Displaying publications 1 - 20 of 36 in total

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  1. Fulltext Exploring the Causal Relationship Between Telomere Biology and Alzheimer's Disease
    Kuan XY, Fauzi NSA, Ng KY, Bakhtiar A
    Mol Neurobiol, 2023 Aug;60(8):4169-4183.
    PMID: 37046137 DOI: 10.1007/s12035-023-03337-4
    Telomeres, also known as the "protective caps" of our chromosomes, shorten with each cell cycle due to the end replication problem. This process, termed telomere attrition, is associated with many age-related disorders, such as Alzheimer's disease (AD). Despite the numerous studies conducted in this field, the role of telomere attrition in the onset of the disease remains unclear. To investigate the causal relationship between short telomeres and AD, this review aims to highlight the primary factors that regulate telomere length and maintain its integrity, with an additional outlook on the role of oxidative stress, which is commonly associated with aging and molecular damage. Although some findings thus far might be contradictory, telomere attrition likely plays a crucial role in the progression of AD due to its close association with oxidative stress. The currently available treatments for AD are only symptomatic without affecting the progression of the disease. The components of telomere biology discussed in this paper have previously been studied as an alternative treatment option for several diseases and have exhibited promising in vitro and in vivo results. Hence, this should provide a basis for future research to develop a potential therapeutic strategy for AD. (Created with BioRender.com).
    Matched MeSH terms: Aging/genetics
  2. Senotherapeutics for mesenchymal stem cell senescence and rejuvenation
    Wong PF, Dharmani M, Ramasamy TS
    Drug Discov Today, 2023 Jan;28(1):103424.
    PMID: 36332835 DOI: 10.1016/j.drudis.2022.103424
    Mesenchymal stem cells (MSCs) are susceptible to replicative senescence and senescence-associated functional decline, which hampers their use in regenerative medicine. Senotherapeutics are drugs that target cellular senescence through senolytic and senomorphic functions to induce apoptosis and suppress chronic inflammation caused by the senescence-associated secreted phenotype (SASP), respectively. Therefore, senotherapeutics could delay aging-associated degeneration. They could also be used to eliminate senescent MSCs during in vitro expansion or bioprocessing for transplantation. In this review, we discuss the role of senotherapeutics in MSC senescence, rejuvenation, and transplantation, with examples of some tested compounds in vitro. The prospects, challenges, and the way forward in clinical applications of senotherapeutics in cell-based therapeutics are also discussed.
    Matched MeSH terms: Cell Aging/genetics
  3. Fulltext APOE, TOMM40, and sex interactions on neural network connectivity
    Li T, Pappas C, Le ST, Wang Q, Klinedinst BS, Larsen BA, et al.
    Neurobiol Aging, 2022 Jan;109:158-165.
    PMID: 34740077 DOI: 10.1016/j.neurobiolaging.2021.09.020
    The Apolipoprotein E ε4 (APOE ε4) haplotype is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The Translocase of Outer Mitochondrial Membrane-40 (TOMM40) gene maintains cellular bioenergetics, which is disrupted in AD. TOMM40 rs2075650 ('650) G versus A carriage is consistently related to neural and cognitive outcomes, but it is unclear if and how it interacts with APOE. We examined 21 orthogonal neural networks among 8,222 middle-aged to aged participants in the UK Biobank cohort. ANOVA and multiple linear regression tested main effects and interactions with APOE and TOMM40 '650 genotypes, and if age and sex acted as moderators. APOE ε4 was associated with less strength in multiple networks, while '650 G versus A carriage was related to more language comprehension network strength. In APOE ε4 carriers, '650 G-carriage led to less network strength with increasing age, while in non-G-carriers this was only seen in women but not men. TOMM40 may shift what happens to network activity in aging APOE ε4 carriers depending on sex.
    Matched MeSH terms: Aging/genetics
  4. Fulltext An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors
    Nwanaji-Enwerem JC, Chung FF, Van der Laan L, Novoloaca A, Cuenin C, Johansson H, et al.
    Clin Epigenetics, 2021 12 17;13(1):224.
    PMID: 34920739 DOI: 10.1186/s13148-021-01218-y
    Metformin and weight loss relationships with epigenetic age measures-biological aging biomarkers-remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors (N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6 months. Epigenetic age was correlated with chronological age (r = 0.20-0.86; P 
    Matched MeSH terms: Aging/genetics*
  5. Targeting the genetic landscape of oral potentially malignant disorders has the potential as a preventative strategy in oral cancer
    Prime SS, Cirillo N, Cheong SC, Prime MS, Parkinson EK
    Cancer Lett, 2021 10 10;518:102-114.
    PMID: 34139286 DOI: 10.1016/j.canlet.2021.05.025
    This study reviews the molecular landscape of oral potentially malignant disorders (OPMD). We examine the impact of tumour heterogeneity, the spectrum of driver mutations (TP53, CDKN2A, TERT, NOTCH1, AJUBA, PIK3CA, CASP8) and gene transcription on tumour progression. We comment on how some of these mutations impact cellular senescence, field cancerization and cancer stem cells. We propose that OPMD can be monitored more closely and more dynamically through the use of liquid biopsies using an appropriate biomarker of transformation. We describe new gene interactions through the use of a systems biology approach and we highlight some of the first studies to identify functional genes using CRISPR-Cas9 technology. We believe that this information has translational implications for the use of re-purposed existing drugs and/or new drug development. Further, we argue that the use of digital technology encompassing clinical and laboratory-based data will create relevant datasets for machine learning/artificial intelligence. We believe that therapeutic intervention at an early molecular premalignant stage should be an important preventative strategy to inhibit the development of oral squamous cell carcinoma and that this approach is applicable to other aerodigestive tract cancers.
    Matched MeSH terms: Cell Aging/genetics
  6. Fulltext Gene Expression Profile in Different Age Groups and Its Association with Cognitive Function in Healthy Malay Adults in Malaysia
    Abdul Sani NF, Amir Hamzah AIZ, Abu Bakar ZH, Mohd Yusof YA, Makpol S, Wan Ngah WZ, et al.
    Cells, 2021 06 27;10(7).
    PMID: 34199148 DOI: 10.3390/cells10071611
    The mechanism of cognitive aging at the molecular level is complex and not well understood. Growing evidence suggests that cognitive differences might also be caused by ethnicity. Thus, this study aims to determine the gene expression changes associated with age-related cognitive decline among Malay adults in Malaysia. A cross-sectional study was conducted on 160 healthy Malay subjects, aged between 28 and 79, and recruited around Selangor and Klang Valley, Malaysia. Gene expression analysis was performed using a HumanHT-12v4.0 Expression BeadChip microarray kit. The top 20 differentially expressed genes at p < 0.05 and fold change (FC) = 1.2 showed that PAFAH1B3, HIST1H1E, KCNA3, TM7SF2, RGS1, and TGFBRAP1 were regulated with increased age. The gene set analysis suggests that the Malay adult's susceptibility to developing age-related cognitive decline might be due to the changes in gene expression patterns associated with inflammation, signal transduction, and metabolic pathway in the genetic network. It may, perhaps, have important implications for finding a biomarker for cognitive decline and offer molecular targets to achieve successful aging, mainly in the Malay population in Malaysia.
    Matched MeSH terms: Aging/genetics*
  7. Fulltext Potential of Mesenchymal Stem Cells in the Rejuvenation of the Aging Immune System
    Yeo GEC, Ng MH, Nordin FB, Law JX
    Int J Mol Sci, 2021 May 27;22(11).
    PMID: 34072224 DOI: 10.3390/ijms22115749
    Rapid growth of the geriatric population has been made possible with advancements in pharmaceutical and health sciences. Hence, age-associated diseases are becoming more common. Aging encompasses deterioration of the immune system, known as immunosenescence. Dysregulation of the immune cell production, differentiation, and functioning lead to a chronic subclinical inflammatory state termed inflammaging. The hallmarks of the aging immune system are decreased naïve cells, increased memory cells, and increased serum levels of pro-inflammatory cytokines. Mesenchymal stem cell (MSC) transplantation is a promising solution to halt immunosenescence as the cells have excellent immunomodulatory functions and low immunogenicity. This review compiles the present knowledge of the causes and changes of the aging immune system and the potential of MSC transplantation as a regenerative therapy for immunosenescence.
    Matched MeSH terms: Aging/genetics
  8. Fulltext Is There an Interconnection between Epithelial-Mesenchymal Transition (EMT) and Telomere Shortening in Aging?
    Imran SAM, Yazid MD, Idrus RBH, Maarof M, Nordin A, Razali RA, et al.
    Int J Mol Sci, 2021 Apr 09;22(8).
    PMID: 33918710 DOI: 10.3390/ijms22083888
    Epithelial-Mesenchymal Transition (EMT) was first discovered during the transition of cells from the primitive streak during embryogenesis in chicks. It was later discovered that EMT holds greater potential in areas other than the early development of cells and tissues since it also plays a vital role in wound healing and cancer development. EMT can be classified into three types based on physiological functions. EMT type 3, which involves neoplastic development and metastasis, has been the most thoroughly explored. As EMT is often found in cancer stem cells, most research has focused on its association with other factors involving cancer progression, including telomeres. However, as telomeres are also mainly involved in aging, any possible interaction between the two would be worth noting, especially as telomere dysfunction also contributes to cancer and other age-related diseases. Ascertaining the balance between degeneration and cancer development is crucial in cell biology, in which telomeres function as a key regulator between the two extremes. The essential roles that EMT and telomere protection have in aging reveal a potential mutual interaction that has not yet been explored, and which could be used in disease therapy. In this review, the known functions of EMT and telomeres in aging are discussed and their potential interaction in age-related diseases is highlighted.
    Matched MeSH terms: Aging/genetics*
  9. The molecular mechanisms of probiotic strains in improving ageing bone and muscle of d-galactose-induced ageing rats
    Hor YY, Ooi CH, Lew LC, Jaafar MH, Lau AS, Lee BK, et al.
    J Appl Microbiol, 2021 Apr;130(4):1307-1322.
    PMID: 32638482 DOI: 10.1111/jam.14776
    AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system.

    METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P 

    Matched MeSH terms: Aging/genetics
  10. Long live the queen
    Law YH
    Science, 2021 Mar 26;371(6536):1302-1305.
    PMID: 33766870 DOI: 10.1126/science.371.6536.1302
    Matched MeSH terms: Aging/genetics
  11. Fulltext Autophagy is deregulated in cancer-associated fibroblasts from oral cancer and is stimulated during the induction of fibroblast senescence by TGF-β1
    Tan ML, Parkinson EK, Yap LF, Paterson IC
    Sci Rep, 2021 01 12;11(1):584.
    PMID: 33436723 DOI: 10.1038/s41598-020-79789-8
    Many of the characteristics ascribed to cancer-associated fibroblasts (CAFs) are shared by activated, autophagic and senescent fibroblasts. Whilst most oral squamous cell carcinomas (OSCCs) are genetically unstable (GU-OSCC), genetically stable variants (GS-OSCC) have been described and, notably, CAF activation (myofibroblast differentiation) and senescence are characteristics particularly associated with GU-OSCCs. However, it is not known whether autophagy is disrupted in these cells or whether autophagy regulates the development of the myofibroblast and senescent phenotypes. In this study, we show that senescent CAFs from GU-OSCCs contained more autophagosomes than normal human oral fibroblasts (NHOFs) and CAFs from GS-OSCCs possibly due to autophagic impairment. Further, we show that deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-β1, induced fibroblast activation and senescence: In response to TGF-β1, autophagy was induced prior to the development of the activated and senescent phenotypes. Lastly, we show that both SAR405- and TGF-β1-treated NHOFs enhance OSCC cell migration but only TGF-β1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-β1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.
    Matched MeSH terms: Cell Aging/genetics*
  12. Fulltext APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline
    Makkar SR, Lipnicki DM, Crawford JD, Kochan NA, Castro-Costa E, Lima-Costa MF, et al.
    J Gerontol A Biol Sci Med Sci, 2020 09 25;75(10):1863-1873.
    PMID: 32396611 DOI: 10.1093/gerona/glaa116
    We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.
    Matched MeSH terms: Aging/genetics*
  13. Fulltext Over-expression of Nicotinamide phosphoribosyltransferase in mouse cells confers protective effect against oxidative and ER stress-induced premature senescence
    Nuriliani A, Nakahata Y, Ahmed R, Khaidizar FD, Matsui T, Bessho Y
    Genes Cells, 2020 Aug;25(8):593-602.
    PMID: 32533606 DOI: 10.1111/gtc.12794
    A main feature of aged organisms is the accumulation of senescent cells. Accumulated senescent cells, especially stress-induced premature senescent cells, in aged organisms lead to the decline of the regenerative potential and function of tissues. We recently reported that the over-expression of NAMPT, which is the rate-limiting enzyme in mammalian NAD+ salvage pathway, delays replicative senescence in vitro. However, whether Nampt-overexpressing cells are tolerant of stress-induced premature senescence remains unknown. Here, we show that primary mouse embryonic fibroblasts derived from Nampt-overexpressing transgenic mice (Nampt Tg-MEF cells) possess resistance against stress-induced premature senescence in vitro. We found that higher oxidative or endoplasmic reticulum (ER) stress is required to induce premature senescence in Nampt Tg-MEF cells compared to wild-type cells. Moreover, we found that Nampt Tg-MEF cells show acute expression of unfolded protein response (UPR)-related genes, which in turn would have helped to restore proteostasis and avoid cellular senescence. Our results demonstrate that NAMPT/NAD+ axis functions to protect cells not only from replicative senescence, but also from stress-induced premature senescence in vitro. We anticipate that in vivo activation of NAMPT activity or increment of NAD+ would protect tissues from the accumulation of premature senescent cells, thereby maintaining healthy aging.
    Matched MeSH terms: Cell Aging/genetics
  14. Chlorella vulgaris modulates the expression of senescence-associated genes in replicative senescence of human diploid fibroblasts
    Jaafar F, Durani LW, Makpol S
    Mol Biol Rep, 2020 Jan;47(1):369-379.
    PMID: 31642042 DOI: 10.1007/s11033-019-05140-8
    Human diploid fibroblasts (HDFs) cultured in vitro have limited capacity to proliferate after population doubling is repeated several times, and they enter into a state known as replicative senescence or cellular senescence. This study aimed to investigate the effect of Chlorella vulgaris on the replicative senescence of HDFs by determining the expression of senescence-associated genes. Young and senescent HDFs were divided into untreated control and C. vulgaris-treated groups. A senescence-associated gene transcription analysis was carried out with qRT-PCR. Treatment of young HDFs with C. vulgaris reduced the expression of SOD1, CAT and CCS (p 
    Matched MeSH terms: Cell Aging/genetics*
  15. Autophagy and senescence: A new insight in selected human diseases
    Rajendran P, Alzahrani AM, Hanieh HN, Kumar SA, Ben Ammar R, Rengarajan T, et al.
    J Cell Physiol, 2019 12;234(12):21485-21492.
    PMID: 31144309 DOI: 10.1002/jcp.28895
    Senescence and autophagy play important roles in homeostasis. Cellular senescence and autophagy commonly cause several degenerative processes, including oxidative stress, DNA damage, telomere shortening, and oncogenic stress; hence, both events are known to be interrelated. Autophagy is well known for its disruptive effect on human diseases, and it is currently proposed to have a direct effect on triggering senescence and quiescence. However, it is yet to be proven whether autophagy has a positive or negative impact on senescence. It is known that elevated levels of autophagy induce cell death, whereas inadequate autophagy can trigger cellular senescence. Both have important roles in human diseases such as aging, renal degeneration, neurodegenerative disorders, and cancer. Therefore, this review aims to highlight the relevance of senescence and autophagy in selected human ailments through a summary of recent findings on the connection and effects of autophagy and senescence in these diseases.
    Matched MeSH terms: Aging/genetics; Cell Aging/genetics
  16. Does cartilage ERα overexpression correlate with osteoarthritic chondrosenescence? Indications from Labisia pumila OA mitigation
    Madzuki IN, Lau SF, Mohamad Shalan NAA, Mohd Ishak NI, Mohamed S
    J Biosci, 2019 Sep;44(4).
    PMID: 31502578
    Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed after treatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterally ovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX+OA control, OVX+OA + diclofenac (5 mg/kg) (positive control), OVX+OA + LP leaf extract (150 and 300 mg/kg) and healthy sham control. After 8 weeks' treatment, their conditions were evaluated via serum biomarkers, knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilage erosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenac and the non-treated OA. The cartilage catabolic markers' (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa, CASP3 and HIF-2 alpha) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased by LP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilage protective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondral bone restoration. The cartilage ER alpha over-expression showed a strong positive correlation with MMP-13, COL10 alpha1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.
    Matched MeSH terms: Aging/genetics
  17. Fulltext Emerging pathways to neurodegeneration: Dissecting the critical molecular mechanisms in Alzheimer's disease, Parkinson's disease
    Tan SH, Karri V, Tay NWR, Chang KH, Ah HY, Ng PQ, et al.
    Biomed Pharmacother, 2019 Mar;111:765-777.
    PMID: 30612001 DOI: 10.1016/j.biopha.2018.12.101
    Neurodegenerative diseases are usually sporadic in nature and commonly influenced by a wide range of genetic, life style and environmental factors. A unifying feature of Alzheimer's disease (AD) and Parkinson's disease (PD) is the abnormal accumulation and processing of mutant or damaged intra and extracellular proteins; this leads to neuronal vulnerability and dysfunction in the brain. Through a detailed review of ubiquitin proteasome, mRNA splicing, mitochondrial dysfunction, and oxidative stress pathway interrelation on neurodegeneration can improve the understanding of the disease mechanism. The identified pathways common to AD and PD nominate promising new targets for further studies, and as well as biomarkers. These insights suggested would likely provide major stimuli for developing unified treatment approaches to combat neurodegeneration. More broadly, pathways can serve as vehicles for integrating findings from diverse studies of neurodegeneration. The evidence examined in this review provides a brief overview of the current literature on significant pathways in promoting in AD, PD. Additionally, these insights suggest that biomarkers and treatment strategies may require simultaneous targeting of multiple components.
    Matched MeSH terms: Aging/genetics
  18. Fulltext Ventricular pro-arrhythmic phenotype, arrhythmic substrate, ageing and mitochondrial dysfunction in peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β-/-) murine hearts
    Ahmad S, Valli H, Chadda KR, Cranley J, Jeevaratnam K, Huang CL
    Mech Ageing Dev, 2018 Jul;173:92-103.
    PMID: 29763629 DOI: 10.1016/j.mad.2018.05.004
    INTRODUCTION: Ageing and age-related bioenergetic conditions including obesity, diabetes mellitus and heart failure constitute clinical ventricular arrhythmic risk factors.

    MATERIALS AND METHODS: Pro-arrhythmic properties in electrocardiographic and intracellular recordings were compared in young and aged, peroxisome proliferator-activated receptor-γ coactivator-1β knockout (Pgc-1β-/-) and wild type (WT), Langendorff-perfused murine hearts, during regular and programmed stimulation (PES), comparing results by two-way ANOVA.

    RESULTS AND DISCUSSION: Young and aged Pgc-1β-/- showed higher frequencies and durations of arrhythmic episodes through wider PES coupling-interval ranges than WT. Both young and old, regularly-paced, Pgc-1β-/- hearts showed slowed maximum action potential (AP) upstrokes, (dV/dt)max (∼157 vs. 120-130 V s-1), prolonged AP latencies (by ∼20%) and shortened refractory periods (∼58 vs. 51 ms) but similar AP durations (∼50 ms at 90% recovery) compared to WT. However, Pgc-1β-/- genotype and age each influenced extrasystolic AP latencies during PES. Young and aged WT ventricles displayed distinct, but Pgc-1β-/- ventricles displayed similar dependences of AP latency upon (dV/dt)max resembling aged WT. They also independently increased myocardial fibrosis. AP wavelengths combining activation and recovery terms paralleled contrasting arrhythmic incidences in Pgc-1β-/- and WT hearts. Mitochondrial dysfunction thus causes pro-arrhythmic Pgc-1β-/- phenotypes by altering AP conduction through reducing (dV/dt)max and causing age-dependent fibrotic change.

    Matched MeSH terms: Aging/genetics
  19. Role of Sirtuin1-p53 regulatory axis in aging, cancer and cellular reprogramming
    Ong ALC, Ramasamy TS
    Ageing Res Rev, 2018 May;43:64-80.
    PMID: 29476819 DOI: 10.1016/j.arr.2018.02.004
    Regulatory role of Sirtuin 1 (SIRT1), one of the most extensively studied members of its kind in histone deacetylase family in governing multiple cellular fates, is predominantly linked to p53 activity. SIRT1 deacetylates p53 in a NAD+-dependent manner to inhibit transcription activity of p53, in turn modulate pathways that are implicated in regulation of tissue homoeostasis and many disease states. In this review, we discuss the role of SIRT1-p53 pathway and its regulatory axis in the cellular events which are implicated in cellular aging, cancer and reprogramming. It is noteworthy that these cellular events share few common regulatory pathways, including SIRT1-p53-LDHA-Myc, miR-34a,-Let7 regulatory network, which forms a positive feedback loop that controls cell cycle, metabolism, proliferation, differentiation, epigenetics and many others. In the context of aging, SIRT1 expression is reduced as a protective mechanism against oncogenesis and for maintenance of tissue homeostasis. Interestingly, its activation in aged cells is evidenced in response to DNA damage to protect the cells from p53-dependent apoptosis or senescence, predispose these cells to neoplastic transformation. Importantly, the dual roles of SIRT1-p53 axis in aging and tumourigenesis, either as tumour suppressor or tumour promoter are determined by SIRT1 localisation and type of cells. Conceptualising the distinct similarity between tumorigenesis and cellular reprogramming, this review provides a perspective discussion on involvement of SIRT1 in improving efficiency in the induction and maintenance of pluripotent state. Further research in understanding the role of SIRT1-p53 pathway and their associated regulators and strategies to manipulate this regulatory axis very likely foster the development of therapeutics and strategies for treating cancer and aging-associated degenerative diseases.
    Matched MeSH terms: Aging/genetics
  20. Emerging Roles of Sirtuin 6 in Alzheimer's Disease
    Mohamad Nasir NF, Zainuddin A, Shamsuddin S
    J Mol Neurosci, 2018 Feb;64(2):157-161.
    PMID: 29260452 DOI: 10.1007/s12031-017-1005-y
    Alzheimer's disease (AD) is a neurodegenerative disease that is imposing an increasing burden on society. Currently, AD is the leading cause of senile dementia worldwide. Despite the long existence of AD, there is lack of therapies for AD, suggesting that new and effective treatment strategy must be explored. At present, sirtuin pathway has attracted attention from the researchers due to its promising results in laboratory models of aging. In addition, our understanding in the roles of sirtuin 6 in AD has expanded. It has been identified to be involved in telomere maintenance, DNA repair, genome integrity, energy metabolism, and inflammation, which ultimately regulate life span. Recent findings also demonstrate that sirtuin 6 is lacking in AD patients, proposing that it can be a new potential therapeutic target in AD. Therefore, exploring on how sirtuin 6 is related in AD manifestation may accelerate the research of AD further and benefits future AD patients. Keeping that in mind, this review aims to highlight the possible roles of sirtuin 6 in AD manifestation.
    Matched MeSH terms: Aging/genetics
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