Biochemistry

Cell autocloning as a pathway to their real rejuvenation

The article gives a brief description of geroprotection and rejuvenation methods known to date, presenting their main mechanisms and limitations. To overcome the main limitations of the process of rejuvenation, it is possible to use a process called “cell autocloning.” The principle of the propo...
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The article gives a brief description of geroprotection and rejuvenation methods known to date, presenting their main mechanisms and limitations. To overcome the main limitations of the process of rejuvenation, it is possible to use a process called “cell autocloning.” The principle of the proposed method of rejuvenation is as follows: a periodic process of autocloning of the cell nucleus is initiated in the cellular genome with the formation of one unstable daughter copy and its subsequent self-elimination. In this case, the process of cell division stops in the phase of nuclei divergence without subsequent physical separation of the cell itself. This is especially important for postmitotic cells, where the looping of the “unidirectional” line of the ontogenesis program into a “ring” will mean their transition into renewable cells. The prototype for autocloning mechanisms could be the already known ways in which cells adapt to the increasing amount of their damage over time. These are polyploidy and asymmetric cell division, relying on which it is possible to obtain a renewable process of cell nuclei division, when only the original nucleus remains as a result of division. Although this is not a simple task, there are possible pathways to its solution using approaches that can suggest modern knowledge from the field of molecular and cell biology and genetics. The realization of such a goal will require a lot of work, but the expected result justifies it.
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The Challenge of Unlocking the Biological Secrets of Aging

MtDNA deletions and aging

<jats:p>Aging is the major risk factor in most of the leading causes of mortality worldwide, yet its fundamental causes mostly remain unclear. One of the clear hallmarks of aging is mitochondrial dysfunction. Mitochondria are best known for their roles in cellular energy generation, but they are als...
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<jats:p>Aging is the major risk factor in most of the leading causes of mortality worldwide, yet its fundamental causes mostly remain unclear. One of the clear hallmarks of aging is mitochondrial dysfunction. Mitochondria are best known for their roles in cellular energy generation, but they are also critical biosynthetic and signaling organelles. They also undergo multiple changes with organismal age, including increased genetic errors in their independent, circular genome. A key group of studies looking at mice with increased mtDNA mutations showed that premature aging phenotypes correlated with increased deletions but not point mutations. This generated an interest in mitochondrial deletions as a potential fundamental cause of aging. However, subsequent studies in different models have yielded diverse results. This review summarizes the research on mitochondrial deletions in various organisms to understand their possible roles in causing aging while identifying the key complications in quantifying deletions across all models.</jats:p>
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Carbonic anhydrase production by Pseudomonas fragi

IFN-Aging: Coupling Aging With Interferon Response

Chronic inflammation affects many diseases and conditions, including aging. Interferons are a part of the immune defense against viral infections. Paradoxically, various aging tissues and organs from mammalian hosts perpetually accumulate changes brought by interferon pathway activation. Herein, we ...
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Chronic inflammation affects many diseases and conditions, including aging. Interferons are a part of the immune defense against viral infections. Paradoxically, various aging tissues and organs from mammalian hosts perpetually accumulate changes brought by interferon pathway activation. Herein, we connote the mechanisms behind this phenomenon and discuss its implications in age-related pathology.
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Aging Effects on Epicardial Adipose Tissue

Epicardial fat is the visceral fat of the heart. Epicardial fat is a white adipose tissue, but it displays also brown-fat like or beige fat features. Under physiological conditions, epicardial fat has cardioprotective functions such as free fatty acids supply and thermoregulation of the adjacent myo...
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Epicardial fat is the visceral fat of the heart. Epicardial fat is a white adipose tissue, but it displays also brown-fat like or beige fat features. Under physiological conditions, epicardial fat has cardioprotective functions such as free fatty acids supply and thermoregulation of the adjacent myocardium. Epicardial adipose tissue encounters changes in the transition from embryological to childhood and then to adult life. Aging can affect the function and morphology of epicardial fat, more likely in women than in men. The effect of aging on the brown fat properties of the epicardial fat is the most prominent and with the greatest clinical implications. It is promising to know that epicardial fat responds to newer pharmaceutical drugs modulating the adipose tissue and potentially restoring its browning effects. Epicardial fat pro-inflammatory secretome is down-regulated in end-stage coronary artery disease. Chronic ischemia and adverse hemodynamic conditions can also affect the regulatory component of the epicardial fat. Epicardial fat may incur in apoptotic and fibrotic changes that alter its transcriptome and proteasome. In conclusion, aging and advanced stage of chronic diseases are likely to influence and affect epicardial fat genes and function<jats:bold>.</jats:bold> Whether the downregulation of the epicardial fat tissue is due more to aging than advancing stages of coronary artery disease, or more likely to the combination of both, would be object of future investigations.
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Current and Potential Therapies Targeting Inflammation in NASH

Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD). It is characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. Inflammation plays a key role in the progression of NASH and can be provoked by intrahepatic (e.g., lipot...
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Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD). It is characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. Inflammation plays a key role in the progression of NASH and can be provoked by intrahepatic (e.g., lipotoxicity, immune responses, oxidative stress and cell death) and extrahepatic sources (adipose tissue or gut). The identification of triggers of inflammation is central to understanding the mechanisms in NASH development and progression and in designing targeted therapies that can halt or reverse the disease. In this review, we summarize the current and potential therapies targeting inflammation in NASH.
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Inflammatory Signaling and Brown Fat Activity

DHEAS and Human Development: An Evolutionary Perspective

Adipocyte-Endothelium Crosstalk in Obesity

Obesity is characterized by pathological adipose tissue (AT) expansion. While healthy AT expansion enhances systemic insulin sensitivity, unhealthy AT expansion through increased adipocyte size is associated with insulin resistance, fibrosis, hypoxia, and reduced adipose-derived adiponectin secretio...
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Obesity is characterized by pathological adipose tissue (AT) expansion. While healthy AT expansion enhances systemic insulin sensitivity, unhealthy AT expansion through increased adipocyte size is associated with insulin resistance, fibrosis, hypoxia, and reduced adipose-derived adiponectin secretion. The mechanisms causing the unhealthy AT expansion are not fully elucidated; yet, dysregulated crosstalk between cells within the AT is an important contributor. Evidence from animal and human studies suggests a crucial role of the crosstalk between vascular endothelium (the innermost cell type in blood vessels) and adipocytes for metabolic homeostasis. Arterial endothelial cells are directly involved in maintaining normal organ functions through local blood flow regulation. The endothelial-dependent regulation of blood flow in AT is hampered in obesity, which negatively affects the adipocyte. Moreover, endothelial cells secrete extracellular vesicles (EVs) that target adipocytes in vivo. The endothelial EVs secretion is hampered in obesity and may be affected by the adipocyte-derived adipokine adiponectin. Adiponectin targets the vascular endothelium, eliciting organ-protective functions through binding to T-cadherin. The reduced obesity-induced adiponectin binding of T-cadherin reduces endothelial EV secretion. This affects endothelial health and cell-cell communication between AT cells and distant organs, influencing systemic energy homeostasis. This review focuses on the current understanding of endothelial and adipocyte crosstalk. We will discuss how obesity changes the AT environment and how these changes contribute to obesity-associated metabolic disease in humans. Particularly, we will describe and discuss the EV-dependent communication and regulation between adipocytes, adiponectin, and the endothelial cells regulating systemic energy homeostasis in health and metabolic disease in humans.
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