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      Research progress of AMP-activated protein kinase and cardiac aging

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          Abstract

          The process of aging is marked by a gradual deterioration in the physiological functions and functional reserves of various tissues and organs, leading to an increased susceptibility to diseases and even death. Aging manifests in a tissue- and organ-specific manner, and is characterized by varying rates and direct and indirect interactions among different tissues and organs. Cardiovascular disease (CVD) is the leading cause of death globally, with older adults (aged >70 years) accounting for approximately two-thirds of CVD-related deaths. The prevalence of CVD increases exponentially with an individual’s age. Aging is a critical independent risk factor for the development of CVD. AMP-activated protein kinase (AMPK) activation exerts cardioprotective effects in the heart and restores cellular metabolic functions by modulating gene expression and regulating protein levels through its interaction with multiple target proteins. Additionally, AMPK enhances mitochondrial function and cellular energy status by facilitating the utilization of energy substrates. This review focuses on the role of AMPK in the process of cardiac aging and maintaining normal metabolic levels and redox homeostasis in the heart, particularly in the presence of oxidative stress and the invasion of inflammatory factors.

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          AMPK: guardian of metabolism and mitochondrial homeostasis.

          Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy. This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.
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            Cardiovascular Risks Associated with Gender and Aging

            The aging and elderly population are particularly susceptible to cardiovascular disease. Age is an independent risk factor for cardiovascular disease (CVD) in adults, but these risks are compounded by additional factors, including frailty, obesity, and diabetes. These factors are known to complicate and enhance cardiac risk factors that are associated with the onset of advanced age. Sex is another potential risk factor in aging adults, given that older females are reported to be at a greater risk for CVD than age-matched men. However, in both men and women, the risks associated with CVD increase with age, and these correspond to an overall decline in sex hormones, primarily of estrogen and testosterone. Despite this, hormone replacement therapies are largely shown to not improve outcomes in older patients and may also increase the risks of cardiac events in older adults. This review discusses current findings regarding the impacts of age and gender on heart disease.
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              AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control

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                Author and article information

                Contributors
                Journal
                Open Life Sci
                Open Life Sci
                biol
                Open Life Sciences
                De Gruyter
                2391-5412
                29 August 2023
                2023
                : 18
                : 1
                : 20220710
                Affiliations
                Faculty of Medicine, Macau University of Science and Technology , Taipa, Macao SAR 999078, China
                Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Carson International Cancer Center, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Shenzhen University , Shenzhen 518060, China
                Author notes
                tel: +86-19981665094
                Article
                biol-2022-0710
                10.1515/biol-2022-0710
                10476487
                37671091
                5f9c201a-eb2a-4e61-b8f7-65d87927c219
                © 2023 the author(s), published by De Gruyter

                This work is licensed under the Creative Commons Attribution 4.0 International License.

                History
                : 27 February 2023
                : 27 July 2023
                : 05 August 2023
                Page count
                Pages: 14
                Categories
                Review Article

                amp-activated protein kinase,aging,cardiac senescence,autophagy,reactive oxygen species

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