Relationship of the Behavior of Older Participants with Body Composition Change: Results of the Second Wave of the Cognition of Older People, Education, Recreational Activities, Nutrition, Comorbidities, and Functional Capacity Studies (COPERNICUS).

BACKGROUND: To examine the relationship between the frequency of physical activities and food product consumption with body composition change after two years in a sample of older people. METHODS: Body composition, mass change, frequency of physical activity, and food products consumption were measured. Depression severity, health self-assessment, cognitive function, and demographic data were included as confounders. RESULTS: There were no significant changes in body composition except for a reduction in visceral fat level within two years (p < 0.05). Drinking beer and eating sweets a few times per week were associated with a significant increase in body fat percentage (p < 0.05). Drinking green or white tea more frequently than a few times per year was related to an increase in body fat (3.18 to 3.88%, p < 0.05). Contrarily, daily consumption of coffee was related to a decrease in body fat (p = 0.029). Subjects who ate sweets once a week or more frequently consumed coffee more often. CONCLUSIONS: More frequent drinking of beer or of green or white tea and consumption of sweets were related to an increase in body fat percentage, while daily coffee consumption was related to a decrease in body fat percentage after two years in older, healthy subjects. Noteworthily, the frequencies of food product consumption are interrelated.

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.

Ex Vivo and In Vitro Antiaging and Antioxidant Extract Activity of the Amelanchier ovalis from Siberia.

Phenolic acids are biologically active substances that prevent aging and age-related diseases, e.g., cancer, cardiovascular diseases, Alzheimer's disease, Parkinson's disease, etc. Cellular senescence is related to oxidative stress. The Siberian Federal District is rich in medicinal plants whose extracts contain phenolic acids. These plants can serve as raw materials for antiaging, antioxidant food supplements, and Amelanchier ovalis is one of them. In the present research, we tested the phytochemical profile of its extract for phenolic acids. Its geroprotective and antioxidant properties were studied both ex vivo and in vitro using Saccharomyces cerevisiae Y-564 as a model organism. The chromotographic analysis revealed gallic, p-hydroxybenzoic, and protocatechuic acids, as well as derivatives of chlorogenic and gallic acids. The research involved 0.25, 0.5, and 1.0 mg/mL extracts of Amelanchier ovalis, all of which increased the growth and lifespan of yeast cells. In addition, the extracts increased the survival rate of yeast under oxidative stress. An in vitro experiment also demonstrated the antioxidant potential of Amelanchier ovalis against ABTS radicals. Therefore, the Amelanchier ovalis berry extract proved to be an excellent source of phenolic acids and may be recommended as a raw material for use in antioxidant and geroprotective food supplements.

Relevance of Bioassay of Biologically Active Substances (BAS) with Geroprotective Properties in the Model of the Nematode Caenorhabditis Elegans in In Vivo Experiments.

Aging is an inevitable process of nature. The age of living organisms contributes to the appearance of chronic diseases, which not only reduce the quality of life but also significantly damage it. Modern medicines can successfully fight multiple diseases and prolong life. At the same time, medications have a large number of side effects. New research indicates that bioactive phytochemicals have great potential for treating even the most severe diseases and can become an alternative to medicines. Despite many studies in this area, the effects of many plant ingredients on living organisms are poorly understood. Analysis of the mechanisms through which herbal preparations influence the aging process helps to select the right active substances and determine the optimal doses to obtain the maximum positive effect. It is preferable to check the effectiveness of plant extracts and biologically active components with geroprotective properties in vivo. For these purposes, live model systems, such as Rattusrattus, Musmusculus, Drosophila melanogaster, and Caenorhabditis elegans are used. These models help to comprehensively study the impact of the developed new drugs on the aging process. The model organism C. elegans is gaining increasing popularity in these studies because of its many advantages. This review article discusses the advantages of the nematode C. elegans as a model organism for studying the processes associated with aging. The influence of various BAS and plant extracts on the increase in the life span of the nematode, its stress resistance, and other markers of aging is also considered. The review shows that the nematode C.elegans has a number of advantages over other organisms and is a promising model system for studying the geroprotective properties of BAS.

Genome-Protecting Compounds as Potential Geroprotectors.

Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: 1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; 2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; 3) improving DNA damage response and repair; 4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

Discovery of fifteen new geroprotective plant extracts and identification of cellular processes they affect to prolong the chronological lifespan of budding yeast.

In a quest for previously unknown geroprotective natural chemicals, we used a robust cell viability assay to search for commercially available plant extracts that can substantially prolong the chronological lifespan of budding yeast. Many of these plant extracts have been used in traditional Chinese and other herbal medicines or the Mediterranean and other customary diets. Our search led to a discovery of fifteen plant extracts that significantly extend the longevity of chronologically aging yeast not limited in calorie supply. We show that each of these longevity-extending plant extracts is a geroprotector that decreases the rate of yeast chronological aging and promotes a hormetic stress response. We also show that each of the fifteen geroprotective plant extracts mimics the longevity-extending, stress-protecting, metabolic and physiological effects of a caloric restriction diet but if added to yeast cultured under non-caloric restriction conditions. We provide evidence that the fifteen geroprotective plant extracts exhibit partially overlapping effects on a distinct set of longevity-defining cellular processes. These effects include a rise in coupled mitochondrial respiration, an altered age-related chronology of changes in reactive oxygen species abundance, protection of cellular macromolecules from oxidative damage, and an age-related increase in the resistance to long-term oxidative and thermal stresses.

Pairwise combinations of chemical compounds that delay yeast chronological aging through different signaling pathways display synergistic effects on the extent of aging delay.

We have recently discovered six plant extracts that delay yeast chronological aging. Most of them affect different nodes, edges and modules of an evolutionarily conserved network of longevity regulation that integrates certain signaling pathways and protein kinases; this network is also under control of such aging-delaying chemical compounds as spermidine and resveratrol. We have previously shown that, if a strain carrying an aging-delaying single-gene mutation affecting a certain node, edge or module of the network is exposed to some of the six plant extracts, the mutation and the plant extract enhance aging-delaying efficiencies of each other so that their combination has a synergistic effect on the extent of aging delay. We therefore hypothesized that a pairwise combination of two aging-delaying plant extracts or a combination of one of these plant extracts and spermidine or resveratrol may have a synergistic effect on the extent of aging delay only if each component of this combination targets a different element of the network. To test our hypothesis, we assessed longevity-extending efficiencies of all possible pairwise combinations of the six plant extracts or of one of them and spermidine or resveratrol in chronologically aging yeast. In support of our hypothesis, we show that only pairwise combinations of naturally-occurring chemical compounds that slow aging through different nodes, edges and modules of the network delay aging in a synergistic manner.

Interventions for age-related diseases: Shifting the paradigm.

Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity. Here we review the state of the knowledge of multimorbidity, appraise the available evidence supporting the role of mechanisms of ageing in the development of the most common age-related diseases and assess potential molecules that may successfully target those key mechanisms.

08-4Balneotherapy and new natural remedies for healthy ageing / 日本温泉気候物理医学会雑誌

  Ageing is the major biomedical challenge of our society, considered as a progressive and irreversible set of structural and functional changes for a living organism, in relation with both genes and environmental factors. The percentage of elderly people and the incidence of age-related diseases such as cardio-vascular diseases, cancer and neurodegenerative diseases are main concerns for many scientists from worldwide. <BR>  Discovering the biological basis of ageing is one of the greatest remaining challenges for science. Findings from model organisms have revealed that ageing is a surprisingly modifiable process that can be manipulated by both genetic and environmental factors. <BR>  One well-studied dietary manipulation of ageing is caloric restriction, which consists of restricting the food intake of organisms without triggering malnutrition and has been shown to retard ageing in model organisms. Ageing is intrinsically complex, being driven by multiple causal mechanisms. Each mechanism tends to be partially supported by data indicating that it has a role in the overall cellular and molecular pathways underlying the ageing process. Pharmacological intervention to decelerate ageing and age-related diseases is highly attractive because it would target all the population during many years. If successful, healthy ageing therapy will be more efficient in reducing mortality than to fight separately each age-related disease. Research on healthy ageing interventions has evolved along the main theories of ageing.<BR>  Caloric restriction is already being used as a paradigm for developing compounds that mimic its life-extension effects and might therefore have therapeutic value. The potential for further advances in this field is immense; hundreds of genes in several pathways have recently emerged as regulators of ageing and caloric restriction in model organisms. Some of these genes, such as IGF1R and FOXO3, have also been associated with human longevity in genetic association studies. The parallel emergence of network approaches offers prospects to develop multitarget drugs and combinatorial therapies. Understanding how the environment modulates ageing-related genes may lead to human applications and disease therapies through diet, lifestyle, or pharmacological interventions. Unlocking the capacity to manipulate human ageing would result in unprecedented health benefits. Currently, health is understood as the removal of diseases in a defensive manner to the pathological process and with higher costs. Would be more effective the maintenance of health through prevention mechanisms identified by modern science. The study of the mechanisms by which various natural or health factors can influence the ageing process positively or negatively opens the path to design and obtain new products for the benefit of elderly people to maintain health for a long time and enabling a socially active role.<BR>  Combining the balneotherapy with using healthy-ageing products, provides a significant advantage and represents the sustainability of the research in the context of which spas are the ideal place for the application of new treatments. Peloids and plants, used in balneotherapy, in the treatment of various rheumatic, endocrine, dermatological or gynecological diseases, because of many biological, biochemical, physical, chemical and physico-chemical actions that have in the body - represent the support for the design of new geroprotectives.

08-4 Balneotherapy and new natural remedies for healthy ageing / 日本温泉気候物理医学会雑誌

  Ageing is the major biomedical challenge of our society, considered as a progressive and irreversible set of structural and functional changes for a living organism, in relation with both genes and environmental factors. The percentage of elderly people and the incidence of age-related diseases such as cardio-vascular diseases, cancer and neurodegenerative diseases are main concerns for many scientists from worldwide.   Discovering the biological basis of ageing is one of the greatest remaining challenges for science. Findings from model organisms have revealed that ageing is a surprisingly modifiable process that can be manipulated by both genetic and environmental factors.   One well-studied dietary manipulation of ageing is caloric restriction, which consists of restricting the food intake of organisms without triggering malnutrition and has been shown to retard ageing in model organisms. Ageing is intrinsically complex, being driven by multiple causal mechanisms. Each mechanism tends to be partially supported by data indicating that it has a role in the overall cellular and molecular pathways underlying the ageing process. Pharmacological intervention to decelerate ageing and age-related diseases is highly attractive because it would target all the population during many years. If successful, healthy ageing therapy will be more efficient in reducing mortality than to fight separately each age-related disease. Research on healthy ageing interventions has evolved along the main theories of ageing.   Caloric restriction is already being used as a paradigm for developing compounds that mimic its life-extension effects and might therefore have therapeutic value. The potential for further advances in this field is immense; hundreds of genes in several pathways have recently emerged as regulators of ageing and caloric restriction in model organisms. Some of these genes, such as IGF1R and FOXO3, have also been associated with human longevity in genetic association studies. The parallel emergence of network approaches offers prospects to develop multitarget drugs and combinatorial therapies. Understanding how the environment modulates ageing-related genes may lead to human applications and disease therapies through diet, lifestyle, or pharmacological interventions. Unlocking the capacity to manipulate human ageing would result in unprecedented health benefits. Currently, health is understood as the removal of diseases in a defensive manner to the pathological process and with higher costs. Would be more effective the maintenance of health through prevention mechanisms identified by modern science. The study of the mechanisms by which various natural or health factors can influence the ageing process positively or negatively opens the path to design and obtain new products for the benefit of elderly people to maintain health for a long time and enabling a socially active role.   Combining the balneotherapy with using healthy-ageing products, provides a significant advantage and represents the sustainability of the research in the context of which spas are the ideal place for the application of new treatments. Peloids and plants, used in balneotherapy, in the treatment of various rheumatic, endocrine, dermatological or gynecological diseases, because of many biological, biochemical, physical, chemical and physico-chemical actions that have in the body - represent the support for the design of new geroprotectives.