The KEAP1-NRF2 System in Healthy Aging and Longevity

Aging is inevitable, but the inherently and genetically programmed aging process is markedly influenced by environmental factors. All organisms are constantly exposed to various stresses, either exogenous or endogenous, throughout their lives, and the quality and quantity of the stresses generate diverse impacts on the organismal aging process. In the current oxygenic atmosphere on earth, oxidative stress caused by reactive oxygen species is one of the most common and critical environmental factors for life. The Kelch-like ECH-associated protein 1-NFE2-related factor 2 (KEAP1-NRF2) system is a critical defense mechanism of cells and organisms in response to redox perturbations. In the presence of oxidative and electrophilic insults, the thiol moieties of cysteine in KEAP1 are modified, and consequently NRF2 activates its target genes for detoxification and cytoprotection. A number of studies have clarified the contributions of the KEAP1-NRF2 system to the prevention and attenuation of physiological aging and aging-related diseases. Accumulating knowledge to control stress-induced damage may provide a clue for extending healthspan and treating aging-related diseases. In this review, we focus on the relationships between oxidative stress and aging-related alterations in the sensory, glandular, muscular, and central nervous systems and the roles of the KEAP1-NRF2 system in aging processes.

Сell death and its significance in reproductive pathology

Since the middle of the last century, scientists have been interested in the mechanisms of regulation of cell division, differentiation and aging of cells. The first objects of study were insects, helminths and other living organisms. From the very beginning, in the biology of cell development and regulation, scientists have attached leading importance to genetic factors. Later, more and more experience was gained on the influence of intracellular factors, metabolic changes and exogenous pathogens on the programmed cell death. Recent research on cell biology and pathology has focused on the study of apoptosis. The first described phenomenon of programmed cell death was apoptosis. Subsequent studies were aimed at the study programmed cell death. This review will provide an opportunity to consider the biological mechanisms of programmed cell death, differences and species characteristics. The author described the clinical aspects of apoptosis, necroptosis and pyroptosis and their importance in the formation of cellular homeostasis. In the present review article simple classification system, where the cell death entities are primarily categorized into programmed cell death. Multiple mechanisms and phenotypes compose programmed non-apoptotic cell death, including: autophagy, entosis, methuosis and paraptosis, mitoptosis and parthanatos, ferroptosis, pyroptosis NETosis and necroptosis. Changes of cellular regulation at development of pathologies at people and animals are considered. Cell biology includes a variety of mechanisms of programmed aging and death. Modern research is aimed at deepening the study multiple mechanisms and phenotypes compose programmed. Cells. will certainly be taken into account by the Nomenclature Committee on Cell Death. Cellular regulation is associated with a variety of physiological mechanisms of development, and is also important in processes such as inflammation, immune response, embryogenesis maintenance of tissue homeostasis. Study of factors of influence and mechanisms of regulation of aging of cells opens a curtain for development of the newest means of diagnostics of pathologies and development of pharmacological means for correction of cellular mechanisms at development of pathologies.

Building, testing, and learning from network models of human aging

We have developed computational models of human aging that are based on complex networks of interactions between health attributes of individuals. Our “generic network model” (GNM) captures the population level exponential increase of mortality with age in Gompertz’s law together with the exponential decrease of health as measured by the frailty index (FI). Our GNM includes only random accumulation of damage, with no programmed aging. Our GNM allows large populations of model individuals to be quickly generated with detailed individual health trajectories. This allows us to explore individual damage propagation in detail. To facilitate comparison with observational data, we have also developed and tested new approaches to binarizing continuous-valued health data. To extract the most information out of available cross-sectional or longitudinal data, we have also reconstructed interactions from generalized network models that can predict individual health trajectories and mortality.

The Mechanism of Programmed Aging: The Way to Create a Real Remedy for Senescence

Background: Accumulation of various damages is considered the primary cause of aging throughout the history of gerontology. No progress has been made in extending animal lifespan under the guidance of this concept. This concept denies the existence of longevity genes, but it has been experimentally shown that manipulating genes that affect cell division rates can increase the maximum lifespan of animals. These methods of prolonging life are unsuitable for humans because of dangerous side effects, but they undoubtedly indicate the programmed nature of aging. Objective: The objective was to understand the mechanism of programmed aging to determine how to solve the problem of longevity. Methods: Fundamental research has already explored key details relating to the mechanism of programmed aging, but they are scattered across different fields of knowledge. The way was to recognize and combine them into a uniform mechanism. Results: Only a decrease in bioenergetics is under direct genetic control. This causes many different harmful processes that serve as the execution mechanism of the aging program. The aging rate and, therefore, lifespan are determined by the rate of cell proliferation and the magnitude of the decrease in bioenergetics per cell division in critical tissues. Conclusion: The mechanism of programmed aging points the way to achieving an unlimited healthy life; it is necessary to develop a means for managing bioenergetics. It has already been substantially studied by molecular biologists and is now waiting for researchers from gerontology.