Thymus atlanticus: A Source of Nutrients with Numerous Health Benefits and Important Therapeutic Potential for Age-Related Diseases.

Thymus atlanticus (Lamiaceae) is a plant endemic to the Mediterranean basin that is found in significant quantities in the arid regions of Morocco. Thymus atlanticus is used in traditional medicine to treat infectious and non-infectious diseases. It is also used for the isolation of essential oils and for the seasoning of many dishes in the Mediterranean diet. The major constituents of Thymus atlanticus are saponins, flavonoids, tannins, alkaloids, various simple and hydroxycinnamic phenolic compounds, and terpene compounds. Several of these compounds act on signaling pathways of oxidative stress, inflammation, and blood sugar, which are parameters often dysregulated during aging. Due to its physiochemical characteristics and biological activities, Thymus atlanticus could be used for the prevention and/or treatment of age-related diseases. These different aspects are treated in the present review, and we focused on phytochemistry and major age-related diseases: dyslipidemia, cardiovascular diseases, and type 2 diabetes.

Pharmacological activities and therapeutic potential of galangin, a promising natural flavone, in age-related diseases.

BACKGROUND: The extension of average life expectancy and the aggravation of population aging have become the inevitable trend of human development. In an aging society, various problems related to medical care for the elderly have become increasingly prominent. However, most of the age-related diseases have the characteristics of multiple diseases at the same time, prone to complications, and atypical clinical manifestations, which bring great difficulties to its treatment. Galangin (3,5,7-trihydroxyflavone) is a natural active compound extracted from the root of Alpinia officinarum Hance (Zingiberaceae). Recently, many studies have shown that galangin has potential advantages in the treatment of neurodegenerative diseases and cardiovascular and cerebrovascular diseases, which are common in the elderly. In addition, it also showed that galangin had prospective activities in the treatment of tumor, diabetes, liver injury, asthma and arthritis. PURPOSE: This review aims to systematically summarize and discuss the effects and the underlying mechanism of galangin in the treatment of age-related diseases. METHODS: We searched PubMed, SciFinder, Web of Science and CNKI literature database resources, combined with the keywords "galangin", "neurodegenerative disease", "tumor", "diabetes", "pharmacological activity", "drug combination", "pharmacokinetics", "drug delivery system" and "safety", and comprehensively reviewed the pharmacological activities and mechanism of galangin in treating age-related diseases. RESULTS: According to the previous studies on galangin, the anti-neurodegenerative activity, cardiovascular and cerebrovascular protective activity, anti-tumor activity, anti-diabetes activity, anti-arthritis activity, hepatoprotective activity and antiasthmatic activity of galangin were discussed, and the related mechanisms were classified and summarized in detail. In addition, the drug combination, pharmacokinetics, drug delivery system and safety of galangin were furtherly discussed. CONCLUSIONS: This review will provide reference for galangin in the treatment of age-related diseases. Meanwhile, further experimental research and long-term clinical trials are needed to determine the therapeutic safety and efficacy of galangin.

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.

Significant Interactions between Adipokines and Vitamin D Combined with the Estimated Glomerular Filtration Rate: A Geriatric Case Study.

Vitamin D deficiency is an important issue in the worldwide population, especially in older people. According to the World Health Organization data, in 2030, 1 in 6 people in the world will be 60 years old or older. The main storage site for vitamin D is adipose tissue. Further, 25(OH)D regulates the expression of adipogenic genes and apoptosis of adipocytes and directly influences the secretion of the appetite-regulating hormone-leptin. Thus, we investigated the impact of the serum concentrations of leptin, adiponectin, omentin, ghrelin, visfatin, and biochemical parameters on vitamin D and estimated glomerular filtration rate (eGFR) in geriatric females. Our studies indicate that the leptin, visfatin and ghrelin are linked with vitamin D concentration and the eGFR rate in the geriatric females. (1) Background: Vitamin D deficiency is common in older people, and researchers are looking for a link between vitamin D deficiency and the occurrence of diseases in advanced age. The study aimed to evaluate the association between serum 25(OH)D levels and clinical variables in older females. (2) Methods: We investigated the impact of the serum concentrations of leptin, adiponectin, omentin, ghrelin, visfatin, and biochemical parameters on vitamin D and estimated the glomerular filtration rate (eGFR) in 74 geriatric females. (3) Results: We observed a significantly higher concentration of creatinine and visfatin in the G2 stage (eGFR = 60-89 mL/min./1.73 m2). We performed an additional analysis to exclude the effect of vitamin D supplementation and obtained a significantly higher vitamin D concentration in the G2 stage. We found significantly lower vitamin D concentrations in older people. In addition, in a person with low levels of vitamin D, we observed significantly lower levels of albumin and ghrelin. Older patients (80 to 89 years old) had significantly lower levels of vitamin D, albumin, insulin, HOMA-IR, and ghrelin than younger patients (60 to 69 years old). Spearman's correlations performed to examine the relationship between clinical variables seemed to confirm previous results. According to ROC curve analysis, leptin concentration was the strongest predictor of vitamin D fluctuations (the area under the curve, AUC = 0.685; with 79.5% sensitivity and 51.4% specificity; p = 0.0291). However, visfatin reached the most accurate AUCROC = 0.651 with 84.2% sensitivity and 49.1% specificity for predicting effects on eGFR. (4) Conclusions: The results suggest that serum levels of leptin, visfatin, and ghrelin are linked with vitamin D concentration and the eGFR rate in the population of geriatric females.

Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan.

Disrupted biological function, manifesting through the hallmarks of aging, poses one of the largest threats to healthspan and risk of disease development, such as metabolic disorders, cardiovascular ailments, and neurodegeneration. In recent years, numerous geroprotectors, senolytics, and other nutraceuticals have emerged as potential disruptors of aging and may be viable interventions in the immediate state of human longevity science. In this review, we focus on the decrease in nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds, to restore NAD+ levels present in youth. Furthermore, these geroprotectors may enhance the efficacy of NMN supplementation while concurrently providing their own numerous health benefits. By analyzing the prevention of NAD+ degradation through the inhibition of CD38 or supporting protective downstream agents of SIRT1, we provide a potential framework of the CD38/NAD+/SIRT1 axis through which geroprotectors may enhance the efficacy of NAD+ precursor supplementation and reduce the risk of age-related diseases, thereby potentiating healthspan in humans.

Immunomodulation in age-related disorders and nanotechnology interventions.

Recently, the aging population has increased exponentially around the globe bringing more challenges to improve quality of life in those populations while reducing the economic burden on healthcare systems. Aging is associated with changes in the immune system culminating in detrimental effects such as immune dysfunction, immunosenescence, and chronic inflammation. Age-related decline of immune functions is associated with various pathologies including cardiovascular, autoimmune, neurodegenerative, and infectious diseases to name a few. Conventional treatment addresses the onset of age-related diseases by early detection of risk factors, administration of vaccines as preventive care, immunomodulatory treatment, and other dietary supplements. However, these approaches often come with systemic side-effects, low bioavailability of therapeutic agents, and poor outcomes seen in the elderly. Recent innovations in nanotechnology have led to the development of novel biomaterials/nanomaterials, which explore targeted drug delivery and immunomodulatory interactions in vivo. Current nanotechnology-based immunomodulatory approaches that have the potential to be used as therapeutic interventions for some prominent age-related diseases are discussed here. Finally, we explore challenges and future aspects of nanotechnology in the treatments of age-related disorders to improve quality of life in the elderly. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK.

The imbalance in osteoblast (OB)-dependent bone formation in favor of osteoclast (OC)-dependent bone resorption is the main cause of loss of tissue mineral mass during bone remodeling leading to osteoporosis conditions. Thus, the suppression of OC activity together with the improvement in the OB activity has been proposed as an effective therapy for maintaining bone mass during aging. We tested the new dietary product, KYMASIN UP containing standardized Withania somnifera, Silybum marianum and Trigonella foenum-graecum herbal extracts or the single extracts in in vitro models mimicking osteoclastogenesis (i.e., RAW 264.7 cells treated with RANKL, receptor activator of nuclear factor kappa-Β ligand) and OB differentiation (i.e., C2C12 myoblasts treated with BMP2, bone morphogenetic protein 2). We found that the dietary product reduces RANKL-dependent TRAP (tartrate-resistant acid phosphatase)-positive cells (i.e., OCs) formation and TRAP activity, and down-regulates osteoclastogenic markers by reducing Src (non-receptor tyrosine kinase) and p38 MAPK (mitogen-activated protein kinase) activation. Withania somnifera appears as the main extract responsible for the anti-osteoclastogenic effect of the product. Moreover, KYMASIN UP maintains a physiological release of the soluble decoy receptor for RANKL, OPG (osteoprotegerin), in osteoporotic conditions and increases calcium mineralization in C2C12-derived OBs. Interestingly, KYMASIN UP induces differentiation in human primary OB-like cells derived from osteoporotic subjects. Based on our results, KYMASIN UP or Withania somnifera-based dietary supplements might be suggested to reverse the age-related functional decline of bone tissue by re-balancing the activity of OBs and OCs, thus improving the quality of life in the elderly and reducing social and health-care costs.

Combination of LC-Q-TOF-MS/MS, network pharmacology, and nanoemulsion approaches identifies active compounds of two Artemisia species responsible for tackling early diabetes-related metabolic complications in the liver.

INTRODUCTION: The chronicity of advanced glycation end-products (AGEs) imparts various damages resulting in metabolic dysfunction and diseases involving inflammation and oxidative stress. The use of plant extracts is of high interest in complementary medicine. Yet, extracts are multicomponent mixtures, and difficult to pinpoint their exact mechanism. OBJECTIVES: We hypothesise that network pharmacology and bioinformatics can help experimental findings depict the exact active components and mechanism of action by which they induce their effects. Additionally, the toxicity and variability can be lowered and standardised with proper encapsulation methods. METHODOLOGY: Here, we propose the formulation of phytoniosomes encapsulating two Artemisia species (Artemisia dracunculus and Artemisia absinthium) to mitigate AGEs and their induced cell redox dysregulation in the liver. Extracts from different solvents were identified via liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS/MS). Phytoniosomes were explored for their anti-glycating effect and modulation of AGE-induced damages in THLE-2 liver cells. Network pharmacology tools were used to identify possible targets and signalling pathways implicated. RESULTS: Data demonstrated that A. absinthium phytoniosomes had a significant anti-AGE effect comparable to reference molecules and higher than A. dracunculus. They were able to restore cell dysfunction through the restoration of tumour necrosis alpha (TNF-α), interleukin 6 (IL-6), nitric oxide, and total antioxidant capacity. Phytoniosomes were able to protect cells from apoptosis by decreasing caspase 3 activity. Network pharmacology and bioinformatic analysis confirmed the induction of the effect via Akt-PI3K-MAPK and AGE-RAGE signalling pathways through quercetin and luteolin actions. CONCLUSION: The current report highlights the potential of Artemisia phytoniosomes as strong contenders in AGE-related disease therapy.

Overview of Traditional Mongolian Medical Warm Acupuncture.

Mongolian medical warm acupuncture is a traditional therapy of Mongolian medicine and was developed by people living on the Mongolian Plateau. This kind of traditional oriental medicine has a long history. The main characteristics of Mongolian medical warm acupuncture are the acupoints and the needles used. Its theory is based on the human anatomical structure and the distinct local culture. Mongolian medical warm acupuncture has been practiced for centuries and proved to be very effective in the treatment of age-related diseases, including the musculoskeletal and nervous diseases. This paper aims to briefly introduce the history and scope of Mongolian medical warm acupuncture, with a particular focus on age-related diseases, where Mongolian medical warm acupuncture has shown significant beneficial effects.

Artemisia alleviates AGE-induced liver complications via MAPK and RAGE signaling pathways modulation: a combinatorial study.

Artemisia herba-alba (AHA) is a traditionally used plant to treat various diseases, including diabetes and metabolic dysfunctions. Plant extracts are generally explored empirically without a deeper assessment of their mechanism of action. Here, we describe a combinatorial study of biochemical, molecular, and bioinformatic (metabolite-protein pharmacology network) analyses to elucidate the mechanism of action of AHA and shed light on its multilevel effects in the treatment of diabetes-related advanced glycation end-products (AGE)-induced liver damages. The extract's polyphenols and flavonoids content were measured and then identified via LC-Q-TOF-MS/MS. Active compounds were used to generate a metabolite-target interaction network via Swiss Target Prediction and other databases. The extract was tested for its antiglycation and aggregation properties. Next, THLE-2 liver cells were challenged with AGEs, and the mechanistic markers were measured [TNF-α, IL-6, nitric oxide, total antioxidant capacity, lipid peroxidation (LPO), and caspase 3]. Metabolite and network screening showed the involvement of AHA in diabetes, glycation, liver diseases, aging, and apoptosis. Experimental confirmation showed that AHA inhibited protein modification and AGE formation. Additionally, AHA reduced inflammatory mediators (IL-6, TNFα), oxidative stress markers (NO, LPO), and apoptosis (Caspase 3). On the other hand, cellular total antioxidant capacity was restored to normal levels. The combinatorial study showed that AHA regulates AGE-induced liver damages through MAPK-AKT and AGE-RAGE signaling pathways. This report highlights the combination of experimental and network pharmacology for the exact elucidation of AHA mechanism of action as a multitarget option in the therapy of diabetes and AGEs-related diseases.

Genistein, a tool for geroscience.

Geroprotection is defined as protection from the adverse effects of aging. The need for geroprotection implies changes towards individually tailored interventions that preserve an individual's independence, physical function, and cognition. Genistein, a phytoestrogen obtained from soya, has been reported to have beneficial properties on age-related diseases such as neurodegenerative and cardiovascular diseases or cancer. Indeed, genistein is a multimodal agent: it acts as a cancer protective agent, promoting apoptosis and cell cycle arrest, and inhibiting angiogenesis and metastasis, but it also acts as an antioxidant, anti-inflammatory, and anti-amyloid-ß and autophagy promoter. Altogether, these properties make genistein a possible treatment for the specific aspects of age-related diseases such as hypertension, metabolic diseases, Alzheimer's disease, and osteoporosis.

Saffron (Crocus sativus L.): A Source of Nutrients for Health and for the Treatment of Neuropsychiatric and Age-Related Diseases.

Saffron (Crocus sativus L.) is a medicinal plant, originally cultivated in the East and Middle East, and later in some Mediterranean countries. Saffron is obtained from the stigmas of the plant. Currently, the use of saffron is undergoing a revival. The medicinal virtues of saffron, its culinary use and its high added value have led to the clarification of its phytochemical profile and its biological and therapeutic characteristics. Saffron is rich in carotenoids and terpenes. The major products of saffron are crocins and crocetin (carotenoids) deriving from zeaxanthin, pirocrocin and safranal, which give it its taste and aroma, respectively. Saffron and its major compounds have powerful antioxidant and anti-inflammatory properties in vitro and in vivo. Anti-tumor properties have also been described. The goal of this review is to present the beneficial effects of saffron and its main constituent molecules on neuropsychiatric diseases (depression, anxiety and schizophrenia) as well as on the most frequent age-related diseases (cardiovascular, ocular and neurodegenerative diseases, as well as sarcopenia). Overall, the phytochemical profile of saffron confers many beneficial virtues on human health and, in particular, on the prevention of age-related diseases, which is a major asset reinforcing the interest for this medicinal plant.

Advances in Understanding of the Role of Lipid Metabolism in Aging.

During aging, body adiposity increases with changes in the metabolism of lipids and their metabolite levels. Considering lipid metabolism, excess adiposity with increased lipotoxicity leads to various age-related diseases, including cardiovascular disease, cancer, arthritis, type 2 diabetes, and Alzheimer's disease. However, the multifaceted nature and complexities of lipid metabolism make it difficult to delineate its exact mechanism and role during aging. With advances in genetic engineering techniques, recent studies have demonstrated that changes in lipid metabolism are associated with aging and age-related diseases. Lipid accumulation and impaired fatty acid utilization in organs are associated with pathophysiological phenotypes of aging. Changes in adipokine levels contribute to aging by modulating changes in systemic metabolism and inflammation. Advances in lipidomic techniques have identified changes in lipid profiles that are associated with aging. Although it remains unclear how lipid metabolism is regulated during aging, or how lipid metabolites impact aging, evidence suggests a dynamic role for lipid metabolism and its metabolites as active participants of signaling pathways and regulators of gene expression. This review describes recent advances in our understanding of lipid metabolism in aging, including established findings and recent approaches.

Attenuation of 7-ketocholesterol- and 7ß-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases.

Age-related diseases for which there are no effective treatments include cardiovascular diseases; neurodegenerative diseases such as Alzheimer's disease; eye disorders such as cataract and age-related macular degeneration; and, more recently, Severe Acute Respiratory Syndrome (SARS-CoV-2). These diseases are associated with plasma and/or tissue increases in cholesterol derivatives mainly formed by auto-oxidation: 7-ketocholesterol, also known as 7-oxo-cholesterol, and 7ß-hydroxycholesterol. The formation of these oxysterols can be considered as a consequence of mitochondrial and peroxisomal dysfunction, leading to increased in oxidative stress, which is accentuated with age. 7-ketocholesterol and 7ß-hydroxycholesterol cause a specific form of cytotoxic activity defined as oxiapoptophagy, including oxidative stress and induction of death by apoptosis associated with autophagic criteria. Oxiaptophagy is associated with organelle dysfunction and in particular with mitochondrial and peroxisomal alterations involved in the induction of cell death and in the rupture of redox balance. As the criteria characterizing 7-ketocholesterol- and 7ß-hydroxycholesterol-induced cytotoxicity are often simultaneously observed in major age-related diseases (cardiovascular diseases, age-related macular degeneration, Alzheimer's disease) the involvement of these oxysterols in the pathophysiology of the latter seems increasingly likely. It is therefore important to better understand the signalling pathways associated with the toxicity of 7-ketocholesterol and 7ß-hydroxycholesterol in order to identify pharmacological targets, nutrients and synthetic molecules attenuating or inhibiting the cytotoxic activities of these oxysterols. Numerous natural cytoprotective compounds have been identified: vitamins, fatty acids, polyphenols, terpenes, vegetal pigments, antioxidants, mixtures of compounds (oils, plant extracts) and bacterial enzymes. However, few synthetic molecules are able to prevent 7-ketocholesterol- and/or 7ß-hydroxycholesterol-induced cytotoxicity: dimethyl fumarate, monomethyl fumarate, the tyrosine kinase inhibitor AG126, memantine, simvastatine, Trolox, dimethylsufoxide, mangafodipir and mitochondrial permeability transition pore (MPTP) inhibitors. The effectiveness of these compounds, several of which are already in use in humans, makes it possible to consider using them for the treatment of certain age-related diseases associated with increased plasma and/or tissue levels of 7-ketocholesterol and/or 7ß-hydroxycholesterol.

Coenzyme Q homeostasis in aging: Response to non-genetic interventions.

Coenzyme Q (CoQ) is a key component for many essential metabolic and antioxidant activities in cells in mitochondria and cell membranes. Mitochondrial dysfunction is one of the hallmarks of aging and age-related diseases. Deprivation of CoQ during aging can be the cause or the consequence of this mitochondrial dysfunction. In any case, it seems clear that aging-associated CoQ deprivation accelerates mitochondrial dysfunction in these diseases. Non-genetic prolongevity interventions, including CoQ dietary supplementation, can increase CoQ levels in mitochondria and cell membranes improving mitochondrial activity and delaying cell and tissue deterioration by oxidative damage. In this review, we discuss the importance of CoQ deprivation in aging and age-related diseases and the effect of prolongevity interventions on CoQ levels and synthesis and CoQ-dependent antioxidant activities.

Novel insights into ferroptosis: Implications for age-related diseases.

Rapid increase in aging populations is an urgent problem because older adults are more likely to suffer from disabilities and age-related diseases (ARDs), burdening healthcare systems and society in general. ARDs are characterized by the progressive deterioration of tissues and organs over time, eventually leading to tissue and organ failure. To date, there are no effective interventions to prevent the progression of ARDs. Hence, there is an urgent need for new treatment strategies. Ferroptosis, an iron-dependent cell death, is linked to normal development and homeostasis. Accumulating evidence, however, has highlighted crucial roles for ferroptosis in ARDs, including neurodegenerative and cardiovascular diseases. In this review, we a) summarize initiation, regulatory mechanisms, and molecular signaling pathways involved in ferroptosis, b) discuss the direct and indirect involvement of the activation and/or inhibition of ferroptosis in the pathogenesis of some important diseases, and c) highlight therapeutic targets relevant for ARDs.

Tectochrysin increases stress resistance and extends the lifespan of Caenorhabditis elegans via FOXO/DAF-16.

Aging is related to the lowered overall functioning and increased risk for various age-related diseases in humans. Tectochrysin is a flavonoid compound and rich in a traditional Chinese Medicine Alpinia oxyphylla Miq., which has antioxidant, anti-inflammatory, anti-cancer, anti-bacterial, anti-diarrhea, hepatoprotective, and neuro-protective effects. Therefore, we tested if tectochrysin had an effect on aging in Caenorhabditis elegans (C. elegans). Our results showed that tectochrysin could extend the lifespan of C. elegans by up to 21.0%, delay the age-related decline of body movement, improve high temperature-stress resistance and anti-infection capacity, and protected worms against Aß1-42-induced toxicity. Tectochrysin could not extend the lifespan of the mutants from genes daf-2, daf-16, eat-2, aak-2, skn-1, and hsf-1. Tectochrysin could increase the expression of DAF-16 regulated genes. The extension of lifespan by tectochrysin requires FOXO/DAF-16 and HSF-1. Overall, our findings suggest that tectochrysin may have a potential effect on extending lifespan and age-related diseases.

Plant Polyphenols, More than Just Simple Natural Antioxidants: Oxidative Stress, Aging and Age-Related Diseases.

The present editorial serves as an introduction to the Special Issue "Antioxidant and Anti-aging Action of Plant Polyphenols". It also provides a summary of the polyphenols, their biological properties and possible functions as medicines, the importance of traditional medicines as a source of inspiration, the rationalization of new uses of plant extracts which lead to applications in modern medicine, the status of modern green-chemistry extraction methods, and some reflections on future prospects. Here, the articles from this Special Issue, and the main aspects of the antioxidant and anti-aging effects of plant polyphenols are discussed in the form of seven questions.

Obesity and ageing: Two sides of the same coin.

Conditions and comorbidities of obesity mirror those of ageing and age-related diseases. Obesity and ageing share a similar spectrum of phenotypes such as compromised genomic integrity, impaired mitochondrial function, accumulation of intracellular macromolecules, weakened immunity, shifts in tissue and body composition, and enhanced systemic inflammation. Moreover, it has been shown that obesity reduces life expectancy by 5.8 years in men and 7.1 years in women after the age of 40. Shorter life expectancy could be because obesity holistically accelerates ageing at multiple levels. Besides jeopardizing nuclear DNA and mitochondrial DNA integrity, obesity modifies the DNA methylation pattern, which is associated with epigenetic ageing in different tissues. Additionally, other signs of ageing are seen in individuals with obesity including telomere shortening, systemic inflammation, and functional declines. This review aims to show how obesity and ageing are "two sides of the same coin" through discussing how obesity predisposes an individual to age-related conditions, illness, and disease. We will further demonstrate how the mechanisms that perpetuate the early-onset of chronic diseases in obesity parallel those of ageing.