Herbal/Natural Compounds Resist Hallmarks of Brain Aging: From Molecular Mechanisms to Therapeutic Strategies

Aging is a complex process of impaired physiological integrity and function, and is associated with increased risk of cardiovascular disease, diabetes, neurodegeneration, and cancer. The cellular environment of the aging brain exhibits perturbed bioenergetics, impaired adaptive neuroplasticity and flexibility, abnormal neuronal network activity, dysregulated neuronal Ca2+ homeostasis, accumulation of oxidatively modified molecules and organelles, and clear signs of inflammation. These changes make the aging brain susceptible to age-related diseases, such as Alzheimer’s and Parkinson’s diseases. In recent years, unprecedented advances have been made in the study of aging, especially the effects of herbal/natural compounds on evolutionarily conserved genetic pathways and biological processes. Here, we provide a comprehensive review of the aging process and age-related diseases, and we discuss the molecular mechanisms underlying the therapeutic properties of herbal/natural compounds against the hallmarks of brain aging.

[1]  M. Herrero,et al.  Protective Effects of Flavonoid Rutin Against Aminochrome Neurotoxicity , 2023, Neurotoxicity Research.

[2]  Lin Li,et al.  Tetrahydroxy stilbene glucoside alters neurogenesis and neuroinflammation to ameliorate radiation-associated cognitive disability via AMPK/Tet2. , 2022, International immunopharmacology.

[3]  Y. Zeng,et al.  Salidroside attenuates neuronal ferroptosis by activating the Nrf2/HO1 signaling pathway in Aβ1-42-induced Alzheimer’s disease mice and glutamate-injured HT22 cells , 2022, Chinese Medicine.

[4]  Ju Liu,et al.  Icariin ameliorates memory deficits through regulating brain insulin signaling and glucose transporters in 3×Tg-AD mice , 2022, Neural regeneration research.

[5]  G. Wang,et al.  Mitigation of honokiol on fluoride-induced mitochondrial oxidative stress, mitochondrial dysfunction, and cognitive deficits through activating AMPK/PGC-1α/Sirt3. , 2022, Journal of hazardous materials.

[6]  Deao Kong,et al.  ATP-sensitive potassium channels: A double-edged sword in neurodegenerative diseases , 2022, Ageing Research Reviews.

[7]  A. Rego,et al.  Mitochondrial function and dynamics in neural stem cells and neurogenesis: Implications for neurodegenerative diseases , 2022, Ageing Research Reviews.

[8]  I. Mittra,et al.  A pro-oxidant combination of resveratrol and copper down-regulates multiple biological hallmarks of ageing and neurodegeneration in mice , 2022, bioRxiv.

[9]  Mounica Soma,et al.  The role of nicotinamide mononucleotide (NMN) in anti-aging, longevity, and its potential for treating chronic conditions , 2022, Molecular Biology Reports.

[10]  V. Bohr,et al.  Neurogenesis in aging and age-related neurodegenerative diseases , 2022, Ageing Research Reviews.

[11]  M. Sahu,et al.  Cellular senescence in the aging brain: A promising target for neurodegenerative diseases , 2022, Mechanisms of Ageing and Development.

[12]  M. Mattson,et al.  Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain , 2022, GeroScience.

[13]  F. Yousefi,et al.  Mammalian target of rapamycin (mTOR) signaling pathway and traumatic brain injury: A novel insight into targeted therapy , 2022, Cell biochemistry and function.

[14]  Ana Rita de Oliveira dos Santos,et al.  Panax ginseng and aging related disorders: A systematic review , 2022, Experimental Gerontology.

[15]  Rui-ming Liu,et al.  Aging, Cellular Senescence, and Alzheimer’s Disease , 2022, International journal of molecular sciences.

[16]  Xiaoxu Zhang,et al.  Cyanidin 3-O-β-Galactoside Alleviated Cognitive Impairment in Mice by Regulating Brain Energy Metabolism During Aging. , 2022, Journal of agricultural and food chemistry.

[17]  Angela C. C. Jochems,et al.  Contribution of white matter hyperintensities to ventricular enlargement in older adults , 2021, NeuroImage: Clinical.

[18]  Gaofeng Qin,et al.  Shen-Zhi-Ling oral liquid ameliorates cerebral glucose metabolism disorder in early AD via insulin signal transduction pathway in vivo and in vitro , 2021, Chinese Medicine.

[19]  Ronghua Zhang,et al.  The Combination of β-Asarone and Icariin Inhibits Amyloid-β and Reverses Cognitive Deficits by Promoting Mitophagy in Models of Alzheimer's Disease , 2021, Oxidative medicine and cellular longevity.

[20]  Yu Qin,et al.  Chrysophanol exerts neuroprotective effects via interfering with endoplasmic reticulum stress apoptotic pathways in cell and animal models of Alzheimer's disease. , 2021, The Journal of pharmacy and pharmacology.

[21]  J. Weickenmeier,et al.  Brain aging mechanisms with mechanical manifestations , 2021, Mechanisms of Ageing and Development.

[22]  Liping Wang,et al.  Ginsenoside Prolongs the Lifespan of C. elegans via Lipid Metabolism and Activating the Stress Response Signaling Pathway , 2021, International journal of molecular sciences.

[23]  Tingjun Hou,et al.  Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model , 2021, Protein & Cell.

[24]  L. Zhai,et al.  Ginsenoside extract from ginseng extends lifespan and health span in Caenorhabditis elegans. , 2021, Food & function.

[25]  Yih-Ru Wu,et al.  Formulated Chinese medicine Shaoyao Gancao Tang reduces NLRP1 and NLRP3 in Alzheimer’s disease cell and mouse models for neuroprotection and cognitive improvement , 2021, Aging.

[26]  Yun-Lian Lin,et al.  Gastrodiae rhizoma attenuates brain aging via promoting neuritogenesis and neurodifferentiation. , 2021, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[27]  Yee Lian Chew,et al.  Cannabidiol regulates CB1‐pSTAT3 signaling for neurite outgrowth, prolongs lifespan, and improves health span in Caenorhabditis elegans of Aβ pathology models , 2021, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  Y. Kim,et al.  Drug-induced Parkinsonism: A strong predictor of idiopathic Parkinson’s disease , 2021, PloS one.

[29]  M. Moon,et al.  Therapeutic effects of non-saponin fraction with rich polysaccharide from Korean red ginseng on aging and Alzheimer's disease. , 2021, Free radical biology & medicine.

[30]  E. Suzuki,et al.  Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila , 2021, iScience.

[31]  Zhiyong Zhou,et al.  Icariin improves brain function decline in aging rats by enhancing neuronal autophagy through the AMPK/mTOR/ULK1 pathway , 2021, Pharmaceutical biology.

[32]  Libin Zhan,et al.  The ZiBuPiYin recipe regulates proteomic alterations in brain mitochondria-associated ER membranes caused by chronic psychological stress exposure: Implications for cognitive decline in Zucker diabetic fatty rats , 2020, Aging.

[33]  M. Bijak,et al.  Flavonoids as a Natural Enhancer of Neuroplasticity—An Overview of the Mechanism of Neurorestorative Action , 2020, Antioxidants.

[34]  H. Choi,et al.  Amitriptyline interferes with autophagy-mediated clearance of protein aggregates via inhibiting autophagosome maturation in neuronal cells , 2020, Cell Death & Disease.

[35]  E. Tsiani,et al.  Rosemary extract increases neuronal cell glucose uptake and activates AMPK. , 2020, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[36]  S. Fox,et al.  Non-Dopaminergic Treatments for Motor Control in Parkinson’s Disease: An Update , 2020, CNS Drugs.

[37]  Changhua Wang,et al.  Icariin Attenuates Amyloid-β (Aβ)-Induced Neuronal Insulin Resistance Through PTEN Downregulation , 2020, Frontiers in Pharmacology.

[38]  N. Bresolin,et al.  The Role of Mitochondria in Neurodegenerative Diseases: the Lesson from Alzheimer’s Disease and Parkinson’s Disease , 2020, Molecular Neurobiology.

[39]  M. Murphy,et al.  Premature synaptic mitochondrial dysfunction in the hippocampus during aging contributes to memory loss , 2020, Redox biology.

[40]  Han Liu,et al.  Astaxanthin attenuates d-galactose-induced brain aging in rats by ameliorating oxidative stress, mitochondrial dysfunction, and regulating metabolic markers. , 2020, Food & function.

[41]  C. Porro,et al.  The Emerging Role of Curcumin in the Modulation of TLR-4 Signaling Pathway: Focus on Neuroprotective and Anti-Rheumatic Properties , 2020, International journal of molecular sciences.

[42]  G. Kweon,et al.  Schisandra Extract and Ascorbic Acid Synergistically Enhance Cognition in Mice through Modulation of Mitochondrial Respiration , 2020, Nutrients.

[43]  H. Ou,et al.  Anti-Apoptotic Effects of Diosgenin in D-Galactose-Induced Aging Brain. , 2020, The American journal of Chinese medicine.

[44]  A. Sikalidis,et al.  The Gut Microbiome and Type 2 Diabetes Mellitus: Discussing A Complex Relationship , 2020, Biomedicines.

[45]  F. X. Guix,et al.  The interplay between aging‐associated loss of protein homeostasis and extracellular vesicles in neurodegeneration , 2020, Journal of neuroscience research.

[46]  C. Yuan,et al.  Saponins of Panax japonicus attenuate neuronal apoptosis through oxidative stress-related pathways and autophagy in natural aging rats. , 2019, Current pharmaceutical biotechnology.

[47]  Jihyeon Janel Lee,et al.  Extension of Drosophila lifespan by Korean red ginseng through a mechanism dependent on dSir2 and insulin/IGF-1 signaling , 2019, Aging.

[48]  T. Kiss,et al.  Fusogenic liposomes effectively deliver resveratrol to the cerebral microcirculation and improve endothelium-dependent neurovascular coupling responses in aged mice , 2019, GeroScience.

[49]  M. Bucciantini,et al.  Allium roseum L. extract inhibits amyloid beta aggregation and toxicity involved in Alzheimer’s disease , 2019, bioRxiv.

[50]  A. Stolzing,et al.  The role of lipid metabolism in aging, lifespan regulation, and age‐related disease , 2019, Aging cell.

[51]  S. Carding,et al.  Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health , 2019, Gut microbes.

[52]  A. Cianciulli,et al.  Curcumin Regulates Anti-Inflammatory Responses by JAK/STAT/SOCS Signaling Pathway in BV-2 Microglial Cells , 2019, Biology.

[53]  D. Krainc,et al.  Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration , 2019, Neurotherapeutics.

[54]  Bei Zhang,et al.  Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner , 2019, Journal of Neuroinflammation.

[55]  C. Porro,et al.  Modulation of Biological Activities in Glioblastoma Mediated by Curcumin , 2019, Nutrition and cancer.

[56]  N. Isaev,et al.  Neurogenesis and brain aging , 2019, Reviews in the neurosciences.

[57]  Doo Sin Jo,et al.  Peroxisomal dysfunction in neurodegenerative diseases , 2019, Archives of Pharmacal Research.

[58]  Yoshimasa Taniguchi,et al.  Theaflavins Improve Memory Impairment and Depression-Like Behavior by Regulating Microglial Activation , 2019, Molecules.

[59]  J. A. Zweig,et al.  Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in β-amyloid overexpressing mice , 2018, Molecular and Cellular Neuroscience.

[60]  M. Alfaqih,et al.  Phenelzine reduces the oxidative damage induced by peroxynitrite in plasma lipids and proteins , 2018, Archives of physiology and biochemistry.

[61]  B. Narasimhan,et al.  Treatment of neurodegenerative disorders through the blood-brain barrier using nanocarriers. , 2018, Nanoscale.

[62]  Kwang-Soo Kim,et al.  Pluripotent stem cell-based therapy for Parkinson’s disease: Current status and future prospects , 2018, Progress in Neurobiology.

[63]  Jerry Yang,et al.  Translational opportunities for amyloid-targeting fluorophores. , 2018, Chemical communications.

[64]  Yu Tian Wang,et al.  Neuroprotective Effects of Ginsenoside Rf on Amyloid-β-Induced Neurotoxicity in vitro and in vivo. , 2018, Journal of Alzheimer's disease : JAD.

[65]  L. Birder,et al.  Age-related endolysosome dysfunction in the rat urothelium , 2018, PloS one.

[66]  Se Jin Park,et al.  Neuroprotective and Cognitive Enhancement Potentials of Baicalin: A Review , 2018, Brain sciences.

[67]  N. Saha,et al.  Mitigating peroxynitrite mediated mitochondrial dysfunction in aged rat brain by mitochondria-targeted antioxidant MitoQ , 2018, Biogerontology.

[68]  G. Fisone,et al.  Inhibition of mTORC1 Signaling Reverts Cognitive and Affective Deficits in a Mouse Model of Parkinson’s Disease , 2018, Front. Neurol..

[69]  F. Zhang,et al.  Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro , 2018, Front. Mol. Neurosci..

[70]  G. Russo,et al.  Anti-inflammatory effects of flavonoids in neurodegenerative disorders. , 2017, European journal of medicinal chemistry.

[71]  Chenxia Sheng,et al.  Icariin Attenuates Synaptic and Cognitive Deficits in an Aβ1–42-Induced Rat Model of Alzheimer's Disease , 2017, BioMed research international.

[72]  Ning Chen,et al.  Resveratrol as a Natural Autophagy Regulator for Prevention and Treatment of Alzheimer’s Disease , 2017, Nutrients.

[73]  Q. Xiao,et al.  Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury , 2017, Brain, Behavior, and Immunity.

[74]  Mohammad Abdollahi,et al.  Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation , 2017, Ageing Research Reviews.

[75]  A. Kanthasamy,et al.  Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson's Disease , 2017, Journal of neurochemistry.

[76]  A. Grimm,et al.  Brain aging and neurodegeneration: from a mitochondrial point of view , 2017, Journal of neurochemistry.

[77]  P. Alladi,et al.  A novel autophagy modulator 6-Bio ameliorates SNCA/α-synuclein toxicity , 2017, Autophagy.

[78]  W. Ko,et al.  Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate , 2017, Synapse.

[79]  R. Stornetta,et al.  C1 neurons mediate a stress-induced anti-inflammatory reflex in mice , 2017, Nature Neuroscience.

[80]  H. McBride,et al.  Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes , 2017, Nature.

[81]  C. Mammucari,et al.  Calcium at the Center of Cell Signaling: Interplay between Endoplasmic Reticulum, Mitochondria, and Lysosomes. , 2016, Trends in biochemical sciences.

[82]  D. Averill-Bates,et al.  Activation of apoptosis signalling pathways by reactive oxygen species. , 2016, Biochimica et biophysica acta.

[83]  Ju-Hee Lee,et al.  Autophagy flux induced by ginsenoside-Rg3 attenuates human prion protein-mediated neurotoxicity and mitochondrial dysfunction , 2016, Oncotarget.

[84]  E. Bézard,et al.  Ambroxol effects in glucocerebrosidase and α‐synuclein transgenic mice , 2016, Annals of neurology.

[85]  A. Whitworth,et al.  Parkinson disease-linked GBA mutation effects reversed by molecular chaperones in human cell and fly models , 2016, Scientific Reports.

[86]  Yi Sun,et al.  Neuroprotective Effects of A Standardized Flavonoid Extract of Safflower Against Neurotoxin-Induced Cellular and Animal Models of Parkinson’s Disease , 2016, Scientific Reports.

[87]  B. Gulyás,et al.  AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects , 2016, Autophagy.

[88]  Federico N. Soria,et al.  Nanoparticles restore lysosomal acidification defects: Implications for Parkinson and other lysosomal-related diseases , 2016, Autophagy.

[89]  Jia-zuan Ni,et al.  Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple‐Transgenic Alzheimer's Disease Mice , 2016, CNS neuroscience & therapeutics.

[90]  Gilberto Fisone,et al.  Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease , 2015, Progress in Neurobiology.

[91]  A. Khodadadi,et al.  Ellagic Acid Protects the Brain Against 6-Hydroxydopamine Induced Neuroinflammation in a Rat Model of Parkinson’s Disease , 2015, Basic and clinical neuroscience.

[92]  Manuel Rodriguez,et al.  Parkinson's disease as a result of aging , 2015, Aging cell.

[93]  Chi-Rei Wu,et al.  Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson's disease: involvement of antioxidative enzymes induction. , 2015, Chemico-biological interactions.

[94]  J. Obeso,et al.  Clinical and pathological features of Parkinson's disease. , 2015, Current topics in behavioral neurosciences.

[95]  H. Hampel,et al.  Lithium as a Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis. , 2015, Journal of Alzheimer's disease : JAD.

[96]  E. González-Burgos,et al.  Potential Neuroprotective Activity of Ginseng in Parkinson’s Disease: A Review , 2015, Journal of Neuroimmune Pharmacology.

[97]  L. Tan,et al.  Temsirolimus attenuates tauopathy in vitro and in vivo by targeting tau hyperphosphorylation and autophagic clearance , 2014, Neuropharmacology.

[98]  D. Lockhart,et al.  A GCase Chaperone Improves Motor Function in a Mouse Model of Synucleinopathy , 2014, Neurotherapeutics.

[99]  R. Peralta,et al.  Effects of Treating Old Rats with an Aqueous Agaricus blazei Extract on Oxidative and Functional Parameters of the Brain Tissue and Brain Mitochondria , 2014, Oxidative medicine and cellular longevity.

[100]  A. Sikalidis,et al.  Resveratrol increases cerebral glycogen synthase kinase phosphorylation as well as protein levels of drebrin and transthyretin in mice: an exploratory study , 2014, International journal of food sciences and nutrition.

[101]  A. Agrawal,et al.  Protective effect of curcuminoids on age-related mitochondrial impairment in female Wistar rat brain , 2014, Biogerontology.

[102]  C. Gomes,et al.  Neurodegeneration, Neurogenesis, and Oxidative Stress , 2013, Oxidative medicine and cellular longevity.

[103]  Manuel Serrano,et al.  The Hallmarks of Aging , 2013, Cell.

[104]  M. Mansouri,et al.  Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. , 2013, Food chemistry.

[105]  W. Le,et al.  Autophagy enhancer carbamazepine alleviates memory deficits and cerebral amyloid-β pathology in a mouse model of Alzheimer's disease. , 2013, Current Alzheimer research.

[106]  G. Du,et al.  Quercetin protects against the Aβ25–35-induced amnesic injury: Involvement of inactivation of RAGE-mediated pathway and conservation of the NVU , 2013, Neuropharmacology.

[107]  G. B. Louis,et al.  The role of inflammation in age-related disease , 2013, Aging.

[108]  G. Sudhandiran,et al.  Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid-induced neurodegeneration through the activation of nuclear factor-erythroid 2-related factor-2 signalling pathway , 2012, Neuroscience.

[109]  Mark P. Mattson,et al.  Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. , 2012, Cell metabolism.

[110]  Nektarios Tavernarakis,et al.  Calcium homeostasis in aging neurons , 2012, Front. Gene..

[111]  A. Eckert.  Mitochondrial effects of Ginkgo biloba extract , 2012, International Psychogeriatrics.

[112]  E. Vitale,et al.  Role of Cytosolic Calcium-Dependent Phospholipase A2 in Alzheimer's Disease Pathogenesis , 2012, Molecular Neurobiology.

[113]  T. Wyss-Coray,et al.  Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. , 2012, Cold Spring Harbor perspectives in medicine.

[114]  A. Di Stefano,et al.  L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatment. , 2011, Current pharmaceutical design.

[115]  Tao Liu,et al.  The relationship between cortical sulcal variability and cognitive performance in the elderly , 2011, NeuroImage.

[116]  Yifan Han,et al.  Protection against 1-methyl-4-phenylpyridinium ion (MPP+)-induced apoptosis by water extract of ginseng (Panax ginseng C.A. Meyer) in SH-SY5Y cells. , 2011, Journal of ethnopharmacology.

[117]  W. Peng,et al.  Increased mitochondrial DNA damage and decreased base excision repair in the auditory cortex of d-galactose-induced aging rats , 2011, Molecular Biology Reports.

[118]  Myung-Koo Lee,et al.  Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson's disease , 2010, Neuroscience Letters.

[119]  C. Tohda,et al.  Icariin improves memory impairment in Alzheimer's disease model mice (5xFAD) and attenuates amyloid β‐induced neurite atrophy , 2010, Phytotherapy research : PTR.

[120]  A. Cuervo,et al.  Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation , 2010, Neurobiology of Disease.

[121]  R. Chang,et al.  Anti-aging herbal medicine—How and why can they be used in aging-associated neurodegenerative diseases? , 2010, Ageing Research Reviews.

[122]  Tao Liu,et al.  The effects of age and sex on cortical sulci in the elderly , 2010, NeuroImage.

[123]  Fred H. Gage,et al.  Mechanisms Underlying Inflammation in Neurodegeneration , 2010, Cell.

[124]  M. Mattson,et al.  Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia , 2010, Journal of neurochemistry.

[125]  J. Simon,et al.  AMP-activated Protein Kinase Signaling Activation by Resveratrol Modulates Amyloid-β Peptide Metabolism* , 2010, The Journal of Biological Chemistry.

[126]  D. Holtzman,et al.  Acute dosing of latrepirdine (Dimebon™), a possible Alzheimer therapeutic, elevates extracellular amyloid-β levels in vitro and in vivo , 2009, Molecular Neurodegeneration.

[127]  J. Obeso,et al.  Dopaminergic transplantation for parkinson's disease: Current status and future prospects , 2009, Annals of neurology.

[128]  A. Gomes,et al.  Novel nitrogen compounds enhance protection and repair of oxidative DNA damage in a neuronal cell model: comparison with quercetin. , 2009, Chemico-biological interactions.

[129]  M. Mattson,et al.  Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice , 2009, Hippocampus.

[130]  M. Beal,et al.  Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer's mouse model , 2009, Neurobiology of Aging.

[131]  H. Vinters,et al.  β-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin , 2009, The Journal of Neuroscience.

[132]  T. Ajith,et al.  Effect of Ganoderma lucidum on the activities of mitochondrial dehydrogenases and complex I and II of electron transport chain in the brain of aged rats , 2009, Experimental Gerontology.

[133]  Rosanna Abbate,et al.  Adherence to Mediterranean diet and health status: meta-analysis , 2008, BMJ : British Medical Journal.

[134]  M. Mattson,et al.  Hormetic Dietary Phytochemicals , 2008, NeuroMolecular Medicine.

[135]  Tao Lu,et al.  The aging brain. , 2008, Annual review of pathology.

[136]  G. Wang,et al.  Tripchlorolide protects against MPTP‐induced neurotoxicity in C57BL/6 mice , 2007, The European journal of neuroscience.

[137]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[138]  Jun Tan,et al.  ADAM10 Activation Is Required for Green Tea (–)-Epigallocatechin-3-gallate-induced α-Secretase Cleavage of Amyloid Precursor Protein* , 2006, Journal of Biological Chemistry.

[139]  P. Landfield,et al.  Early and Simultaneous Emergence of Multiple Hippocampal Biomarkers of Aging Is Mediated by Ca2+-Induced Ca2+ Release , 2006, The Journal of Neuroscience.

[140]  D. M. Robinson,et al.  Memantine: a review of its use in Alzheimer's disease. , 2006, Drugs.

[141]  Ana Maria Cuervo,et al.  Protein degradation and aging , 2005, Experimental Gerontology.

[142]  Suzanne E. Welcome,et al.  Mapping cortical change across the human life span , 2003, Nature Neuroscience.

[143]  A. Verkhratsky,et al.  Changes in Mitochondrial Status Associated with Altered Ca2+ Homeostasis in Aged Cerebellar Granule Neurons in Brain Slices , 2002, The Journal of Neuroscience.

[144]  M. Mattson,et al.  Folic Acid Deficiency and Homocysteine Impair DNA Repair in Hippocampal Neurons and Sensitize Them to Amyloid Toxicity in Experimental Models of Alzheimer's Disease , 2002, The Journal of Neuroscience.

[145]  H. Fu,et al.  [Effect of wuzi yanzong pill and its disassembled prescription on mitochondrial DNA deletion, respiratory chain complexes and ATP synthesis in aged rats]. , 2001, Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine.

[146]  E. Rogakou,et al.  DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139* , 1998, The Journal of Biological Chemistry.