Archives of Health Science Research Article

Aging, and Diabetes Mellitus: Clinicopathological Correlates, Trends and Targets Dr Chrysanthus Chukwuma Sr* Executive Director, CTR Future-Oriented Ltd, Centre for Future-Oriented Studies, Abakaliki, Ebonyi State, Nigeria. *Corresponding Author: Dr Chrysanthus Chukwuma Sr, Executive Director, CTR Future- Oriented Ltd, Centre for Future-Oriented Studies, Abakaliki, Ebonyi State, Nigeria Abstract: Diabetes and aging correlate with identical organ and system perturbations which are enhanced by concomitant molecular processes such as cellular senescence. Age represents a major risk factor for mellitus. It is unclear how senescence contributes to diabetes pathogenesis. Thus, available treatment modalities have not targeted the vital area of the disease. Reversal of untoward features of cellular aging represents a formidable trajectory for novel type 2 diabetes therapies where dissipation of pancreatic beta cells are impaired for insulin secretion. Furthermore, appropriate therapeutic modalities require characterization of defined senescent beta cell populations and the spatiotemporal variations of the expression of senescence genes. Aging is a dynamic public health dilemma in the prevailing demographic transitions in which a vast majority of those from the sixth decade of life increase exponentially in populations. Researchers have attempted to explicate senescence mechanisms via the identification of novel factors which interact with aging and age-related disorders in furtherance of treatment management, quality of life and lifespan regarding diabetes and its complications. An elucidation of the fundamental mechanisms which result in aging and research-oriented focus on healthy aging will mitigate numerous socioeconomic and healthcare encumbrance now and in the future for diabetes mellitus and related conditions. Keywords: apoptosis, quality of life, lifespan, therapeutic regimen, consequences Introduction diabetes, such as growth hormone axis aberration, elevated circulating glucose, and Aging and diabetes culminate in dysfunctional lipid metabolism which similar organ and system derangements induce senescent cell production. which are undergirded by concomitant Suggestively, senescent cells partially molecular mechanisms including cellular constitute a diabetic pathogenic loop, as senescence. Cellular senescence is combined etiologic agent with resultant fundamentally an aging process indicted in impact of metabolic alterations and tissue several aging-associated disorders, and is perturbations.1 Aging constitutes a major markedly causative of tissue impairment. risk factor for diabetes and several chronic Aggregation of senescent cells results and noncommunicable diseases. Diabetes during the aging process, and is observed prevalence, especially type 2 diabetes contextually in diabetes and obesity [1]. correlates with increasing age, especially in Senecent cells are implicated in the high income countries of persons aged 60 pathogenesis of type 2 diabetes via direct years and over. effect on the functionality of pancreatic beta cell, adipose tissue impairment, senscence- Etiopathological Mechanisms associated secretory phenotype (SASP) - Aging is a fundamental process mediated tissue deterioration. Metabolism involving endothelial dysfunction that and signaling alterations observed in affects both diabetic and normal individuals

Archives of Health Science 1 Aging, Cellular Senescence and Diabetes Mellitus: Clinicopathological Correlates, Trends and Targets

[2]. Aging is an intricate phenomenon limited scope. During insulin resistance, associated with a complex variety of diabetes may not emerge because the molecular metamorphoses depicted by endocrine pancreas has compensatory chronic low grade referred to growth. Impediment on replacement or as ''inflammaging''. Type 2 diabetes displays lifespan decrement may present deranging diverse attributes of aging which are impacts for glucose homeostasis [10]. Type detected at an accelerated inception or or 2 diabetes manifests due to deficiency in expansively expressed coupled with proliferative beta cells response to inflammaging. Type 2 diabetes patients compensate for exacerbated demand due to present with elevated mortality rate linked insulin resistance and partly from senescent with an augmented inflammatory score. The cell accumulation, ostensibly during aging, SASP constitutes the major origin of deranged senescent beta-cell accumulation inflammaging in both type 2 diabetes and contributes to dysfunctional glucose aging. Disparate pathogenic mechanisms intolerance and diabetes as well as associated with progression of type 2 decreased assistance to glucose dilemma as diabetes and development of complications senescent beta cells secrete cytokines and have been inextricably linked to SASP and chemokines (SASP) which perturb proximal senescence, specifically, endoplasmic cells. Acute insulin resistance that is elicited reticulum stress and oxidative stress [3]. by the insulin receptor antagonist S961 or elevated fat diet [11] culminated in Senescence constitutes a cellular expression of aging markers. This suggests response depicted by stable growth that insulin resistance accelerates beta-cell abrogation and several phenotypic changes aging, even as transient hyperglycemia which include a pro-inflammatory induces remarkable altered beta-cell secretome. Senescence contributes to phenotype and dysfunction. Aging is normal growth and development, tissue invariably involved in the dissipation of cell homeostasis sustenance, and restriction of homeostasis with restriction of the lifespan tumour progression as well as the of an organism via an enhanced etiological agent of age-linked disorders [4] susceptibility to disorders and impaired and diabetes and its sequelae [5]. Diabetes tissue regeneration. The glucose uptake and aging result in identical organ connected with energy generation for impairment driven by concurrent molecular optimum cell survival must be taken into mechanisms, namely senescence. The cognizance as a major etiology of the aging phenomena of numerous senescent cells in process as related to diabetes. TXNIP diverse tissues corresponds with increase controls cellular senescence via the in age, diabetes and obesity. Senescent cells inhibition of AKT pathways by direct have been invariably indicted in insulin interaction in the presence of glucose- resistance generation [6]. derived metabolic stress [12]. In vitro and Multiple organ system derangement in vivo, TXNIP regulates AKT-mediated has identical characteristics in diabetes as senescence of cells. AKT activation triggers in normal chronological aging but the glucose uptake, inducing cellular frequency depicts at a younger age in senescence by inhibition of transcriptional diabetes [7]. Diabetic subjects are more functionality and deficiency of both susceptible to the acquisition of age- bradykinin B1 and B2 receptors [13]. associated co-morbidities, for instance, The Cell senescence is a profound debility, frailty, Alzheimer's disease, defense mechanism for the suppression of transient cognitive impairment [8], tumour, and critical in embryonic cardiovascular disorder, ocular development, wound healing, aging and derangement, and renal impairment, as age-related disorders. A senescent cell diabetes replicates a pro-aging condition [9]. depicts remarkable morphological Numerous processes or alterations and dynamic metabolism mechanisms are invariably involved in concurrently with SASP [11]. Cellular chronlogical or pathological aging in both senescence is generated by multifarious normal and diabetic persons, as are evident endogenous and exogenous stressors which in this study. Pancreatic beta-cells sustain prompt senescence [14]. Senescence the glucose contents of the body within a constitutes a programmed phenomenon for Archives of Health Science 2 Aging, Cellular Senescence and Diabetes Mellitus: Clinicopathological Correlates, Trends and Targets the facilitation of beta-cell functional precursor cells and adipose tissue stem as maturation. Thus, senescence may be well as elevated type 2 diabetes risk [19]. associated in beta-cell regeneration, insulin Debilitating metabolic attributes as secretion, diabetes development and well as oxidized small and dense low progression. Senescent cells are in a state of density lipoprotein, ox-dmLDL may be cell cycle cessation but are metabolically contributory to the diminished number and dynamic as they secrete inflammatory the dysfunctionalities of circulating factors. This SASP triggers chronic endothelial progenitors, EPC from normal inflammation, oxidative stress and reduced donors cultured in ox-dmLDL precursors nitric oxide bioaccessibility. The intricate resulted in senescent-like growth interplay between the triad of processes termination. This resultant impact was culminate in age- and diabetes-linked inextricably linked with activation of Akt, cardiovascular derangement [15]. p53 aggregation, p21 expression, Researchers have demonstrated dephosphorylation of retinoblastoma that the progressive dissipation of a protein, protein and with diminished protective CSB associated with Cockayne Syndrome influence against oxidative perturbation. that affects considerable figures of Also, dissipation of endogenous p53 Europeans induces proliferating cells into expression due to small intruding RNA non-reversible aging, and constitutes a indicates that this unperturbed pathway is determinant of senescence or cellular aging pertinent for the occurrence of senescence [16]. The unavailability of CSB protein/ in the Akt/p53/p21 signaling pathway factor or its impairment predisposes to activation and rapid senescence inception mitochondrial derangement, and have been detected in EPC from diabetic clinicopathological features of Cockayne patients [20]. The dissipation of Syndrome, such as premature aging, endogenous p53 in diabetic EPC fails to psychometric deficit, progressive result in senescence-growth suppression, neurological deterioration, photosensitivity and necessitates the propensity to produce and mimetic of the untoward changes in tube-like structures in vitro. These events replicative senescence associated with depict the p53 signaling pathway activation physiological aging. CSB dissipation is as a pertinent mechanism contributing to induced by epigenetic reversible and der7anged diabetes neovascularization regulated modifications of gene expression [20]. Notwithstanding the decreased sustaining the DNA in its native state but proliferative potential, senescent cells impedes its expression at the DNA stage flagrantly display increased metabolic [16]. A molecule that reverses the deficits of activity, with an augmented glycolytic state, Cockrayne syndrome cells of patients even at elevated oxygen concentrations, as attenuates the normal cell disposition to in carcinogenic ambients or cells. The senescence. It is suggested that there is a diversion of pyruvate, the ultimate critical association between accelerated glycolytic product from oxidative pathological aging, and the CSB protein phosphorylation culminates in an altered presents as a veritable factor antagonistic to bioenergetic condition due to augmented senescence. Decrement in naive T-cells in oxidative stress driven by dysfunctional conjunction with elevated levels of memory mitochondrial accumulation. The cells are expected consequences of aging on presenting metabolite shift results in the adaptive immune system [17]. elevated AMP/ATP and ADP/ATP ratios, Immunosuppressive cells subjugate and to the subsequent activation of AMPK activities of myeloid and and lymphoid and culminating in p53-mediated growth effector cells. Aging elicits the regulatory arrest [21]. It is suggested that metabolic cell activity of the immuno-suppressive reprogramming is pertinent to drive network as it affects remodelling of the substantial energy for defined immune system as aging transpires [18]. In functionalities connected to senescence certain events, p14Amf a cellular senescence condition, the SASP and immune response promoter is associated with type 2 diabetes modulation in the microambient of the occurence. HMGA2 and p14Amf functions senescent cell tissue. Irrespective of the within the same framework to induce comparative abundance of oxygen in the respectively, senescence, proliferation of vascular milieu, healthy and potent Archives of Health Science 3 Aging, Cellular Senescence and Diabetes Mellitus: Clinicopathological Correlates, Trends and Targets endothelial cells generate most of their ATP diabetes sequelae. Cessation of the loop via anaerobic glucose to lactate conversion between cell senescence and diabetes via during diabetic senescence. Nicotinamide newfangled modalities against DNA adenine dinucleotide, NAD+ is a vital oxidative perturbations constitutes a crucial cofactor in mitochondrial energy generation trajectory to prevent or curb diabetes and numerous enzymatic redox reactions. complications [23]. Age-linked decline in NAD+ is indicted as a Cellular senescence is an important driving force in multifaceted dimensions of feature in the onset, development and age-related disorders, metabolic, diabetic progression of diabetic nephropathy and neurodegenerative diseases as well as inculcating DNA derangement, telomere deficiency in cellular defense mechanisms attrition, mitochondrial perturbation, against oxidative stress [22]. Klotho dissipation, Wnt/beta-canetenin Cell senescence has been implicated signaling activation, incessant and as a fundamental etiological consequence of persistent inflammation, and uremic toxin type 2 diabetes and its sequelae. Cellular accumulation [24]. Diabetic nephropathy is senescence is the restricted capability of an increasingly prevalent and perturbative human cells to undergo division as depicted disorder that is characterized via alterations in morphology and gene morphologically by degenarative alterations expression. A study [5] enunciated the of renal podocytes correlated with variations implications of telomere attrition, oxidative of foot process excoriation, glomerular stress and pertinent factors or variables in basement membrane thickening, endothelial diabetes premature senescence. A plethora cell damage, and broadening of the of human disorders or perturbations have mesangial matrix as well as progressive been associated with the regulations and renal perturbation [25]. In diabetic functions of genes. These are fundamental nephropathy patients, peculiarities of in environmental signal interpretation for accelerated senescence in the glomeruli the modulation of cells in the functional have been detected. Autophagy is output of the genome. The aging mechanism inextricably linked with the senescent depicts the encompassing manifestation of phenotype, and ostensibly regulates both organisms and gene interaction with the apoptosis and senscence with a probable internal and external milieu. Aging pertains functionality in senescence and autophagy due to a plethora of mechanisms which in mediating glomerular damage in diabetic include factors, such as diabetes, immune nephropathy and elucidation of SASP in system dysfunction, oxidative injury, disease progression as in the invariable magnitude of apoptosis, and telomere establishment of podocyte senescence in attrition. Indivuduals presenting with diabetic nephropathy. shorter telomere lengths are vulnerable to Hyperglycemia-induced retinal premature senescence or accelerated oxidative with oxidative stress may induce biological aging, particularly in diabetic vascular cell aging resulting in vascular subjects as well as glucose intolerance and derangement in diabetic subjects; in elevated blood pressure. Untoward social contrast, physiological aging impacts on attributes may contribute to excruciating primary cells of the retinal pigmented prognosis for diabetic patients in premature epithelium [26]. Hyperglycemia-induced senescence or aging [5]. EPCs are circulating retinal vasculature impairment and diabetic immature cells derived from bone marrow retina progression are connected to with mobilization to the peripheral vascular cell senescence emanating from circulation corresponding to varied stimuli elevated oxidative with nitrative stress. with contribution to vascular homeostasis and compensatory angiogenesis. EPCs Diet and Nutrition in the Management of regenerate damaged endothelium, facilitate Aging and Diabetes re-endotheliazation, and impede Aging predisposes persons to atherosclerotic lesion production. EPCs are chronic and excruciatingly and disparaging deranged in diabetic patients; and elevated cerebrovascular disorders in normal and glucose concentrations ostensibly augment diabetic persons [27]. The specific etiology EPC presence and senescence with of the neuronal deterioration of these resultant development and progression of Archives of Health Science 4 Aging, Cellular Senescence and Diabetes Mellitus: Clinicopathological Correlates, Trends and Targets anomalies and normal brain aging defies senescence and aging, it is imperative to logic. There is beneficial effect of nutrition conduct randomized clinical trials of IF on cognitive functions that research needs against PF and isoenergetic continuous to be developed and broadened in pre- energy deprivations in Man [31, 32]. Thus, clinical and clinical settings to stem or IF may reverse the untoward impacts on ameliorate dysfunctionalities in cognitive health, aging and disease in diabetes and aging [28] as applicable to diabetic patients. obesity with prognosis of a long lifespan. It is suggested that due to the action of Diet and nutrition promote the reversal of oxidative injury in aging and age-related diabetes and accelerated aging [33] or diseases, such as diabetes, it is pertinent to premature senescence5 associated with provide oxidized vitamin E metabolites to chronic disorders. adequately monitor participant functional Endogenous and Exogenous Therapy antioxidant content to elucidate the resultant impact of oxidative stress on aging SASP emerges as a driver and [29] , diabetes and other age-related optimistic therapeutic target for impairments. multifarious age-associated states encompassing diabetes, neurodegenerative Recent anthropogenic activities and and carcinogenic disorders. The contemporary lifestyle in affluent societies, development of a ''SASP Atlas'', provide the latitude for Man to indulge in comprehensively presents a proteomic overconsumption of food. Food database of soluble proteins and exosomal overconsumption oftentimes results in cargo SASP factors emerging from metabolic aberrations, as in visceral fat multifarious inducers and cell types [34]. aggregation, adiposity, insulin resistance Every profile comprises numerous unique and diabetes, particularly with deficient proteins including a subset of proteins physical activity [30]. Since Man evolved in augmented in each SASP. The outcome is environments of relatively sparse food likely to elucidate protein features of SASP supply, he has become adapted to function and document potential senescence both physically and cognitively at an biomarkers to evaluate the encumbrance, elevated level when placed in a food- initiating stimulus and tissue of senescent restricted/fasting condition. Intermittent cells in vivo. fasting, IF and periodic fasting, PF have expansive beneficial impacts on numerous Senolysis and a combined Dasatinib disparate health indices, and counteract and Quercetin can selectively eradicate disease mechanisms, with a better senescent cells, but not non-senescent cells, prognosis in age-associated disorders, such via transient debilitating pro-survival as diabetes, cardiovascular disease, networks which shield them from an auto- carcinogenic and neurological apoptotic milieu. It is suggested that consequences of disorders as in stroke, interventions to decrease senescent cell Alzheimer's disease8 and Parkinson's encumbrance prolong healthspan and disease [31]. IF, PF and time-restricted ameliorate age-related disorders [35], such feeding in normal and obese individuals as diabetes. Mitochondria are cell have established efficacy for weight compartments and ubiquitous in eukaryotic dissipation and good prognosis in multiple cells associating in diverse vital synthetic, health indicators, insulin resistance and risk metabolic and signaling processes. The factor decrement. The cellular and mitochondrial unfolded protein response molecular processes of IF for the (mtUPR) emanates from mitochondrial improvement of health and suppression of reversal of the signal to the nucleus, and disease mechanisms incorporate activation sustain mitochondrial protein homeostasis of adaptive cellular stress response as unfolded and misfolded proteins signaling pathways which augment incessantly accumulate [36]. mtUPR mitochondrial disposition, DNA repair and prevents aging-associated functional autophagy [31]. In addition, PF drives stem- incapacitation and treat disorders cell based regeneration and persistent connected with aging. Accumulation of metabolic impacts. In order to establish the mutated SOD1 in mitochondrial intra- efficacy of IF in the improvement of general membrane space results in mtUPR, and health management of leading disorders of culminates in fALS progression. Archives of Health Science 5 Aging, Cellular Senescence and Diabetes Mellitus: Clinicopathological Correlates, Trends and Targets

Eradication of senescent beta cells dissociative affects [40] in diabetes and arrests immune-mediated beta-cell related diseases. derangement and adequately prevents Parkinsonism is a neurodegenerative diabetes development. Beta-cell senescence disorder depicting motor and non-motor is a major component of type 1 diabetes neuron lesions with resistant, incessant and pathogenesis, and senescent beta-cell persistent progression to fulminating annihilation consitutes a newfangled morbidity, socioeconomic and healthcare therapeutic strategy for the disease. This is encumbrance. The pathologic manifestations achievable because senescent beta cells, include dissipation of dopaminergic neurons upregulated pro-survival mediator Bc1-3 in the substantia nigra pars compacta (SNpc) and NOD mice treatment with Bc1-2 in conjunction with aberrant alpha-synuclein inhibitors selectively annihilated these cells (alpha-syn) deposition of cytoplasmic and did not change the abundance of the inclusions known as Lewy bodies located in immune cell type associated with the pigmented, brainstem nuclei, and dystrophic disease [37]. Elimination of senescent cells neurons in striatal and cortical precincts as by drug application or by defined cell Lewy neurites. In diabetic patients, treatment dissipation of cells expressing the marker for Parkinson's disease targets improved p16Ink4a in transgenic mice restored beta- quality of life and dopaminergic pathways in cell functionality. Identical attributes the decrement of associated motor symptoms manifested in cultured human beta cells, and mitigation of the side effects of L-DOPA depicting translational events [38]. pharmacotherapy [41]. There is extant Eukaryotic genomes harbor numerous significant functionality for dopamine D3 in transposable elements which remain the initial development and presentation of partially functional, and transpose in the Parkinsonism in diabetic patients D3R agonist host genome [39]. There is repression of activation enhances dopamine concentration, mobile element activation to obviate reduces alpha-syn accumulation, augments untoward impacts, such as gene mutations secretion of brain-derived neurotrophic or chromosome rearrangements. factors, alleviates neuroinflammation, Regulation of transposable elements ameliorates oxidative stress, enhances involve diverse mechanisms inculcating neurogenesis in the nigrostriatal pathway, silencing pathways based on small non- interacts with D3R to decrease Parkinson coding RNA generation. Silencing results disease-linked motor neurone systems and with transaposable elemental RNA mitigates side effects of levodopa, L-DOPA degradation or DNA sequence targetting by [41]. heterochromatin production and resultant transcriptional suppression. The gradual The optimal glycemic target in elderly dissipation of heterochromatin in diabetic subjects has to be personalized constitutive heterochromatin regions regarding medical history and comorbidities during aging elicits derepression of with predilection for drugs which correlate to transposable elements leading to low risk of hypoglycemia. For type 2 diabetes progressive elevated genomic instability elderly patients, these include metformin as and inflammatory response activation [39]. first-line agent, pioglitazone, dipeptidyl peptidase-4-inhibitors [42] and glucagon-like Diabetes has perspicuously become pepetide-1-receptor agonists. Precautionary an expansive public health enigma in measures to obviate hypoglycemic risk elderly persons with propensity to exhibit necessitates avoidance of insulin ubiquitous geriatric syndromes, such as secretagogue agents, and if employed, debility/frailty, dementia and cognitive preference must be accorded to short-acting aberration, faecal and urinary incontinence, sulfonylureas as gliclazide, or glinides as trauma, and polytherapy which affect rapaglinide [43]. quality of life and interference in diabetic management. Application of the frailty Discussion index in the determination and establishment of deficit accumulation is an Aging constitutes an encompassing appropriate strategy for the identification of characteristic exhibited or manifested by all elderly persons at risk for expansive bioorganisms, tissues and cells. In the vulnerability, trauma, death and other elucidation of the etiology, consequences Archives of Health Science 6 Aging, Cellular Senescence and Diabetes Mellitus: Clinicopathological Correlates, Trends and Targets and treatment of aging and diabetes, it metamorphosis. These instances may becomes pertinent to configure sustainable present a grim condition of premature or modalities to achieve pertinent goals. accelerated aging or senescence [5]. Also, However, the persistent challenges and mitochondrail derangement characterises constraints in research, therapeutic cellular aging. Mitophagy regulates the regimen, etiology and consequences of the mitochondria via the eradication of comorbidity in aging and diabetes is the gap perturbed mitochondria and drives cell in standardized ecological analysis in sustenance. The maintenance of smooth defining the interaction between mortality muscle cells is potentiated by insulin-like and putative risk factors [44, 45]in aging growth factor 1, IGF-1. However, its and diabetes with its concomitant potential impact on cellular aging [50] or complications. Artificial intelligence aging senescence remains unelucidated. IGF-1 biomarkers provide unrestricted was found to diminish cell aging, disrupt presentation of biological processes or DNA telomere dissipation, elevate mechanisms for newfangled modalities to mitochondrial membrane capacity and enact etiologic models via the extraction of capability and cytochrome coxidase critical characteristic and identification of activation as well as mitigation of biologicol targets and processes [46] as mitochondrial DNA injury in aged or necessary in aging/senescence and diabetes derelict cultured aortic smooth muscle cells. as well as in the convergence of inordinate IGF-1 augmented mitophagy in long-term research disciplines. Diabetes in the elderly cells with concomitant diminished is an unprecedented dilemma to society. expressions of cyclin-dependent kinase The accelerated aging of the global inhibitors p16 and p21 and elevated population has constituted immensely to concentrations of Nrf2 and Sirt3, regulatory the diabetics epidemics as the elderly mechanisms of mitophagy and comprise an exemplified encumbrance of mitochondria biogenesis. The limiting factor the diabetes population. The most was that SiRNA inhibited Sirt3 or Nrf2 with burdensome aspect of these presenting consequent obliteration of IGF-1-mobilised challenges in inter alia healthcare, quality of mitophagy upregulation. It was suggested life and health span is that the elderly that the Nrf2/Sirt3 pathway was pertinent component of the diabetes population is for the impact of IGF-1 on mitophagy. A projected to accelerate in population size perspicuous regulator of mitophagy is [47] contemporaneously with other age- PINK1 that obliterates suppressed related diseases. Healthcare professionals mitophagy and inhibited IGF-1-induced and researchers are rigorously putting all anti-aging influences in decrepit smooth measures in place to manage diabetes and muscle cells as characteristic of mitophagy its complications, the clinical characteristics in the impact of IGF-1 in cellular senescence and the economic impact [48] in the aging [50]. It is perspicuous that IGF-1 constrains population. The propensity of progressive cellular senescence or aging through aging or the chronlogical aging process in a Nrf2/Sirt3-dependent mitophagy vast majority of populations with activation. Ostensibly, activating IGF-1 concomitant pandemic of obesity and signaling constitutes a prospective and concomitant metabolic diseases, such as newfangled modality to induce mitophagy type 2 diabetes has been disseminated in and decelerate aging or cellular senescence older age groups. Adipose tissue aberration in diabetes mellitus and its sequelae. significantly impacts on the aging trajectory culminating in systemic metabolic changes, Conclusion as depicted in chronic inflammatory Aging, cellular senescence, diabetes disorders, ectopic lipid accumulation and and numerous age-related disorders insulin resistance which potentiate obesity constitute challenges which feature normal, risk and type 2 diabetes in the aging physiologic, chronological aging and process [49]. Type 2 diabetes and obesity, clinocopathalogical aging, premature exemplified in adipose tissue perturbation, senescence. Persons in excess of the sixth present several similar physiological decade of life are more prpne to the burden features as aging in elevated encumbrance inextricably connected with healthy and of senescent cells and epigenetic pathological aging in diabetes. The main

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Citation: Dr Chrysanthus Chukwuma Sr, (2020), “Aging, Cellular Senescence and Diabetes Mellitus: Clinicopathological Correlates, Trends and Targets”, Arch Health Sci; 4(1): 1-10.

DOI: 10.31829/2641-7456/ahs2020-4(1)-131

Copyright: © 2020 Dr Chrysanthus Chukwuma Sr. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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