangles, which are pathological molecular markers of AD. Therefore, this review will aid in better understanding the recent technological developments, applicable methods, and therapeutic effects of electronic stimulatory systems, including transcranial direct current stimulation, 40-Hz gamma oscillations, transcranial magnetic stimulation, electromagnetic field stimulation, infrared light stimulation and ionizing radiation therapy, and focused ultrasound for AD.

Keywords:  Alzheimer’s disease; electrical stimulation; electroceutical therapy; electroceuticals; tau tangle; β-amyloid plaque

DOI:  https://doi.org/10.3390/ijms24010679
Diabetes Metab J. 2023 Jan 12.

The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4.

Min-Ji Kim, Ibotombi Singh Sinam, Zerwa Siddique, Jae-Han Jeon, In-Kyu Lee.

  Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.

Keywords:  Metabolic diseases; Mitochondria; Muscular atrophy; Pyruvate dehydrogenase acetyl-transferring kinase; Pyruvate dehydrogenase complex; Sarcopenia

DOI:  https://doi.org/10.4093/dmj.2022.0305
Clin Epigenetics. 2023 Jan 11. 15(1): 6

Drugging the epigenome in the age of precision medicine.

Taylor Feehley, Charles W O'Donnell, John Mendlein, Mahesh Karande, Thomas McCauley.

   BACKGROUND: Modulating the epigenome has long been considered a potential opportunity for therapeutic intervention in numerous disease areas with several approved therapies marketed, primarily for cancer. Despite the overall promise of early approaches, however, these drugs have been plagued by poor pharmacokinetic and safety/tolerability profiles due in large part to off-target effects and a lack of specificity.
RESULTS: Recently, there has been marked progress in the field on a new generation of epigenomic therapies which address these challenges directly by targeting defined loci with highly precise, durable, and tunable approaches. Here, we review the promise and pitfalls of epigenetic drug development to date and provide an outlook on recent advances and their promise for future therapeutic applications.
CONCLUSIONS: Novel therapeutic modalities leveraging epigenetics and epigenomics with increased precision are well positioned to advance the field and treat patients across disease areas in the coming years.

Keywords:  Epigenetics; Epigenomics; Precision; Specificity; Therapeutics

DOI:  https://doi.org/10.1186/s13148-022-01419-z
Front Aging Neurosci. 2022 ;14 1069482

Induced pluripotent stem cell-derived and directly reprogrammed neurons to study neurodegenerative diseases: The impact of aging signatures.

Simona Aversano, Carmen Caiazza, Massimiliano Caiazzo.

  Many diseases of the central nervous system are age-associated and do not directly result from genetic mutations. These include late-onset neurodegenerative diseases (NDDs), which represent a challenge for biomedical research and drug development due to the impossibility to access to viable human brain specimens. Advancements in reprogramming technologies have allowed to obtain neurons from induced pluripotent stem cells (iPSCs) or directly from somatic cells (iNs), leading to the generation of better models to understand the molecular mechanisms and design of new drugs. Nevertheless, iPSC technology faces some limitations due to reprogramming-associated cellular rejuvenation which resets the aging hallmarks of donor cells. Given the prominent role of aging for the development and manifestation of late-onset NDDs, this suggests that this approach is not the most suitable to accurately model age-related diseases. Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows the possibility to generate patient-derived neurons that maintain aging and epigenetic signatures of the donor. This aspect may be advantageous for investigating the role of aging in neurodegeneration and for finely dissecting underlying pathological mechanisms. Here, we will compare iPSC and iN models as regards the aging status and explore how this difference is reported to affect the phenotype of NDD in vitro models.

Keywords:  ALS; Alzheimer’s disease; Huntington’s disease; Parkinson’ disease; cell reprogramming; in vitro model

DOI:  https://doi.org/10.3389/fnagi.2022.1069482
J Diabetes Investig. 2023 Jan 10.

Mechanisms and the strategy for remission of type 2 diabetes mellitus.

Tien-Jyun Chang.

Type 2 diabetes is no longer seen as being an irreversible natural course, accompanied by progressive beta cell failure and various chronic diabetes related complications. In contrast, remission can be achieved through a personalized approach. It is a paradigm shift in our understanding of type 2 diabetes and it may be necessary to change the concept of type 2 diabetes as an urgent condition requiring rapid intervention rather than a chronic progressive disease.

DOI: https://doi.org/10.1111/jdi.13948
Phytother Res. 2023 Jan 14.

Effect of garlic extract on markers of lipid metabolism and inflammation in coronary artery disease (CAD) patients: A systematic review and meta-analysis.

Sai Kumar Gadidala, Ebin Johny, Christy Thomas, Mounika Nadella, Krishna Undela, Ramu Adela.

  Several preclinical studies have focused on the beneficial effects of garlic on cardiovascular diseases, but the results were inconsistent. We performed a systematic review and meta-analysis on the effect of garlic powder tablets and aged garlic extract (AGE) in CAD patients, mainly focusing on blood pressure, coronary artery calcification, lipid profile, and inflammatory markers. We searched PubMed, Cochrane CENTRAL, and Google Scholar to identify randomized controlled trials which examined garlic's effect on CAD patients. The standardized mean difference with 95% CI was calculated using fixed-effect or random-effect models. Garlic has shown statistically significant changes of HDL (SMD = 0.18; 95% CI = -0.00 to 0.37; p = .05); LDL (SMD = -0.27; 95% CI = -0.46 to -0.08; p = .004), apolipoprotein-A (SMD = 0.68; 95% CI = 0.24 1.13; p = .002), C-RP (SMD = -0.59; 95% CI = -0.92 to -0.25; p = .0007), IL-6 (SMD = -1.08; 95% CI = -2.17 to 0.01; p = .05), homocysteine (SMD = -0.66; 95% CI = -1.04 to -0.28; p = .0007) and CAC score (SMD = -1.61; 95% CI = -2.66 to -0.57; p = .003). In the case of subgroup analysis, the overall effect was significantly effective in reducing TC, LDL levels and improving HDL levels in CV risk patients. Our study findings provide consistent evidence that intake of garlic reduces CVD risk factors. However, garlic could be considered a safe natural medicine to debilitate inflammation in CAD patients.

Keywords:  coronary artery disease; garlic extract; high-density lipoproteins; low-density lipoproteins

DOI:  https://doi.org/10.1002/ptr.7729
Biomed Pharmacother. 2023 Jan 10. pii: S0753-3322(23)00029-X. [Epub ahead of print]159 114241

Ferroptosis in life: To be or not to be.

Ling Xu, Yu'e Liu, Xi Chen, Hua Zhong, Yi Wang.

  Ferroptosis is a novel type of programmed cell death, characterized by a dysregulated iron metabolism and accumulation of lipid peroxides. It features the alteration of mitochondria and aberrant accumulation of excessive iron as well as loss of the cysteine-glutathione-GPX4 axis. Eventually, the accumulated lipid peroxides result in lethal damage to the cells. Ferroptosis is induced by the overloading of iron and the accumulation of ROS and can be inhibited by the activation of the GPX4 pathway, FS1-CoQ10 pathway, GCH1-BH4 pathway, and the DHODH pathway, it is also regulated by the oncogenes and tumor suppressors. Ferroptosis involves various physiological and pathological processes, and increasing evidence indicates that ferroptosis play a critical role in cancers and other diseases. It inhibits the proliferation of malignant cells in various types of cancers and inducing ferroptosis may become a new method of cancer treatment. Many inhibitors targeting the key factors of ferroptosis such as SLC7A11, GPX4, and iron overload have been developed. The application of ferroptosis is mainly divided into two directions, i.e. to avoid ferroptosis in healthy cells and selectively induce ferroptosis in cancers. In this review, we provide a critical analysis of the concept, and regulation pathways of ferroptosis and explored its roles in various diseases, we also summarized the compounds targeting ferroptosis, aiming to promote the speed of clinical use of ferroptosis induction in cancer treatment.

Keywords:  Cell death; Ferroptosis; GPX4; SLC7A11

DOI:  https://doi.org/10.1016/j.biopha.2023.114241
Hippocampus. 2023 Jan 09.

Epigenetic aging in adult neurogenesis.

Sara Zocher, Tomohisa Toda.

  Neural stem cells (NSCs) in the hippocampus generate new neurons throughout life, which functionally contribute to cognitive flexibility and mood regulation. Yet adult hippocampal neurogenesis substantially declines with age and age-related impairments in NSC activity underlie this reduction. Particularly, increased NSC quiescence and consequently reduced NSC proliferation are considered to be major drivers of the low neurogenesis levels in the aged brain. Epigenetic regulators control the gene expression programs underlying NSC quiescence, proliferation and differentiation and are hence critical to the regulation of adult neurogenesis. Epigenetic alterations have also emerged as central hallmarks of aging, and recent studies suggest the deterioration of the NSC-specific epigenetic landscape as a driver of the age-dependent decline in adult neurogenesis. In this review, we summarize the recently accumulating evidence for a role of epigenetic dysregulation in NSC aging and propose perspectives for future research directions.

Keywords:  DNA methylation; Lamin B1; aging; chromatin; epigenetic; hippocampus; histone; neural stem cells; neurogenesis

DOI:  https://doi.org/10.1002/hipo.23494
Nutrients. 2023 Jan 02. pii: 228. [Epub ahead of print]15(1):

Treatment of Dyslipidemia through Targeted Therapy of Gut Microbiota.

Brandon Flaig, Rachel Garza, Bhavdeep Singh, Sevag Hamamah, Mihai Covasa.

  Dyslipidemia is a multifaceted condition with various genetic and environmental factors contributing to its pathogenesis. Further, this condition represents an important risk factor for its related sequalae including cardiovascular diseases (CVD) such as coronary artery disease (CAD) and stroke. Emerging evidence has shown that gut microbiota and their metabolites can worsen or protect against the development of dyslipidemia. Although there are currently numerous treatment modalities available including lifestyle modification and pharmacologic interventions, there has been promising research on dyslipidemia that involves the benefits of modulating gut microbiota in treating alterations in lipid metabolism. In this review, we examine the relationship between gut microbiota and dyslipidemia, the impact of gut microbiota metabolites on the development of dyslipidemia, and the current research on dietary interventions, prebiotics, probiotics, synbiotics and microbiota transplant as therapeutic modalities in prevention of cardiovascular disease. Overall, understanding the mechanisms by which gut microbiota and their metabolites affect dyslipidemia progression will help develop more precise therapeutic targets to optimize lipid metabolism.

Keywords:  Akkermansia muciniphila; Fecalibacterium prausnitszii; fecal microbiota transplantation; folate; mediterranean diet; prebiotics; probiotics; synbiotics

DOI:  https://doi.org/10.3390/nu15010228
Trends Neurosci. 2023 Jan 10. pii: S0166-2236(22)00239-9. [Epub ahead of print]

Mitochondrial signalling and homeostasis: from cell biology to neurological disease.

Jack J Collier, Monika Oláhová, Thomas G McWilliams, Robert W Taylor.

  Efforts to understand how mitochondrial dysfunction contributes to neurodegeneration have primarily focussed on the role of mitochondria in neuronal energy metabolism. However, progress in understanding the etiological nature of emerging mitochondrial functions has yielded new ideas about the mitochondrial basis of neurological disease. Studies aimed at deciphering how mitochondria signal through interorganellar contacts, vesicular trafficking, and metabolic transmission have revealed that mitochondrial regulation of immunometabolism, cell death, organelle dynamics, and neuroimmune interplay are critical determinants of neural health. Moreover, the homeostatic mechanisms that exist to protect mitochondrial health through turnover via nanoscale proteostasis and lysosomal degradation have become integrated within mitochondrial signalling pathways to support metabolic plasticity and stress responses in the nervous system. This review highlights how these distinct mitochondrial pathways converge to influence neurological health and contribute to disease pathology.

Keywords:  immunity; inflammation; metabolism; mitochondrial-derived vesicles; mitochondria–lysosome axis; quality control

DOI:  https://doi.org/10.1016/j.tins.2022.12.001
Nutr Neurosci. 2023 Jan;26(1): 72-84

Nutrigenomics in Parkinson's disease: diversity of modulatory actions of polyphenols on epigenetic effects induced by toxins.

Moara Rodrigues-Costa, Matheus Santos de Sousa Fernandes, Gabriela Carvalho Jurema-Santos, Lílian Vanessa da Penha Gonçalves, Belmira Lara da Silveira Andrade-da-Costa.

  Although the pathogenesis of Parkinson's Disease (PD) is not completely understood, there is a consensus that it can be caused by multifactorial mechanisms involving genetic susceptibility, epigenetic modifications induced by toxins and mitochondrial dysfunction. In the past 20 years, great efforts have been made in order to clarify molecular mechanisms that are risk factors for this disease, as well as to identify bioactive agents for prevention and slowing down of its progression. Nutraceutical products have received substantial interest due to their nutritional, safe and therapeutic effects on several chronic diseases. The aim of this review was to gather the main evidence of the epigenetic mechanisms involved in the neuroprotective effects of phenolic compounds currently under investigation for the treatment of toxin-induced PD. These studies confirm that the neuroprotective actions of polyphenols involve complex epigenetic modulations, demonstrating that the intake of these natural compounds can be a promising, low-cost, pharmacogenomic strategy against the development of PD.

Keywords:  DNA methyltransferase inhibitors/activators; Epigenetic modulation; Phenolic compounds; histone acetyltransferase activators/inhibitors; histone deacetylase inhibitors; neuroprotection; non-coding RNAs; pesticides

DOI:  https://doi.org/10.1080/1028415X.2021.2017662
J Mol Neurosci. 2023 Jan 12.

A Cocktail of Polyherbal Bioactive Compounds and Regular Mobility Training as Senolytic Approaches in Age-dependent Alzheimer's: the In Silico Analysis, Lifestyle Intervention in Old Age.

Fatemeh Hajibabaie, Navid Abedpoor, Farzaneh Taghian, Kamran Safavi.

  Alzheimer's is a principal concern globally. Machine learning is a valuable tool to determine protective and diagnostic approaches for the elderly. We analyzed microarray datasets of Alzheimer's cases based on artificial intelligence by R statistical software. This study provided a screened pool of ncRNAs and coding RNAs related to Alzheimer's development. We designed hub genes as cut points in networks and predicted potential microRNAs and LncRNA to regulate protein networks in aging and Alzheimer's through in silico algorithms. Notably, we collected effective traditional herbal medicines. A list of bioactive compounds prepared including capsaicin, piperine, crocetin, safranal, saffron oil, coumarin, thujone, rosmarinic acid, sabinene, thymoquinone, ascorbic acid, vitamin E, cyanidin, rhaponticin, isovitexin, coumarin, nobiletin, evodiamine, gingerol, curcumin, quercetin, fisetin, and allicin as an effective fusion that potentially modulates hub proteins and molecular signaling pathways based on pharmacophore model screening and chemoinformatics survey. We identified profiles of 21 mRNAs, 272 microRNAs, and eight LncRNA in Alzheimer's based on prediction algorithms. We suggested a fusion of senolytic herbal ligands as an alternative therapy and preventive formulation in dementia. Also, we provided ncRNAs expression status as novel monitoring strategies in Alzheimer's and new cut-point proteins as novel therapeutic approaches. Synchronizing fusion drugs and lifestyle could reverse Alzheimer's hallmarks to amelioration via an offset of the signaling pathways, leading to increased life quality in the elderly.

Keywords:  Alzheimer’s; Artificial intelligence; Biomedicalinformatics; Chemoinformatics; Herbal medicine; Regular mobility

DOI:  https://doi.org/10.1007/s12031-022-02086-8
J Alzheimers Dis. 2023 Jan 03.

Alzheimer's Disease is a Multi-Organ Disorder: It May Already Be Preventable.

Arnold R Eiser, Tamas Fulop.

  In this commentary, we offer an overview of the several environmental and metabolic factors that have been identified as contributing to the development of Alzheimer's disease (AD). Many of these factors involve extracranial organ systems including immune system dysfunction accompanied by neuroinflammation (inflammaging), gastrointestinal dysbiosis, insulin resistance, and hepatic dysfunction. A variety of microbial factors including mouth flora, viruses, and fungi appear to play a significant role. There is a role for the colonic microbiome becoming dysbiotic and producing toxic metabolites. Declining hepatic function contributes diminished neuronal precursors and reduces toxin elimination. Environmental toxins especially metals play an important role in impairing the blood-brain barrier and acting synergistically with biotoxins and other toxic chemicals. Prevention and treatment of AD appears to require measuring several of these biomarkers and implementing corrective actions regarding such toxicants and correcting metabolic dysfunction at early or preclinical stages of this disorder.

Keywords:  Alzheimer’s disease; biotoxins; dementia; dysbiosis; environmental exposure; metabolism; neuroinflammation

DOI:  https://doi.org/10.3233/JAD-221078