Novel Insights into the Roles and Mechanisms of GLP-1 Receptor Agonists against Aging-Related Diseases

Wei, Ping; Zhou, Rui; Sun, Zhaoqing; Long, Jia-Wei; Gong, Yan

doi:10.14336/ad.2021.0928

Cited by 26 publications

(8 citation statements)

References 176 publications

(189 reference statements)

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“…Similar cardioprotective roles of GLP-1(9-36) have been observed in dog models with dilated cardiomyopathy [16] and cultured cardiac cells of Goto-Kakizaki rats [17]. It has been suggested that GLP-1(9-36) amide is an active form at physiological concentration, while other GLP-1 metabolites, such as GLP-1 (28)(29)(30)(31)(32)(33)(34)(35)(36) and GLP-1 (32)(33)(34)(35)(36), are metabolically inactive [18]. However, growing evidence suggested that some of these metabolites may contribute to pleiotropic effects of GLP-1, irrespective of the GLP-1R [19,20].…”

Section: Introductionmentioning

confidence: 58%

Multifaceted Roles of GLP-1 and Its Analogs: A Review on Molecular Mechanisms with a Cardiotherapeutic Perspective

2023

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Diabetes is one of the chronic metabolic disorders which poses a multitude of life-debilitating challenges, including cardiac muscle impairment, which eventually results in heart failure. The incretin hormone glucagon-like peptide-1 (GLP-1) has gained distinct recognition in reinstating glucose homeostasis in diabetes, while it is now largely accepted that it has an array of biological effects in the body. Several lines of evidence have revealed that GLP-1 and its analogs possess cardioprotective effects by various mechanisms related to cardiac contractility, myocardial glucose uptake, cardiac oxidative stress and ischemia/reperfusion injury, and mitochondrial homeostasis. Upon binding to GLP-1 receptor (GLP-1R), GLP-1 and its analogs exert their effects via adenylyl cyclase-mediated cAMP elevation and subsequent activation of cAMP-dependent protein kinase(s) which stimulates the insulin release in conjunction with enhanced Ca2+ and ATP levels. Recent findings have suggested additional downstream molecular pathways stirred by long-term exposure of GLP-1 analogs, which pave the way for the development of potential therapeutic molecules with longer lasting beneficial effects against diabetic cardiomyopathies. This review provides a comprehensive overview of the recent advances in the understanding of the GLP-1R-dependent and -independent actions of GLP-1 and its analogs in the protection against cardiomyopathies.

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Section: Introductionmentioning

confidence: 58%

Multifaceted Roles of GLP-1 and Its Analogs: A Review on Molecular Mechanisms with a Cardiotherapeutic Perspective

2023

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“…The underlying mechanisms by which GLP-1 RA and SGLT2i provide this protection are not fully understood. It has been proposed that the beneficial effects of these drugs may be partly mediated by antioxidative actions [164,165]. Thus, GLP1 RA have shown protection against oxidative stress, cellular senescence, and chronic inflammation in aging-related diseases [165].…”

Section: Discussionmentioning

confidence: 99%

“…It has been proposed that the beneficial effects of these drugs may be partly mediated by antioxidative actions [164,165]. Thus, GLP1 RA have shown protection against oxidative stress, cellular senescence, and chronic inflammation in aging-related diseases [165]. Similarly, the administration of SGLT2i ameliorated oxidative stress in experimental models of diabetes, diabetic nephropathy, and septic AKI [164,166].…”

Section: Discussionmentioning

confidence: 99%

Klotho, Oxidative Stress, and Mitochondrial Damage in Kidney Disease

et al. 2023

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Reducing oxidative stress stands at the center of a prevention and control strategy for mitigating cellular senescence and aging. Kidney disease is characterized by a premature aging syndrome, and to find a modulator targeting against oxidative stress, mitochondrial dysfunction, and cellular senescence in kidney cells could be of great significance to prevent and control the progression of this disease. This review focuses on the pathogenic mechanisms related to the appearance of oxidative stress damage and mitochondrial dysfunction in kidney disease. In this scenario, the anti-aging Klotho protein plays a crucial role by modulating signaling pathways involving the manganese-containing superoxide dismutase (Mn-SOD) and the transcription factors FoxO and Nrf2, known antioxidant systems, and other known mitochondrial function regulators, such as mitochondrial uncoupling protein 1 (UCP1), B-cell lymphoma-2 (BCL-2), Wnt/β-catenin, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), transcription factor EB, (TFEB), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Therefore, Klotho is postulated as a very promising new target for future therapeutic strategies against oxidative stress, mitochondria abnormalities, and cellular senescence in kidney disease patients.

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“…Furthermore, it was revealed through MRI that AD and frontal temporal dementia are connected with focal volume loss in the cerebellum. Therefore, although AD's effect on motor function in the cerebellum may be debatable, it seems to contribute to inevitable dementia related to the disease [136,137].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Cerebellum and Aging: Update and Challenges

2024

Aging dis

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The cerebellum plays a vital role in the aging process. With the aging of the cerebellum, there is a decline in balance and motor function, particularly fine motor skills, and an increased risk of falling. However, in recent years, numerous studies have revealed that the cerebellum has several roles beyond balance and fine motor skills, such as cognitive function and memory. It also plays a role in many neurodegenerative diseases. Interestingly, the cerebellum ages more rapidly than other brain regions, including the hippocampus. With increasing studies reporting that the cerebellum has a more prominent and interconnected role in the brain, it is essential to understand why aging affects it more, leading to solutions to help curb the accelerated decline. Here, we summarize the cerebellum's function and look at how it ages at the cellular, molecular, and functional levels. Additionally, we explore the the effects of alcoholism on the aging cerebellum as well as the role of the cerebellum in diseases such as Alzheimer's, Parkinson's, and Multiple Sclerosis.

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Novel Insights into the Roles and Mechanisms of GLP-1 Receptor Agonists against Aging-Related Diseases

Cited by 26 publications

References 176 publications

Multifaceted Roles of GLP-1 and Its Analogs: A Review on Molecular Mechanisms with a Cardiotherapeutic Perspective

Multifaceted Roles of GLP-1 and Its Analogs: A Review on Molecular Mechanisms with a Cardiotherapeutic Perspective

Klotho, Oxidative Stress, and Mitochondrial Damage in Kidney Disease

Cerebellum and Aging: Update and Challenges

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