Treatment Of Age-related Diseases Research Articles

The role of biofactors in the prevention and treatment of age-related diseases.

The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age-related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age-related diseases, and ultimately of mortality in the older population. These biofactors can be a cost-effective strategy to prevent or, in some cases, even treat age-related diseases. Examples reviewed herein include omega-3 fatty acids and dietary fiber for the prevention of CVD, α-tocopherol (vitamin E) for the treatment of biopsy-proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α-lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age-related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors, we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature.

Therapeutic Potential for Regulation of the Nuclear Factor Kappa-B Transcription Factor p65 to Prevent Cellular Senescence and Activation of Pro-Inflammatory in Mesenchymal Stem Cells.

Mesenchymal stem cells have an important potential in the treatment of age-related diseases. In the last years, small extracellular vesicles derived from these stem cells have been proposed as cell-free therapies. Cellular senescence and proinflammatory activation are involved in the loss of therapeutic capacity and in the phenomenon called inflamm-aging. The regulators of these two biological processes in mesenchymal stem cells are not well-known. In this study, we found that p65 is activated during cellular senescence and inflammatory activation in human umbilical cord-derived mesenchymal stem cell. To demonstrate the central role of p65 in these two processes, we used small-molecular inhibitors of p65, such as JSH-23, MG-132 and curcumin. We found that the inhibition of p65 prevents the cellular senescence phenotype in human umbilical cord-derived mesenchymal stem cells. Besides, p65 inhibition produced the inactivation of proinflammatory molecules as components of a senescence-associated secretory phenotype (SASP) (interleukin-6 and interleukin-8 (IL-6 and IL-8)). Additionally, we found that the inhibition of p65 prevents the transmission of paracrine senescence between mesenchymal stem cells and the proinflammatory message through small extracellular vesicles. Our work highlights the important role of p65 and its inhibition to restore the loss of functionality of small extracellular vesicles from senescent mesenchymal stem cells and their inflamm-aging signature.

Chemoinformatic Screening for the Selection of Potential Senolytic Compounds from Natural Products.

Cellular senescence is a cellular condition that involves significant changes in gene expression and the arrest of cell proliferation. Recently, it has been suggested in experimental models that the elimination of senescent cells with pharmacological methods delays, prevents, and improves multiple adverse outcomes related to age. In this sense, the so-called senoylitic compounds are a class of drugs that selectively eliminates senescent cells (SCs) and that could be used in order to delay such adverse outcomes. Interestingly, the first senolytic drug (navitoclax) was discovered by using chemoinformatic and network analyses. Thus, in the present study, we searched for novel senolytic compounds through the use of chemoinformatic tools (fingerprinting and network pharmacology) over different chemical databases (InflamNat and BIOFACQUIM) coming from natural products (NPs) that have proven to be quite remarkable for drug development. As a result of screening, we obtained three molecules (hinokitiol, preussomerin C, and tanshinone I) that could be considered senolytic compound candidates since they share similarities in structure with senolytic leads (tunicamycin, ginsenoside Rb1, ABT 737, rapamycin, navitoclax, timosaponin A-III, digoxin, roxithromycin, and azithromycin) and targets involved in senescence pathways with potential use in the treatment of age-related diseases.

Changes in Peripheral Blood Biomarkers with Aging and Neurodegenerative Disorders.

Aging is associated with most neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Determination of peripheral blood biomarkers represents a low invasive approach for tracking early changes in body metabolism during aging. This study addresses a cross-sectional analysis to identify changes in lipid, minerals, and antioxidant capacity as potential biomarkers to the onset of neurodegenerative diseases during aging. A retrospective analysis was performed to determine age-related biomarkers from a clinical sample database. Next, one hundred volunteers between 20-59 (adult) and over 60 years (elderly) were selected for the motor and cognitive tests according to Unified Parkinson's Disease Rating Scale (UPDRS) and Mini-Mental State Examination (MMSE), respectively. Peripheral blood samples were also collected to determine circulating lipids, minerals, and antioxidant capacity. Lipid profile revealed an increase in triglycerides, total, and VLDL Cholesterol. Among the elderlies, HDL was lower than the adult group, particularly in volunteers with severe cognitive decline. Minerals involved in antioxidant defense such as iron, selenium, and manganese were lower in elderly people compared to adults. Catalase activity was also reduced among elderlies with mild cognitive impairment. Here, we show changes in key serum biomarkers correlate with aging and clinical cognitive decline among elderly people. These findings may contribute to the understanding of how biomarkers can be useful for early diagnosis and treatment of aging-related diseases.

A systems pharmacology approach to identify the autophagy-inducing effects of Traditional Persian medicinal plants

Aging is correlated with several complex diseases, including type 2 diabetes, neurodegeneration diseases, and cancer. Identifying the nature of this correlation and treatment of age-related diseases has been a major subject of both modern and traditional medicine. Traditional Persian Medicine (TPM) embodies many prescriptions for the treatment of ARDs. Given that autophagy plays a critical role in antiaging processes, the present study aimed to examine whether the documented effect of plants used in TPM might be relevant to the induction of autophagy? To this end, the TPM-based medicinal herbs used in the treatment of the ARDs were identified from modern and traditional references. The known phytochemicals of these plants were then examined against literature for evidence of having autophagy inducing effects. As a result, several plants were identified to have multiple active ingredients, which indeed regulate the autophagy or its upstream pathways. In addition, gene set enrichment analysis of the identified targets confirmed the collective contribution of the identified targets in autophagy regulating processes. Also, the protein–protein interaction (PPI) network of the targets was reconstructed. Network centrality analysis of the PPI network identified mTOR as the key network hub. Given the well-documented role of mTOR in inhibiting autophagy, our results hence support the hypothesis that the antiaging mechanism of TPM-based medicines might involve autophagy induction. Chemoinformatics study of the phytochemicals using docking and molecular dynamics simulation identified, among other compounds, the cyclo-trijuglone of Juglans regia L. as a potential ATP-competitive inhibitor of mTOR. Our results hence, provide a basis for the study of TPM-based prescriptions using modern tools in the quest for developing synergistic therapies for ARDs.

Polygonum multiflorum Thunb extract extended the lifespan and healthspan of Caenorhabditis elegans via DAF-16/SIR-2.1/SKN-1

Polygonum multiflorum Thunb (PMT), as a traditional Chinese herbal medicine, has been widely used in the prevention and treatment of aging-related diseases, including Alzheimer's disease, Parkinson's disease, hyperlipidemia, atherosclerosis and inflammation. However, the effect of PMT on the lifespan and its molecular mechanisms are still unclear. Here we found that 60% ethanol refined fraction (PMT-E) of Polygonum multiflorum Thunb at 50 μg mL-1, which contained two main bioactive compounds, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) and emodin-8-O-β-D-glucoside (EG), could significantly increase the mean lifespan by 19.82%, delay the age-related decline of phenotypes, enhance stress resistance and reduce ROS accumulation in Caenorhabditis elegans. Moreover, we also found that the mitochondrial membrane potential (ΔΨ) and ATP content of worms treated with 50 μg mL-1 PMT-E were obviously improved. Further mechanistic studies revealed that DAF-16, SIR-2.1 and SKN-1 transcription factors were required for PMT-E-mediated lifespan extension. Finally, we found that PMT-E could significantly inhibit the toxicity induced by β-amyloid (Aβ) in Aβ transgenic worms. Altogether, these findings laid the foundation for the use of Polygonum multiflorum Thunb to treat aging and age-related diseases.

Clinical Research Progress of NRF2 Activators in the Treatment of Age-related Diseases

Oxidation is closely related to the occurrence and development of aging and age-related diseases. NRF2 (Nuclear factor erythroid 2 related factor 2) is a key regulator of oxidative stress, which regulates the expression of antioxidant proteins, detoxification enzymes and various cytoprotective proteins. NRF2 maintains organism redox balance and genome stability, delaying the aging process and the occurrence and development of aging-related diseases. Pharmacological activators of NRF2 has been widely reported in basic research, and has performed well in clinical application research. In this article, we will focus on the latest news in basic and clinical research of NRF2 activators in age related diseases.

The Development of Maillard Reaction, and Advanced Glycation End Product (AGE)-Receptor for AGE (RAGE) Signaling Inhibitors as Novel Therapeutic Strategies for Patients with AGE-Related Diseases.

Advanced glycation end products (AGEs) are generated by nonenzymatic modifications of macromolecules (proteins, lipids, and nucleic acids) by saccharides (glucose, fructose, and pentose) via Maillard reaction. The formed AGE molecules can be catabolized and cleared by glyoxalase I and II in renal proximal tubular cells. AGE-related diseases include physiological aging, neurodegenerative/neuroinflammatory diseases, diabetes mellitus (DM) and its complications, autoimmune/rheumatic inflammatory diseases, bone-degenerative diseases, and chronic renal diseases. AGEs, by binding to receptors for AGE (RAGEs), alter innate and adaptive immune responses to induce inflammation and immunosuppression via the generation of proinflammatory cytokines, reactive oxygen species (ROS), and reactive nitrogen intermediates (RNI). These pathological molecules cause vascular endothelial/smooth muscular/connective tissue-cell and renal mesangial/endothelial/podocytic-cell damage in AGE-related diseases. In the present review, we first focus on the cellular and molecular bases of AGE–RAGE axis signaling pathways in AGE-related diseases. Then, we discuss in detail the modes of action of newly discovered novel biomolecules and phytochemical compounds, such as Maillard reaction and AGE–RAGE signaling inhibitors. These molecules are expected to become the new therapeutic strategies for patients with AGE-related diseases in addition to the traditional hypoglycemic and anti-hypertensive agents. We particularly emphasize the importance of “metabolic memory”, the “French paradox”, and the pharmacokinetics and therapeutic dosing of the effective natural compounds associated with pharmacogenetics in the treatment of AGE-related diseases. Lastly, we propose prospective investigations for solving the enigmas in AGE-mediated pathological effects.

Reversed Senescence of Retinal Pigment Epithelial Cell by Coculture With Embryonic Stem Cell via the TGFβ and PI3K Pathways.

Retinal pigment epithelium (RPE) cellular senescence is an important etiology of age-related macular degeneration (AMD). Aging interventions based on the application of stem cells to delay cellular senescence have shown good prospects in the treatment of age-related diseases. This study aimed to investigate the potential of the embryonic stem cells (ESCs) to reverse the senescence of RPE cells and to elucidate its regulatory mechanism. The hydrogen peroxide (H2O2)-mediated premature and natural passage-mediated replicative senescent RPE cells were directly cocultured with ESCs. The results showed that the proliferative capacity of premature and replicative senescent RPE cells was increased, while the positive rate of senescence-associated galactosidase (SA-β-GAL) staining and levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were decreased. The positive regulatory factors of cellular senescence (p53, p21WAF1/CIP1, p16INK4a) were downregulated, while the negative regulatory factors of cellular senescence (Cyclin A2, Cyclin B1, Cyclin D1) were upregulated. Furthermore, replicative senescent RPE cells entered the S and G2/M phases from the G0/G1 phase. TGFβ (TGFB1, SMAD3, ID1, ID3) and PI3K (PIK3CG, PDK1, PLK1) pathway-related genes were upregulated in premature and replicative senescent RPE cells after ESCs application, respectively. We further treated ESCs-cocultured premature and replicative senescent RPE cells with SB531542 and LY294002 to inhibit the TGFβ and PI3K pathways, respectively, and found that p53, p21WAF1/CIP1 and p16INK4a were upregulated, while Cyclin A2, Cyclin B1, Cyclin D1, TGFβ, and PI3K pathway-related genes were downregulated, accompanied by decreased proliferation and cell cycle transition and increased positive rates of SA-β-GAL staining and levels of ROS and MMP. In conclusion, we demonstrated that ESCs can effectively reverse the senescence of premature and replicative senescent RPE cells by a direct coculture way, which may be achieved by upregulating the TGFβ and PI3K pathways, respectively, providing a basis for establishing a new therapeutic option for AMD.

Regulation of the regenerative activity of dental pulp stem cells from exfoliated deciduous teeth (SHED) of children by TGF-β1 is associated with ALK5/Smad2, TAK1, p38 and MEK/ERK signaling.

Transforming growth factor-β1 (TGF-β1) regulates wound healing/regeneration and aging processes. Dental pulp stem cells from human exfoliated deciduous teeth (SHED) are cell sources for treatment of age-related disorders. We studied the effect of TGF-β1 on SHED and related signaling. SHED were treated with TGF-β1 with/without pretreatment/co-incubation by SB431542, U0126, 5Z-7-oxozeaenol or SB203580. Sircol collagen assay, 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) assay, RT-PCR, western blotting and PathScan phospho-ELISA were used to measure the effects. We found that SHED expressed ALK1, ALK3, ALK5, TGF-RII, betaglycan and endoglin mRNA. TGF-β1 stimulated p-Smad2, p-TAK1, p-ERK, p-p38 and cyclooxygenase-2 (COX-2) protein expression. It enhanced proliferation and collagen content of SHED that were attenuated by SB431542, 5Z-7-oxozeaenol and SB203580, but not U0126. TGF-β1 (0.5-1 ng/ml) stimulated ALP of SHED, whereas 5-10 ng/ml TGF-β1 suppressed ALP. SB431542 reversed the effects of TGF-β1. However, 5Z-7-oxozeaenol, SB203580 and U0126 only reversed the stimulatory effect of TGF-β1 on ALP. Four inhibitors attenuated TGF-β1-induced COX-2 expression. TGF-β1-stimulated TIMP-1 and N-cadherin was inhibited by SB431542 and 5Z-7-oxozeaenol. These results indicate that TGF-β1 affects SHED by differential regulation of ALK5/Smad2/3, TAK1, p38 and MEK/ERK. TGF-β1 and SHED could potentially be used for tissue engineering/regeneration and treatment of age-related diseases.

Potential of Caenorhabditis elegans as an antiaging evaluation model for dietary phytochemicals: A review

Aging is an inevitable process characterized by the accumulation of degenerative damage, leading to serious diseases that affect human health. Studies on aging aim to develop pre-protection or therapies to delay aging and age-related diseases. A preventive approach is preferable to clinical treatment not only to reduce investment but also to alleviate pain in patients. Adjusting daily diet habits to improve the aging condition is a potentially attractive strategy. Fruits and vegetables containing active compounds that can effectively delay the aging process and reduce or inhibit age-related degenerative diseases have been identified. The signaling pathways related to aging in Caenorhabditis elegans are evolutionarily conserved; thus, studying antiaging components by intervening senescence process may contribute to the prevention and treatment of age-related diseases in humans. This review focuses on the effects of food-derived extracts or purified substance on antiaging in nematodes, as well as the underlying mechanisms, on the basis of several major signaling pathways and key regulatory factors in aging. The aim is to provide references for a healthy diet guidance and the development of antiaging nutritional supplements. Finally, challenges in the use of C. elegans as the antiaging evaluation model are discussed, together with the development that potentially inspire novel strategies and research tools.

Protective Effects of Sesamol on Systemic Inflammation and Cognitive Impairment in Aging Mice

Sesamol, a lignan in sesame, possesses several bioactivities, such as antioxidation, anti-inflammation, and neuroprotective capability. In this study, the effects of sesamol on aging-caused cognitive defects are investigated. Twelve-month-old mice were treated with sesamol (0.1%, w/w) as dietary supplementation for 12 weeks. Behavioral tests revealed that sesamol improved aging-associated cognitive impairments. Sesamol decreased aging-induced oxidative stress via suppression of malondialdehyde production and increased antioxidant enzymes. Histological staining showed that sesamol treatment improved aging-induced neuronal damage and synaptic dysfunction in hippocampus. Furthermore, sesamol significantly reduced aging-induced neuroinflammation by inhibiting the microglial overactivation and inflammatory cytokine expressions. Meanwhile, the accumulation of Aβ1-42 was reduced by sesamol treatment. Moreover, sesamol protected the gut barrier integrity and reduced LPS release, which was highly associated with its beneficial effects on behavioral and inflammatory changes. In conclusion, our findings indicated that the use of sesamol is feasible in the treatment of aging-related diseases.

Errors in the management of patients with Alzheimer's disease: analysis of problems and ways of their solution

Epidemiological data show that Alzheimer's disease (AD) is the most common cause of acquired cognitive impairment (CI). At the same time, according to statistics, vascular CI and vascular dementia predominate in Russia, which is mainly due to imperfect diagnosis, when any pathological condition associated with cerebral dysfunction in a patient with vascular risk factors is interpreted as dyscirculatory encephalopathy or chronic brain ischemia. However, this can be asthenoneurotic syndrome, migraine, vestibular dysfunction, and a number of neurodegenerative diseases, the most common condition of which is certainly AD. What is more, the treatment of age-related diseases, with the exception of acute vascular disease, is receiving manifestly inadequate attention. All this leads to the lack of a unified methodology for the management of these patients, to the impossibility to have adequate primary medical care, to the low detection rate of CI, to the prescription of drugs without appropriate indications, and to the denial of psychological correction methods. The review highlights the challenges facing the management of patients with AD and the possible ways of their solution.

Genotypic and Phenotypic Aspects of Longevity: Results from a Sicilian Survey and Implication for the Prevention and Treatment of Age-related Diseases.

It is well known that long living individuals are a model of successful ageing and that the identification of both genetic variants and environmental factors that predispose to a long and healthy life is of tremendous interest for translational medicine. We present the preliminary findings obtained from an ongoing study on longevity conducted on a sample of Sicilian long-lived individuals. We review the characteristics of longevity in Sicily, taking into account lifestyle, environment, genetics, hematochemical values, body composition and immunophenotype. In addition, we discuss the possible implications of our data for the prevention and/or treatment of age-related diseases. As widely discussed in this review, the explanation of the role of genetics and lifestyle in longevity can provide important information on how to develop drugs and/or behaviours that can slow down or delay ageing. Thus, it will be possible to understand, through a "positive biology" approach, how to prevent and/or reduce elderly frailty and disability.

Senotherapeutics: emerging strategy for healthy aging and age-related disease

Cellular senescence (CS) is one of hallmarks of aging and accumulation of senescent cells (SCs) with age contributes to tissue or organismal aging, as well as the pathophysiologies of diverse age-related diseases (ARDs). Genetic ablation of SCs in tissues lengthened health span and reduced the risk of age-related pathologies in a mouse model, suggesting a direct link between SCs, longevity, and ARDs. Therefore, senotherapeutics, medicines targeting SCs, might be an emerging strategy for the extension of health span, and prevention or treatment of ARDs. Senotherapeutics are classified as senolytics which kills SCs selectively; senomorphics which modulate functions and morphology of SCs to those of young cells, or delays the progression of young cells to SCs in tissues; and immune-system mediators of the clearance of SCs. Some senolytics and senomorphics have been proven to markedly prevent or treat ARDs in animal models. This review will present the current status of the development of senotherapeutics, in relation to aging itself and ARDs. Finally, future directions and opportunities for senotherapeutics use will discussed. This knowledge will provide information that can be used to develop novel senotherapeutics for health span and ARDs.

HIF-1 as a Marker of Age-Related Diseases Associated with Tissue Hypoxia

The data on the role of hypoxia-inducible factor, HIF-1, in the development of immunopathology (infectious, inflammatory, and autoimmune diseases), cancer (of the lung, brain, female reproductive system, urinary bladder, and pancreas), diabetes mellitus, and Alzheimer’s disease are analyzed. The data on the genes involving cell differentiation, apoptosis, and proliferation, the expression of which is regulated by HIF-1, are described. HIF-1 activates the expression of the telomerase gene and increases the replicative lifetime of human lung fibroblasts under hypoxic conditions. HIF-1 may be a molecular marker of cell aging and metabolism, as well as a potential therapeutic target for the treatment of age-related diseases.

Tryptophan-Containing Dual Neuroprotective Peptides: Prolyl Endopeptidase Inhibition and Caenorhabditis elegans Protection from β-Amyloid Peptide Toxicity.

Neuroprotective peptides represent an attractive pharmacological strategy for the prevention or treatment of age-related diseases, for which there are currently few effective therapies. Lactoferrin (LF)-derived peptides (PKHs) and a set of six rationally-designed tryptophan (W)-containing heptapeptides (PACEIs) were characterized as prolyl endopeptidase (PEP) inhibitors, and their effect on β-amyloid peptide (Aβ) toxicity in a Caenorhabditis elegans model of Alzheimer’s disease (AD) was evaluated. Two LF-derived sequences, PKH8 and PKH11, sharing a W at the C-terminal end, and the six PACEI heptapeptides (PACEI48L to PACEI53L) exhibited significant in vitro PEP inhibition. The inhibitory peptides PKH11 and PACEI50L also alleviated Aβ-induced paralysis in the in vivo C. elegans model of AD. Partial or total loss of the inhibitory effect on PEP was achieved by the substitution of W residues in PKH11 and PACEI50L and correlated with the loss of protection against Aβ toxicity, pointing out the relevance of W on the neuroprotective activity. Further experiments suggest that C. elegans protection might not be mediated by an antioxidant mechanism but rather by inhibition of Aβ oligomerization and thus, amyloid deposition. In conclusion, novel natural and rationally-designed W-containing peptides are suitable starting leads to design effective neuroprotective agents.

Coumarins as Promising Scaffold for the Treatment of Age-related Diseases - An Overview of the Last Five Years.

Degenerative diseases are becoming more common with increasing life expectancy of the human population. The 20th century faced a progressive demographic change in the industrialized world, followed by identical trends in population aging in Asia, Africa, and Middle and South America. A significant increase in chronic age-dependent disorders will soon cause important challenges for several countries. Age-related pathologies are commonly seen in elderly patients. More than 40% of adults over 60 years old present a combination of risk factors, described as metabolic syndrome, which significantly increases the tendency for developing degenerative diseases, and some types of cancers. Among these, Parkinson's, Alzheimer's and cardiovascular diseases are on the top of the list. The discovery of effective cardio- and neuroprotective alternative therapeutics that decrease or block disease's progression at early stages, is the main goal of research groups working in the field. A wide range of different substituted coumarins, and the pharmacological properties they may display, are trend topics because of their synthetic accessibility, as well as their abundance in plants and other naturally-occurring products. These heterocyclic compounds play an important role in a variety of areas, but stand out in the field of Medicinal Chemistry. This review provides an overview of the last five years about the potential of coumarins as modulators of several physiological mechanisms involved in age-related pathologies.

The Role of Saikosaponins in Therapeutic Strategies for Age-Related Diseases.

As life expectancy increases, elderly populations tend to spend an increasing number of years in poor health, with chronic age-related diseases and disability. Therefore, the development of therapeutic strategies to treat or prevent multiple pathophysiological conditions in the elderly may improve health-adjusted life expectancy and alleviate the potential economic and social burdens arising from age-related diseases. Bioactive natural products might represent promising new drug candidates for the treatment of many chronic age-related diseases, including cancer, Alzheimer's disease, cardiovascular disease, obesity, and liver disease. Here, we discuss a therapeutic option using saikosaponins, which are triterpene saponins isolated from Bupleurum, against a variety of age-related diseases. Understanding the underlying mechanisms of natural products like saikosaponins in the treatment of age-related diseases may help in the development of diverse natural product-derived compounds that may be effective against a number of chronic health problems.

A New Anti-Aging Lysophosphatidic Acid from Arabidopsis thaliana.

Aging is a risk factor of age-related diseases. With the increasing number of patients, serious consequences, and heavy economic burden, demands for drugs used to treat agerelated diseases have increased. As such, anti-aging substances should be isolated to develop drugs for the prevention and treatment of age-related diseases. In this study, a methanol extract of immature Arabidopsis thaliana seeds with coat was separated by using a K6001 yeast bioassay system. In order to investigate the action mechanism, four mutants, namely, Δuth1, Δskn7, Δsod1, and Δsod2 with K6001 background were employed and the anti-oxidative stress assay was performed. One new anti-aging lysophosphatidic acid (LPA) was obtained, and its structural and stereochemical characteristics were elucidated through spectroscopy and chemical derivatization. LPA can extend the replicative lifespan of K6001 at 10 and 30 µM (p < 0.001 and p < 0.01, respectively). This finding was comparable to the effect of resveratrol, a well-known anti-aging substance. However, the anti-aging activity of the compound on the four mutants was diminished. In the antioxidative stress assay, LPA improved the oxidative resistance of yeast cells. The new LPA may exert its anti-aging effect by improving the anti-oxidative ability of yeast cells. The genes of UTH1, SKN7, and SOD may also be involved in the action.