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  1. Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH
    Exp Gerontol, 2012 Jun;47(6):458-64.
    PMID: 22759409 DOI: 10.1016/j.exger.2012.03.018
    In recent years, the use of bone marrow mesenchymal stem cell (BMSC) implantation has provided an alternative treatment for osteoarthritis. The objective of this study is to determine whether or not an intra-articular injection of a single dose of autologous chondrogenic induced BMSC could retard the progressive destruction of cartilage in a surgically induced osteoarthritis in sheep. Sheep BMSCs were isolated and divided into two groups. One group was cultured in chondrogenic media containing (Ham's F12:DMEM, 1:1) FD+1% FBS+5 ng/ml TGFβ3+50 ng/ml IGF-1 (CM), and the other group was cultured in the basal media, FD+10% FBS (BM). The procedure for surgically induced osteoarthritis was performed on the donor sheep 6 weeks prior to intra-articular injection into the knee joint of a single dose of BMSC from either group, suspended in 5 ml FD at density of 2 million cells/ml. The control groups were injected with basal media, without cells. Six weeks after injection, gross evidence of retardation of cartilage destruction was seen in the osteoarthritic knee joints treated with CM as well as BM. No significant ICRS (International Cartilage Repair Society) scoring was detected between the two groups with cells. However macroscopically, meniscus repair was observed in the knee joint treated with CM. Severe osteoarthritis and meniscal injury was observed in the control group. Interestingly, histologically the CM group demonstrated good cartilage histoarchitecture, thickness and quality, comparable to normal knee joint cartilage. As a conclusion, intra-articular injection of a single dose of BMSC either chondrogenically induced or not, could retard the progression of osteoarthritis (OA) in a sheep model, but the induced cells indicated better results especially in meniscus regeneration.
    Study site: Universiti Kebangsaan Malaysia, Kuala Lumpur
  2. Chew BH, Ghazali SS, Ismail M, Haniff J, Bujang MA
    Exp Gerontol, 2013 May;48(5):485-91.
    PMID: 23454736 DOI: 10.1016/j.exger.2013.02.017
    Providing effective medical care for older patients with type 2 diabetes mellitus (T2D) that may contribute to their active aging has always been challenging. We examined the independent effect of age ≥ 60 years on disease control and its relationship with diabetes-related complications in patients with T2D in Malaysia. This was a cross-sectional study using secondary data from the electronic diabetes registry database Adult Diabetes Control and Management (ADCM). A total of 303 centers participated and contributed a total of 70,889 patients from May 2008 to the end of 2009. Demographic data, details on diabetes, hypertension, dyslipidemia and their treatment modalities, various risk factors and complications were updated annually. Independent associated risk factors were identified using multivariate regression analyses. Fifty-nine percent were female. Malay comprised 61.9%, Chinese 19% and Indian 18%. There were more Chinese, men, longer duration of diabetes and subjects that were leaner or had lower BMI in the older age group. Patients aged ≥ 60 years achieved glycemic and lipid targets but not the desired blood pressure. After adjusting for duration of diabetes, gender, ethnicity, body mass index, disease control and treatment, a significantly higher proportion of patients ≥ 60 years suffered from reported diabetes-related complications. Age ≥ 60 years was an independent risk factor for diabetes-related complications despite good control of cardiovascular risk factors. Our findings caution against the currently recommended control of targets in older T2D patients with more longstanding diseases and complications.
    Study name: Adult Diabetes Control and Management (ADCM) 2009
  3. Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Bellier JP, et al.
    Exp Gerontol, 2018 Oct 01;111:53-64.
    PMID: 29981398 DOI: 10.1016/j.exger.2018.07.002
    Decrease in multiple functions occurs in the brain with aging, all of which can contribute to age-related cognitive and locomotor impairments. Brain atrophy specifically in hippocampus, medial prefrontal cortex (mPFC), and striatum, can contribute to this age-associated decline in function. Our recent metabolomics analysis showed age-related changes in these brain regions. To further understand the aging processes, analysis using a proteomics approach was carried out. This study was conducted to identify proteome profiles in the hippocampus, mPFC, and striatum of 14-, 18-, 23-, and 27-month-old rats. Proteomics analysis using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins in the striatum. Of these proteins, 97 in the hippocampus, 25 in mPFC, and 5 in striatum were differentially expressed with age. The altered proteins were classified into three ontologies (cellular component, molecular function, and biological process) containing 44, 38, and 35 functional groups in the hippocampus, mPFC, and striatum, respectively. Most of these altered proteins participate in oxidative phosphorylation (e.g. cytochrome c oxidase and ATP synthase), glutathione metabolism (e.g. peroxiredoxins), or calcium signaling pathway (e.g. protein S100B and calmodulin). The most prominent changes were observed in the oldest animals. These results suggest that alterations in oxidative phosphorylation, glutathione metabolism, and calcium signaling pathway are involved in cognitive and locomotor impairments in aging.
  4. Hasenan SM, Karsani SA, Jubri Z
    Exp Gerontol, 2018 11;113:1-9.
    PMID: 30248357 DOI: 10.1016/j.exger.2018.09.001
    Aging is characterized by progressive decline in biochemical and physiological functions. According to the free radical theory of aging, aging results from oxidative damage due to the accumulation of excess reactive oxygen species (ROS). Mitochondria are the main source of ROS production and are also the main target for ROS. Therefore, a diet high in antioxidant such as honey is potentially able to protect the body from ROS and oxidative damage. Gelam honey is higher in flavonoid content and phenolic compounds compared to other local honey. This study was conducted to determine the effects of gelam honey on age related protein expression changes in cardiac mitochondrial rat. A total of 24 Sprague-Dawley male rats were divided into two groups: the young group (2 months old), and aged group (19 months old). Each group were then subdivided into two groups: control group (force-fed with distilled water), and treatment group (force-fed with gelam honey, 2.5 g/kg), and were treated for 8 months. Comparative proteomic analysis of mitochondria from cardiac tissue was then performed by high performance mass spectrometry (Q-TOF LCMS/MS) followed by validation of selected proteins by Western blotting. Proteins were identified using Spectrum Mill software and were subjected to stringent statistical analysis. A total of 286 proteins were identified in the young control group (YC) and 241 proteins were identified in the young gelam group (YG). In the aged group, a total of 243 proteins were identified in control group (OC), and 271 proteins in gelam group (OG). Comparative proteome profiling identified 69 proteins with different abundance (p 
  5. Hamezah HS, Durani LW, Ibrahim NF, Yanagisawa D, Kato T, Shiino A, et al.
    Exp Gerontol, 2017 12 01;99:69-79.
    PMID: 28918364 DOI: 10.1016/j.exger.2017.09.008
    Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age.
  6. Ude CC, Shamsul BS, Ng MH, Chen HC, Ohnmar H, Amaramalar SN, et al.
    Exp Gerontol, 2018 04;104:43-51.
    PMID: 29421350 DOI: 10.1016/j.exger.2018.01.020
    BACKGROUND: Hyaline articular cartilage, which protects the bones of diarthrodial joints from forces associated with load bearing, frictions, and impacts has very limited capacities for self-repair. Over the years, the trend of treatments has shifted to regenerations and researchers have been on the quest for a lasting regeneration. We evaluated the treatment of osteoarthritis by chondrogenically induced ADSCs and BMSCs for a long time functional recovery.

    METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of ACL and medial meniscus. Stem cells from sheep were induced to chondrogenic lineage. Test sheep received 5 mls single doses of 2 × 107 autologous PKH26-labelled ADSCs or BMSCs, while controls received basal medium. Functional recovery of the knees was evaluated via electromyography.

    RESULTS: Induced ADSCs had 625, 255, 393, 908, 409, 157 and 1062 folds increases of collagen I, collagen II, aggrecan, SOX9, cartilage oligomeric protein, chondroadherin and fibromodullin compare to uninduced cells, while BMSCs had 702, 657, 321, 276, 337, 233 and 1163 respectively; p = .001. Immunocytochemistry was positive for these chondrogenic markers. 12 months post-treatment, controls scored 4 in most regions using ICRS, while the treated had 8; P = .001. Regenerated cartilages were positive to PKH26 and demonstrated the presence of condensing cartilages on haematoxylin and eosin; and Safranin O. OA degenerations caused significant amplitude shift from right to left hind limb. After treatments, controls persisted with significant decreases; while treated samples regained balance.

    CONCLUSIONS: Both ADSCs and BMSCs had increased chondrogenic gene expressions using TGF-β3 and BMP-6. The treated knees had improved cartilage scores; PKH26 can provide elongated tracking, while EMG results revealed improved joint recoveries. These could be suitable therapies for osteoarthritis.

  7. Leow SS, Luu A, Shrestha S, Hayes KC, Sambanthamurthi R
    Exp Gerontol, 2018 Mar 15;106:198-221.
    PMID: 29550564 DOI: 10.1016/j.exger.2018.03.013
    Palm fruit juice (PFJ) containing oil palm phenolics is obtained as a by-product from oil palm (Elaeis guineensis) fruit milling. It contains shikimic acid, soluble fibre and various phenolic acids including p-hydroxybenzoic acid and three caffeoylshikimic acid isomers. PFJ has also demonstrated beneficial health properties in various biological models. Increasing concentrations of PFJ and different PFJ fractions were used to assess growth dynamics and possible anti-ageing properties in fruit flies (Drosophila melanogaster) genotype w1118. Microarray gene expression analysis was performed on whole fruit fly larvae and their fat bodies, after the larvae were fed a control Standard Brandeis Diet (SBD) with or without PFJ. Transcripts from Affymetrix GeneChips were utilised to identify the possible mechanisms involved, with genes having fold changes > |1.30| and p 
  8. Li Y, Ren J, Li N, Liu J, Tan SC, Low TY, et al.
    Exp Gerontol, 2020 11;141:111110.
    PMID: 33045358 DOI: 10.1016/j.exger.2020.111110
    BACKGROUND: Dehydroepiandrosterone (DHEA) has been aggressively sold as a dietary supplement to boost testosterone levels although the impact of DHEA supplementation on testosterone levels has not been fully established. Therefore, we performed a systematic review and meta-analysis of RCTs to investigate the effect of oral DHEA supplementation on testosterone levels.

    METHODS: A systematic literature search was performed in Scopus, Embase, Web of Science, and PubMed databases up to February 2020 for RCTs that investigated the effect of DHEA supplementation on testosterone levels. The estimated effect of the data was calculated using the weighted mean difference (WMD). Subgroup analysis was performed to identify the source of heterogeneity among studies.

    RESULTS: Overall results from 42 publications (comprising 55 arms) demonstrated that testosterone level was significantly increased after DHEA administration (WMD: 28.02 ng/dl, 95% CI: 21.44-34.60, p = 0.00). Subgroup analyses revealed that DHEA increased testosterone level in all subgroups, but the magnitude of increment was higher in females compared to men (WMD: 30.98 ng/dl vs. 21.36 ng/dl); DHEA dosage of ˃50 mg/d compared to ≤50 mg/d (WMD: 57.96 ng/dl vs. 19.43 ng/dl); intervention duration of ≤12 weeks compared to ˃12 weeks (WMD: 44.64 ng/dl vs. 19 ng/dl); healthy participants compared to postmenopausal women, pregnant women, non-healthy participants and androgen-deficient patients (WMD: 52.17 ng/dl vs. 25.04 ng/dl, 16.44 ng/dl and 16.47 ng/dl); and participants below 60 years old compared to above 60 years old (WMD: 31.42 ng/dl vs. 23.93 ng/dl).

    CONCLUSION: DHEA supplementation is effective for increasing testosterone levels, although the magnitude varies among different subgroups. More study needed on pregnant women and miscarriage.

  9. Kasim NF, Veldhuijzen van Zanten J, Aldred S
    Exp Gerontol, 2020 07 01;135:110925.
    PMID: 32184194 DOI: 10.1016/j.exger.2020.110925
    Frailty affects the quality of life of older age adults by limiting mobility, reducing physiological reserve and reducing independence. The frailty phenotype is typically characterised by exhaustion, loss or lack of physical activity, weight loss and weakness, although more recently there have been proposals to extend the frailty criteria to include physiological characteristics such as inflammation, oxidative stress and vascular function. Exercise has the potential to prevent, delay or even reverse frailty, but not all exercise is perceived as suitable for an older age population. The purpose of this study was to test Tai Chi and Zumba Gold® as exercise interventions in older age adults (65 to 75 years old) to improve characteristics related to the frailty phenotype. Muscle strength and flexibility (functional fitness as a measure of weakness), cardiorespiratory fitness, blood pressure, vascular function (FMD), markers of oxidative stress (total antioxidant capacity, malondialdehyde, 8-isoprostane, protein carbonyl), inflammation (CRP) and aspects of wellbeing related to exhaustion were assessed at baseline (pre-), 6 weeks (mid-) and 12 weeks (post-intervention). Both Tai Chi and Zumba Gold® improved systolic blood pressure, vascular function, and functional fitness following the 12 week intervention to a similar extent. Furthermore Antioxidant capacity was significantly increased (303 ± 15.56 vs. 336 ± 18.82 μm; p = 0.0028) and lipid oxidation significantly reduced (36.41 ± 6.4 vs 13.49 ± 2.5 pg/ml; p = 0.0042) after 12 weeks of Tai Chi compared to baseline. Anxiety, physical and mental fatigue decreased in both groups, with a greater decrease in mental fatigue in the Tai Chi group. Taken together, these changes suggest that Tai Chi has the potential to reduce outcomes related to the extended frailty phenotype in older age adults.
  10. Xie M, Zhong Y, Xue Q, Wu M, Deng X, O Santos H, et al.
    Exp Gerontol, 2020 07 15;136:110949.
    PMID: 32304719 DOI: 10.1016/j.exger.2020.110949
    BACKGROUND AND AIM: Inconsistencies exist with regard to the influence of dehydroepiandrosterone (DHEA) supplementation on insulin-like growth factor 1 (IGF-1) levels. The inconsistencies could be attributed to several factors, such as dosage, gender, and duration of intervention, among others. To address these inconsistencies, we conducted a systematic review and meta-analysis to combine findings from randomized controlled trials (RCTs) on this topic.

    METHODS: Electronic databases (Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar) were searched for relevant literature published up to February 2020.

    RESULTS: Twenty-four qualified trials were included in this meta-analysis. It was found that serum IGF-1 levels were significantly increased in the DHEA group compared to the control (weighted mean differences (WMD): 16.36 ng/ml, 95% CI: 8.99, 23.74; p = .000). Subgroup analysis revealed that a statistically significant increase in serum IGF-1 levels was found only in women (WMD: 23.30 ng/ml, 95% CI: 13.75, 32.87); in participants who supplemented 50 mg/d DHEA (WMD: 15.75 ng/ml, 95% CI: 7.61, 23.89); in participants undergoing DHEA intervention for >12 weeks (WMD: 17.2 ng/ml, 95% CI: 8.02, 26.22); in participants without an underlying comorbidity (WMD: 19.11 ng/ml, 95% CI: 10.69, 27.53); and in participants over the age of 60 years (WMD: 19.79 ng/ml, 95% CI: 9.86, 29.72).

    CONCLUSION: DHEA supplementation may increase serum IGF-I levels especially in women and older subjects. However, further studies are warranted before DHEA can be recommended for clinical use.

  11. Ramlan H, Damanhuri HA
    Exp Gerontol, 2020 01;129:110779.
    PMID: 31705967 DOI: 10.1016/j.exger.2019.110779
    BACKGROUND: Older people are likely to develop anorexia of aging. Rostral C1 (rC1) catecholaminergic neurons in rostral ventrolateral medulla (RVLM) are recently discovered its role in food intake control. It is well established that these neurons regulate cardiovascular function.

    OBJECTIVE: This study aims to determine the effect of age on the function of rostral C1 (rC1) neurons in mediating feeding response.

    METHOD: Male Sprague Dawley rats at 3-months (n = 22) and 24-months (n = 22) old were used and further divided into two subgroups; 1) treatment group with 2-deoxy-d-glucose (2DG) and 2) vehicle group. Feeding hormones such as cholecystokinin (CCK), ghrelin and leptin were analysed using enzyme-linked immunosorbent assay (ELISA). Rat brain was carefully dissected to obtain the brainstem RVLM region. Further analysis was carried out to determine the level of proteins and genes in RVLM that were associated with feeding pathway. Protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK) and neuropeptide Y Y5 receptor (NPY5R) were determined by western blot. Expression of TH, AMPK and NPY genes were determined by real-time PCR.

    RESULTS: This study showed that blood glucose level was elevated in young and old rats following 2DG administration. Plasma CCK-8 concentration was higher in the aged rats at basal and increased with 2DG administration in young rats, but the leptin and ghrelin showed no changes. Old rats showed higher TH and lower AMPK mRNA levels. Glucoprivation decreased AMPK mRNA level in young rats and decreased TH mRNA in old rats. Aged rC1 neurons showed higher NPY5R protein level. Following glucoprivation, rC1 neurons produced distinct molecular changes across age in which, in young rats, AMPK phosphorylation level was increased and in old rats, TH phosphorylation level was increased.

    CONCLUSION: These findings suggest that glucose-counterregulatory responses by rC1 neurons at least, contribute to the ability of young and old rats in coping glucoprivation. Age-induced molecular changes within rC1 neurons may attenuate the glucoprivic responses. This situation may explain the impairment of feeding response in the elderly.

  12. Azman KF, Safdar A, Zakaria R
    Exp Gerontol, 2021 07 15;150:111372.
    PMID: 33905879 DOI: 10.1016/j.exger.2021.111372
    Aging is associated with a variety of morphological and functional changes in the liver. Oxidative stress and inflammation are now widely accepted as the main mechanisms involved in the aging process that may subsequently cause severe injury to mitochondrial DNA which leads to apoptosis. As aging may increase the risks for various liver diseases and plays as an adverse prognostic factor increasing the mortality rate, knowledge regarding the mechanisms of age-related liver susceptibility and the possible therapeutic interventions is imperative. Due to cost and time constraints, a mimetic aging model is generally preferred to naturally aged animals to study the underlying mechanisms of aging liver. The use of D-galactose in aging research is dated back to 1962 and has since been used widely. This review aims to comprehensively summarize the effects of D-galactose-induced aging on the liver and the underlying mechanisms involved. Its potential therapeutic interventions are also discussed. It is hoped that this invaluable information may facilitate researchers in choosing the appropriate aging model and provide a valuable platform for testing potential therapeutic strategies for the prevention and treatment of age-related liver diseases.
  13. Apparoo Y, Phan CW, Kuppusamy UR, Sabaratnam V
    Exp Gerontol, 2022 Dec;170:111982.
    PMID: 36244584 DOI: 10.1016/j.exger.2022.111982
    Healthy ageing is a crucial process that needs to be highlighted as it affects the quality of lifespan. An increase in oxidative stress along with ageing is the major factor related to the age-associated diseases, especially neurodegenerative disorders. An antioxidant-rich diet has been proven to play a significant role in the ageing process. Targeting ageing mechanisms could be a worthwhile approach to improving health standards. Ergothioneine (EGT), a hydrophilic compound with specific transporter known as OCTN1, has been shown to exert anti-ageing properties. In addition to its antioxidant effect, EGT has been reported to have anti-senescence, anti-inflammatory and anti-neurodegenerative properties. This review aims to define the pivotal role of EGT in major signalling pathways in ageing such as insulin/insulin-like growth factor (IGF) signalling (IIS), sirtuin 6 (SIRT6) and mammalian target of rapamycin complex (mTOR) pathways. The review further discusses evidence of EGT on neurodegeneration in its therapeutic context in various model organisms, providing new insights into improving health. In conclusion, an ergothioneine-rich diet may be beneficial in preventing age-related diseases, resulting in a healthy ageing population.
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