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1.
PLoS One ; 19(5): e0303833, 2024.
Article in English | MEDLINE | ID: mdl-38768175

ABSTRACT

Fatigue can lead to several health issues and is particularly prevalent among elderly individuals with chronic inflammatory conditions. Ninjin'yoeito, a traditional Japanese herbal medicine, is used to address fatigue and malaise, anorexia, and anemia. This study aimed to examine whether relieving inflammation in the brain and skeletal muscle of senescence-accelerated mice prone 8 (SAMP8) could reduce fatigue-like conditions associated with aging. First, SAMP8 mice were divided into two groups, with and without ninjin'yoeito treatment. The ninjin'yoeito-treated group received a diet containing 3% ninjin'yoeito for a period of 4 months starting at 3 months of age. At 7 months of age, all mice underwent motor function, treadmill fatigue, and behavioral tests. They were then euthanized and the skeletal muscle weight, muscle cross-sectional area, and concentration of interleukin (IL)-1ß and IL-1 receptor antagonist (IL-1RA) in both the brain and skeletal muscle were measured. The results showed that the ninjin'yoeito-treated group had higher motor function and spontaneous locomotor activity than the untreated group did and ran for significantly longer in the treadmill fatigue test. Moreover, larger muscle cross-sectional area, lower IL-1ß concentrations, and higher IL-1RA concentrations were observed in both the brain and skeletal muscle tissues of the ninjin'yoeito-treated group than in the untreated group. The results suggest that ninjin'yoeito improves age-related inflammatory conditions in both the central and peripheral tissues and reduces fatigue.


Subject(s)
Aging , Brain , Drugs, Chinese Herbal , Fatigue , Inflammation , Muscle, Skeletal , Animals , Mice , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Aging/drug effects , Fatigue/drug therapy , Brain/drug effects , Brain/metabolism , Brain/pathology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Male , Inflammation/drug therapy , Inflammation/pathology , Interleukin-1beta/metabolism
2.
Int J Mol Sci ; 25(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731887

ABSTRACT

This study explores olive flounder by-product Prozyme2000P (OFBP) hydrolysate as a potential treatment for age-related kidney decline. Ferroptosis, a form of cell death linked to iron overload and oxidative stress, is increasingly implicated in aging kidneys. We investigated whether OFBP could inhibit ferroptosis and improve kidney health. Using TCMK-1 cells, we found that OFBP treatment protected cells from ferroptosis induced by sodium iodate (SI). OFBP also preserved the mitochondria health and influenced molecules involved in ferroptosis regulation. In aging mice, oral administration of OFBP significantly improved kidney health markers. Microscopic examination revealed reduced thickening and scarring in the kidney's filtering units, a hallmark of aging. These findings suggest that OFBP hydrolysate may be a promising therapeutic candidate for age-related kidney decline. By inhibiting ferroptosis, OFBP treatment appears to improve both cellular and structural markers of kidney health. Further research is needed to understand how OFBP works fully and test its effectiveness in more complex models.


Subject(s)
Ferroptosis , Kidney , Animals , Ferroptosis/drug effects , Mice , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Aging/drug effects , Flounder/metabolism , Oxidative Stress/drug effects , Protein Hydrolysates/pharmacology , Protein Hydrolysates/chemistry , Mitochondria/drug effects , Mitochondria/metabolism , Male , Cell Line , Kidney Diseases/drug therapy , Kidney Diseases/metabolism , Kidney Diseases/pathology
3.
Sci Rep ; 14(1): 11536, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773201

ABSTRACT

Advances in modern medicine have extended human life expectancy, leading to a world with a gradually aging society. Aging refers to a natural decline in the physiological functions of a species over time, such as reduced pain sensitivity and reaction speed. Healthy-level physiological pain serves as a warning signal to the body, helping to avoid noxious stimuli. Physiological pain sensitivity gradually decreases in the elderly, increasing the risk of injury. Therefore, geriatric health care receives growing attention, potentially improving the health status and life quality of the elderly, further reducing medical burden. Health food is a geriatric healthcare choice for the elderly with Ganoderma tsuage (GT), a Reishi type, as the main product in the market. GT contains polysaccharides, triterpenoids, adenosine, immunoregulatory proteins, and other components, including anticancer, blood sugar regulating, antioxidation, antibacterial, antivirus, and liver and stomach damage protective agents. However, its pain perception-related effects remain elusive. This study thus aimed at addressing whether GT could prevent pain sensitivity reduction in the elderly. We used a galactose-induced animal model for aging to evaluate whether GT could maintain pain sensitivity in aging mice undergoing formalin pain test, hot water test, and tail flexes. Our results demonstrated that GT significantly improved the sensitivity and reaction speed to pain in the hot water, hot plate, and formalin tests compared with the control. Therefore, our animal study positions GT as a promising compound for pain sensitivity maintenance during aging.


Subject(s)
Aging , Animals , Mice , Aging/drug effects , Aging/physiology , Male , Pain Threshold/drug effects , Pain/drug therapy , Ganoderma/chemistry , Disease Models, Animal , Pain Measurement
4.
Physiol Meas ; 45(5)2024 May 21.
Article in English | MEDLINE | ID: mdl-38697205

ABSTRACT

Objectives.The purpose of this study is to investigate the age dependence of bilateral frontal electroencephalogram (EEG) coupling characteristics, and find potential age-independent depth of anesthesia monitoring indicators for the elderlies.Approach.We recorded bilateral forehead EEG data from 41 patients (ranged in 19-82 years old), and separated into three age groups: 18-40 years (n= 12); 40-65 years (n= 14), >65 years (n= 15). All these patients underwent desflurane maintained general anesthesia (GA). We analyzed the age-related EEG spectra, phase amplitude coupling (PAC), coherence and phase lag index (PLI) of EEG data in the states of awake, GA, and recovery.Main results.The frontal alpha power shows age dependence in the state of GA maintained by desflurane. Modulation index in slow oscillation-alpha and delta-alpha bands showed age dependence and state dependence in varying degrees, the PAC pattern also became less pronounced with increasing age. In the awake state, the coherence in delta, theta and alpha frequency bands were all significantly higher in the >65 years age group than in the 18-40 years age group (p< 0.05 for three frequency bands). The coherence in alpha-band was significantly enhanced in all age groups in GA (p< 0.01) and then decreased in recovery state. Notably, the PLI in the alpha band was able to significantly distinguish the three states of awake, GA and recovery (p< 0.01) and the results of PLI in delta and theta frequency bands had similar changes to those of coherence.Significance.We found the EEG coupling and synchronization between bilateral forehead are age-dependent. The PAC, coherence and PLI portray this age-dependence. The PLI and coherence based on bilateral frontal EEG functional connectivity measures and PAC based on frontal single-channel are closely associated with anesthesia-induced unconsciousness.


Subject(s)
Desflurane , Electroencephalography , Humans , Desflurane/pharmacology , Adult , Middle Aged , Aged , Electroencephalography/drug effects , Young Adult , Male , Female , Aged, 80 and over , Adolescent , Aging/physiology , Aging/drug effects , Frontal Lobe/drug effects , Frontal Lobe/physiology , Isoflurane/analogs & derivatives , Isoflurane/pharmacology , Anesthetics, Inhalation/pharmacology , Anesthesia, General
5.
Alzheimers Res Ther ; 16(1): 109, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750512

ABSTRACT

BACKGROUND: As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD. METHODS: mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK-/-) mice. Animals' cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation. RESULTS: Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK-/- mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists. CONCLUSIONS: Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.


Subject(s)
Alzheimer Disease , Amnesia, Anterograde , Cholecystokinin , Disease Models, Animal , Mice, Transgenic , Receptor, Cholecystokinin B , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Mice , Receptor, Cholecystokinin B/genetics , Receptor, Cholecystokinin B/agonists , Receptor, Cholecystokinin B/deficiency , Amnesia, Anterograde/drug therapy , Cholecystokinin/metabolism , Entorhinal Cortex/drug effects , Entorhinal Cortex/metabolism , Male , Mice, Knockout , Mice, Inbred C57BL , Long-Term Potentiation/drug effects , Hippocampus/metabolism , Hippocampus/drug effects , Aging/drug effects
6.
J Nanobiotechnology ; 22(1): 252, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750509

ABSTRACT

With increasing proportion of the elderly in the population, age-related diseases (ARD) lead to a considerable healthcare burden to society. Prevention and treatment of ARD can decrease the negative impact of aging and the burden of disease. The aging rate is closely associated with the production of high levels of reactive oxygen species (ROS). ROS-mediated oxidative stress in aging triggers aging-related changes through lipid peroxidation, protein oxidation, and DNA oxidation. Antioxidants can control autoxidation by scavenging free radicals or inhibiting their formation, thereby reducing oxidative stress. Benefiting from significant advances in nanotechnology, a large number of nanomaterials with ROS-scavenging capabilities have been developed. ROS-scavenging nanomaterials can be divided into two categories: nanomaterials as carriers for delivering ROS-scavenging drugs, and nanomaterials themselves with ROS-scavenging activity. This study summarizes the current advances in ROS-scavenging nanomaterials for prevention and treatment of ARD, highlights the potential mechanisms of the nanomaterials used and discusses the challenges and prospects for their applications.


Subject(s)
Aging , Free Radical Scavengers , Nanostructures , Oxidative Stress , Reactive Oxygen Species , Reactive Oxygen Species/metabolism , Humans , Nanostructures/chemistry , Aging/drug effects , Oxidative Stress/drug effects , Animals , Free Radical Scavengers/pharmacology , Free Radical Scavengers/chemistry , Free Radical Scavengers/therapeutic use , Antioxidants/pharmacology , Antioxidants/chemistry
7.
J Oleo Sci ; 73(5): 729-742, 2024.
Article in English | MEDLINE | ID: mdl-38692895

ABSTRACT

Astaxanthin is a keto-based carotenoid mainly obtained from marine organisms, like Haematococcus pluvialis (H. pluvialis). Previous studies indicated the protective effects of Astaxanthin and H. pluvialis on aging related oxidative injury in liver, while the potential mechanisms are largely unknown. In addition, H. pluvialis residue is a by-product after astaxanthin extraction, which is rarely studied and utilized. The present study aimed to compare the effects of astaxanthin, H. pluvialis and H. pluvialis residue on the oxidant injury of liver in D-galactose-induced aging mice and explore the potential mechanisms through gut-liver axis. The results showed that all the three supplements prevented D-galactose-induced tissue injury, oxidative stress and chronic inflammation in liver and improved liver function. Gut microbiota analysis indicated that astaxanthin notably increased fecal levels of Bacteroidetes, unclassified_f__ Lachnospiraceae, norank_f__Lachnospiraceae, norank_f__norank_o__Clostridia_UCG-014, Prevotellaceae_ UCG-001, unclassified_f__Prevotellaceae in D-galactose-fed mice (p < 0.05). Compared to aging mice, H. pluvialis group had higher fecal levels of norank_f__Lachnospiraceae and Lachnospiraceae_UCG-006 (p < 0.05). H. pluvialis residue group displayed higher relative levels of Bacteroidetes, Streptococcus, and Rikenellaceae_RC9_gut_group (p < 0.05). Moreover, the production of fecal microbial metabolites, like SCFAs and LPS was also differently restored by the three supplements. Overall, our results suggest astaxanthin, H. pluvialis and H. pluvialis residue could prevent aging related hepatic injury through gutliver axis and provide evidence for exploiting of H. pluvialis residue as a functional ingredient for the treatment of liver diseases. Future studies are needed to further clarify the effect and mechanism of dominant components of H. pluvialis residue on liver injury, which is expected to provide a reference for the high-value utilization of H. pluvialis resources.


Subject(s)
Aging , Galactose , Gastrointestinal Microbiome , Liver , Oxidative Stress , Xanthophylls , Animals , Male , Mice , Aging/drug effects , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/metabolism , Dietary Supplements , Galactose/pharmacology , Gastrointestinal Microbiome/drug effects , Liver/drug effects , Liver/metabolism , Oxidative Stress/drug effects , Xanthophylls/pharmacology , Xanthophylls/isolation & purification
8.
Reprod Biol Endocrinol ; 22(1): 52, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711160

ABSTRACT

BACKGROUND: Elevated FSH often occurs in women of advanced maternal age (AMA, age ≥ 35) and in infertility patients undergoing controlled ovarian stimulation (COS). There is controversy on whether high endogenous FSH contributes to infertility and whether high exogenous FSH adversely impacts patient pregnancy rates. METHODS: The senescence-accelerated mouse-prone-8 (SAMP8) model of female reproductive aging was employed to assess the separate impacts of age and high FSH activity on the percentages (%) of viable and mature ovulated oocytes recovered after gonadotropin treatment. Young and midlife mice were treated with the FSH analog equine chorionic gonadotropin (eCG) to model both endogenous FSH elevation and exogenous FSH elevation. Previously we showed the activin inhibitor ActRIIB:Fc increases oocyte quality by preventing chromosome and spindle misalignments. Therefore, ActRIIB:Fc treatment was performed in an effort to increase % oocyte viability and % oocyte maturation. RESULTS: The high FSH activity of eCG is ootoxic to ovulatory oocytes, with greater decreases in % viable oocytes in midlife than young mice. High FSH activity of eCG potently inhibits oocyte maturation, decreasing the % of mature oocytes to similar degrees in young and midlife mice. ActRIIB:Fc treatment does not prevent eCG ootoxicity, but it restores most oocyte maturation impeded by eCG. CONCLUSIONS: FSH ootoxicity to ovulatory oocytes and FSH maturation inhibition pose a paradox given the well-known pro-growth and pro-maturation activities of FSH in the earlier stages of oocyte growth. We propose the FOOT Hypothesis ("FSH OoToxicity Hypothesis), that FSH ootoxicity to ovulatory oocytes comprises a new driver of infertility and low pregnancy success rates in DOR women attempting spontaneous pregnancy and in COS/IUI patients, especially AMA women. We speculate that endogenous FSH elevation also contributes to reduced fecundity in these DOR and COS/IUI patients. Restoration of oocyte maturation by ActRIB:Fc suggests that activin suppresses oocyte maturation in vivo. This contrasts with prior studies showing activin A promotes oocyte maturation in vitro. Improved oocyte maturation with agents that decrease endogenous activin activity with high specificity may have therapeutic benefit for COS/IVF patients, COS/IUI patients, and DOR patients attempting spontaneous pregnancies.


Subject(s)
Activin Receptors, Type II , Oocytes , Animals , Female , Oocytes/drug effects , Mice , Activin Receptors, Type II/metabolism , Ovulation/drug effects , Chorionic Gonadotropin/pharmacology , Follicle Stimulating Hormone/blood , Oogenesis/drug effects , Ovulation Induction/methods , Immunoglobulin Fc Fragments/pharmacology , Aging/drug effects , Aging/physiology , Pregnancy , Activins
9.
Clin Interv Aging ; 19: 681-693, 2024.
Article in English | MEDLINE | ID: mdl-38706635

ABSTRACT

Aging and aging-related diseases present a global public health problem. Therefore, the development of efficient anti-aging drugs has become an important area of research. Traditional Chinese medicine is an important complementary and alternative branch of aging-related diseases therapy. Recently, a growing number of studies have revealed that traditional Chinese medicine has a certain delaying effect on the progression of aging and aging-related diseases. Here, we review the progress in research into using traditional Chinese medicine for aging and aging-related diseases (including neurodegenerative diseases, cardiovascular diseases, diabetes, and cancer). Furthermore, we summarize the potential mechanisms of action of traditional Chinese medicine and provide references for further studies on aging and aging-related diseases.


Subject(s)
Aging , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Neoplasms , Neurodegenerative Diseases , Humans , Aging/drug effects , Medicine, Chinese Traditional/methods , Neurodegenerative Diseases/drug therapy , Neoplasms/drug therapy , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Diabetes Mellitus/drug therapy
10.
Acta Derm Venereol ; 104: adv39950, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38751178

ABSTRACT

Pruritus in the elderly, particularly those cases without skin dryness or other identifiable causes, makes treatment challenging due to the lack of evidence regarding the therapeutic effects of antipruritics. This study proposes an age-related alloknesis mouse model for an evaluation system for such cases, and aimed to investigate the effectiveness and mechanisms of action of several drugs commonly used as antipruritics in Japan, utilizing this model. Mice 69-80 weeks old were used as aged mice, and the level of mechanical alloknesis was counted as the number of scratching behaviours in response to innocuous stimuli. Bepotastine, neurotropin, pregabalin, baricitinib, and abrocitinib were used as antipruritics, and yohimbine and methysergide as inhibitors of the descending inhibitory pathway. The findings suggest that mechanical alloknesis in aged mice is a suitable animal model for assessing pruritus in the elderly without xerosis, and pregabalin, neurotropin, baricitinib, and abrocitinib may be effective antipruritics in the elderly through activating both the noradrenergic and serotonergic descending inhibitory pathways. These findings may be useful for the selection of antipruritics for pruritus in the elderly without skin lesions or dryness.


Subject(s)
Antipruritics , Disease Models, Animal , Pruritus , Animals , Pruritus/drug therapy , Antipruritics/pharmacology , Antipruritics/therapeutic use , Chronic Disease , Behavior, Animal/drug effects , Mice , Age Factors , Male , Sulfonamides/pharmacology , Pregabalin/pharmacology , Pregabalin/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Purines/pharmacology , Purines/therapeutic use , Aging/drug effects , Azetidines/pharmacology , Azetidines/therapeutic use
11.
J Integr Neurosci ; 23(4): 86, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38682220

ABSTRACT

Due to the growth of the elderly population, age-related neurological disorders are an increasing problem. Aging begins very gradually and later leads to several neurological issues such as lower neurotransmitter levels, oxidative stress, neuronal inflammation, and continual neuronal loss. These changes might contribute to brain disorders such as Alzheimer's disease (AD), dementia or mild cognitive impairment, and epilepsy and glioma, and can also aggravate these disorders if they were previously present. Momordica charantia (bitter gourd), a member of the Cucurbitaceae family, is a good source of carbohydrates, proteins, vitamins, and minerals. It is used for diabetes and known for its hypoglycemic and antioxidant effects. In this review, we discuss the pharmaceutical effects of M. charantia on age-related neurological disorders. We searched several databases, including PubMed and Google Scholar, using MeSH terms. We searched articles published up until 2022 regardless of publication language. M. charantia is rich in luteolin, which increases acetylcholine in neurons by binding to enzymes in acetylcholine metabolism pathways, including butyrylcholinesterase and acetylcholinesterase. This binding inhibits the hyperphosphorylation of tau protein by restraining its kinase enzyme. Furthermore, this substance can lower serum cholesterol and has multi-target activity in AD and memory loss. M. charantia can also improve memory by decreasing tau protein and it also has potent antioxidant activity and anti-inflammatory effects. This review highlights that M. charantia has effects on many age-related neurological disorders, and can be a cost-effective supplement with minimal side effects.


Subject(s)
Momordica charantia , Momordica charantia/chemistry , Humans , Animals , Aging/drug effects , Aging/physiology , Aging/metabolism , Plant Extracts/pharmacology , Nervous System Diseases/drug therapy , Nervous System Diseases/metabolism
12.
J Agric Food Chem ; 72(19): 10879-10896, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38686994

ABSTRACT

Mammary gland aging is one of the most important problems faced by humans and animals. How to delay mammary gland aging is particularly important. Puerarin is a kind of isoflavone substance extracted from Pueraria lobata, which has anti-inflammatory, antioxidant, and other pharmacological effects. However, the role of puerarin in delaying lipopolysaccharide (LPS)-induced mammary gland aging and its underlying mechanism remains unclear. On the one hand, we found that puerarin could significantly downregulate the expression of senescence-associated secretory phenotype (SASP) and age-related indicators (SA-ß-gal, p53, p21, p16) in mammary glands of mice. In addition, puerarin mainly inhibited the p38MAPK signaling pathway to repair mitochondrial damage and delay mammary gland aging. On the other hand, puerarin could also delay the cellular senescence of mice mammary epithelial cells (mMECs) by targeting gut microbiota and promoting the secretion of gut microbiota metabolites. In conclusion, puerarin could not only directly act on the mMECs but also regulate the gut microbiota, thus, playing a role in delaying the aging of the mammary gland. Based on the above findings, we have discovered a new pathway for puerarin to delay mammary gland aging.


Subject(s)
Aging , Gastrointestinal Microbiome , Isoflavones , Mammary Glands, Animal , p38 Mitogen-Activated Protein Kinases , Isoflavones/pharmacology , Animals , Mice , Gastrointestinal Microbiome/drug effects , Female , Mammary Glands, Animal/metabolism , Mammary Glands, Animal/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/genetics , Aging/drug effects , Humans , Pueraria/chemistry , Bacteria/classification , Bacteria/genetics , Bacteria/drug effects , Bacteria/metabolism , Bacteria/isolation & purification , Signal Transduction/drug effects , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Cellular Senescence/drug effects , MAP Kinase Signaling System/drug effects , Mice, Inbred C57BL
13.
Adv Biol (Weinh) ; 8(5): e2400138, 2024 May.
Article in English | MEDLINE | ID: mdl-38616173

ABSTRACT

Yeast is an excellent model organism for research for regulating aging and lifespan, and the studies have made many contributions to date, including identifying various factors and signaling pathways related to aging and lifespan. More than 20 years have passed since molecular biological perspectives are adopted in this research field, and intracellular factors and signal pathways that control aging and lifespan have evolutionarily conserved from yeast to mammals. Furthermore, these findings have been applied to control the aging and lifespan of various model organisms by adjustment of the nutritional environment, genetic manipulation, and drug treatment using low-molecular weight compounds. Among these, drug treatment is easier than the other methods, and research into drugs that regulate aging and lifespan is consequently expected to become more active. Chronological lifespan, a definition of yeast lifespan, refers to the survival period of a cell population under nondividing conditions. Herein, low-molecular weight compounds are summarized that extend the chronological lifespan of Saccharomyces cerevisiae and Schizosaccharomyces pombe, along with their intracellular functions. The low-molecular weight compounds are also discussed that extend the lifespan of other model organisms. Compounds that have so far only been studied in yeast may soon extend lifespan in other organisms.


Subject(s)
Longevity , Saccharomyces cerevisiae , Schizosaccharomyces , Schizosaccharomyces/drug effects , Schizosaccharomyces/genetics , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/genetics , Longevity/drug effects , Molecular Weight , Signal Transduction/drug effects , Aging/drug effects , Aging/physiology
14.
J Nat Med ; 78(3): 576-589, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38662301

ABSTRACT

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.


Subject(s)
Aging , Diet, High-Fat , Drugs, Chinese Herbal , Obesity , Animals , Obesity/drug therapy , Obesity/metabolism , Mice , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Male , Diet, High-Fat/adverse effects , Aging/drug effects , Humans , Hep G2 Cells , Mice, Inbred C57BL , Uncoupling Protein 1/metabolism , Triglycerides/blood , Triglycerides/metabolism , Plant Extracts/pharmacology , Plant Extracts/chemistry , Aspartate Aminotransferases/blood
16.
Aging (Albany NY) ; 16(7): 5829-5855, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38613792

ABSTRACT

Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. Here we assessed swimming performance as well as survival under thermal and oxidative stress across a nematode genetic diversity test panel to evaluate health effects for three compounds previously studied in the Caenorhabditis Intervention Testing Program and thought to promote longevity in different ways - NP1 (nitrophenyl piperazine-containing compound 1), propyl gallate, and resveratrol. Overall, we find the relationships among median lifespan, oxidative stress resistance, thermotolerance, and mobility vigor to be complex. We show that oxidative stress resistance and thermotolerance vary with compound intervention, genetic background, and age. The effects of tested compounds on swimming locomotion, in contrast, are largely species-specific. In this study, thermotolerance, but not oxidative stress or swimming ability, correlates with lifespan. Notably, some compounds exert strong impact on some health measures without an equally strong impact on lifespan. Our results demonstrate the importance of assessing health and lifespan across genetic backgrounds in the effort to identify reproducible anti-aging interventions, with data underscoring how personalized treatments might be required to optimize health benefits.


Subject(s)
Caenorhabditis elegans , Longevity , Oxidative Stress , Animals , Longevity/drug effects , Longevity/genetics , Oxidative Stress/drug effects , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/genetics , Caenorhabditis elegans/physiology , Resveratrol/pharmacology , Aging/drug effects , Aging/genetics , Genetic Background , Swimming , Piperazines/pharmacology , Stilbenes/pharmacology
17.
Behav Brain Res ; 466: 114978, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38582410

ABSTRACT

PURPOSE: As the elderly population grows, the prevalence of dementia is also rapidly increasing worldwide. Metformin, an antidiabetic drug, has been shown to have ameliorative effects on impaired cognitive functions in experimental models. However, studies have generally used young animals. Additionally, although it has a major role in Alzheimer's disease (AD) and memory, literature information about the effects of metformin on the cholinergic system is limited. In this study, we investigated the effects of metformin on memory in a model of scopolamine-induced memory impairment in aged rats. We also examined the effects of metformin on the cholinergic system, which is very important in cognitive functions. METHODS: Metformin was administered orally to male Wistar rats (20-22 months old) at 100 mg/kg/day for three weeks. Morris water maze (MWM) tests were performed to assess spatial memory. Before the probe test of the MWM test, scopolamine was injected intraperitoneally at a dose of 1 mg/kg. After testing, animals were sacrificed, whole brains were removed, and hippocampus samples were separated for biochemical analysis. RESULTS: Impaired memory associated with scopolamine administration was reversed by metformin. In addition, metformin administration ameliorated scopolamine-induced changes in acetylcholine (ACh) levels, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and choline acetyltransferase (ChAT) activity. CONCLUSION: Our results show that metformin may have protective effects in a scopolamine-induced memory impairment model in aged animals by improving cholinergic function. Metformin shows promise in preventing dementia with its dual cholinesterase inhibition and ChAT activation effect.


Subject(s)
Acetylcholine , Aging , Choline O-Acetyltransferase , Disease Models, Animal , Hippocampus , Memory Disorders , Metformin , Rats, Wistar , Scopolamine , Animals , Metformin/pharmacology , Metformin/administration & dosage , Scopolamine/pharmacology , Male , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Rats , Choline O-Acetyltransferase/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Aging/drug effects , Acetylcholine/metabolism , Acetylcholinesterase/metabolism , Maze Learning/drug effects , Hypoglycemic Agents/pharmacology , Spatial Memory/drug effects
18.
Proc Natl Acad Sci U S A ; 121(18): e2311028121, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38657052

ABSTRACT

Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment. Through high-throughput single-cell RNA sequencing (scRNA-seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA-seq database of age-related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age-related retinal disorders.


Subject(s)
Aging , Catechin , Cellular Senescence , Proanthocyanidins , Retina , Animals , Retina/metabolism , Retina/drug effects , Mice , Proanthocyanidins/pharmacology , Proanthocyanidins/metabolism , Aging/drug effects , Aging/metabolism , Cellular Senescence/drug effects , Catechin/pharmacology , Catechin/metabolism , Catechin/chemistry , Biflavonoids/pharmacology , Senotherapeutics/pharmacology , Mice, Inbred C57BL , Humans , Retinal Diseases/drug therapy , Retinal Diseases/metabolism , Retinal Diseases/pathology
19.
Int J Mol Sci ; 25(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38673801

ABSTRACT

In recent years, marine natural products have become one of the most important resources of novel lead compounds for critical diseases associated with age. Spirulina, a dietary supplement made from blue-green algae (cyanobacteria: scientific name Arthrospira platensis), is particularly rich in phycocyanin, a phycobiliprotein, which accounts for up to 20% of this cyanobacterium's dry weight and is considered responsible for its anti-cancer, anti-inflammatory and antioxidant activities. Although the anti-aging activity of phycocyanin has been investigated, how exactly this compound works against aging remains elusive. The aim of our research is to use the yeast Saccharomyces cerevisiae as a model organism to investigate the anti-aging properties of phycocyanin from A. platensis. Our results show that phycocyanin has a powerful anti-aging effect, greatly extending the chronological life span of yeast cells in a dose-dependent way, as the effect was also pronounced when cells were grown in SD medium under calorie restriction conditions (0.2% glucose). Both ROS and accumulation of dead cells were followed by staining chronologically aged cells with dihydrorhodamine 123 (DHR123) and propidium iodide (PI). Interestingly, we found that most of the aged phycocyanin-treated cells, which were unable to form colonies, were actually ROS+/PI-. Finally, we show that the moment in which phycocyanin is added to the culture does not substantially influence its effectiveness in counteracting chronological aging.


Subject(s)
Phycocyanin , Saccharomyces cerevisiae , Spirulina , Phycocyanin/pharmacology , Spirulina/chemistry , Saccharomyces cerevisiae/drug effects , Reactive Oxygen Species/metabolism , Aging/drug effects , Antioxidants/pharmacology
20.
Biomed Pharmacother ; 174: 116517, 2024 May.
Article in English | MEDLINE | ID: mdl-38574619

ABSTRACT

Age-associated osteosarcopenia is an unresolved syndrome characterized by the concomitant loss of bone (osteopenia) and skeletal muscle (sarcopenia) tissues increasing falls, immobility, morbidity, and mortality. Unbalanced resorption of bone in the remodeling process and excessive protein breakdown, especially fast type II myosin heavy chain (MyHC-II) isoform and myofiber metabolic shift, are the leading causes of bone and muscle deterioration in the elderly, respectively. Equisetum arvense (EQ) is a plant traditionally recommended for many pathological conditions due to its anti-inflammatory properties. Thus, considering that a chronic low-grade inflammatory state predisposes to both osteoporosis and sarcopenia, we tested a standardized hydroalcoholic extract of EQ in in vitro models of muscle atrophy [C2C12 myotubes treated with proinflammatory cytokines (TNFα/IFNγ), excess glucocorticoids (dexamethasone), or the osteokine, receptor activator of nuclear factor kappa-B ligand (RANKL)] and osteoclastogenesis (RAW 264.7 cells treated with RANKL). We found that EQ counteracted myotube atrophy, blunting the activity of several pathways depending on the applied stimulus, and reduced osteoclast formation and activity. By in silico target fishing, IKKB-dependent nuclear factor kappa-B (NF-κB) inhibition emerges as a potential common mechanism underlying EQ's anti-atrophic effects. Consumption of EQ (500 mg/kg/day) by pre-geriatric C57BL/6 mice for 3 months translated into: i) maintenance of muscle mass and performance; ii) restrained myofiber oxidative shift; iii) slowed down age-related modifications in osteoporotic bone, significantly preserving trabecular connectivity density; iv) reduced muscle- and spleen-related inflammation. EQ can preserve muscle functionality and bone remodeling during aging, potentially valuable as a natural treatment for osteosarcopenia.


Subject(s)
Equisetum , Plant Extracts , Sarcopenia , Animals , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Mice , Sarcopenia/drug therapy , Sarcopenia/pathology , RAW 264.7 Cells , Equisetum/chemistry , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/pathology , Muscle Fibers, Skeletal/metabolism , Aging/drug effects , Aging/pathology , Muscular Atrophy/drug therapy , Muscular Atrophy/pathology , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteoclasts/pathology , RANK Ligand/metabolism , NF-kappa B/metabolism , Osteogenesis/drug effects , Anti-Inflammatory Agents/pharmacology
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