[Optimizing nutrition of older people as a mean of preventing premature aging].

The review presents data on the characteristics of construction of the diet of older persons. It is shown that inadequate nutrition is a significant risk factor for cardiovascular diseases, obesity, type 2 diabetes mellitus, gout and others that contribute to premature aging. Optimization of the diet should be considered as one of the areas of prevention and rehabilitation of these diseases and the prevention of premature aging. Attention is drawn to the age peculiar properties of the energy value of the diet, the content and the ratio of macronutrients in it. Modern data on the recommended daily intake of micronutrients -vitamins, minerals and trace elements for the elderly are presented. From the positions of the theory of oxidative stress, chronic inflammation and high-calorie nutrition, it is considered expedient to include products containing antioxidant ingredients: vitamins, trace elements and minor biologically active food components in the diet.

Vitamin E Supplementation Reduces Cellular Loss in the Brain of a Premature Aging Mouse Model.

BACKGROUND: Aging is a highly complex biological process driven by multiple factors. Its progression can partially be influenced by nutritional interventions. Vitamin E is a lipid-soluble anti-oxidant that is investigated as nutritional supplement for its ability to prevent or delay the onset of specific aging pathologies, including neurodegenerative disorders. PURPOSE: We aimed here to investigate the effect of vitamin E during aging progression in a well characterized mouse model for premature aging. METHOD: Xpg-/- animals received diets with low (~2.5 mg/kg feed), medium (75 mg/kg feed) or high (375 mg/kg feed) vitamin E concentration and their phenotype was monitored during aging progression. Vitamin E content was analyzed in the feed, for stability reasons, and in mouse plasma, brain, and liver, for effectiveness of the treatment. Subsequent age-related changes were monitored for improvement by increased vitamin E or worsening by depletion in both liver and nervous system, organs sensitive to oxidative stress. RESULTS: Mice supplemented with high levels of vitamin E showed a delayed onset of age-related body weight decline and appearance of tremors when compared to mice with a low dietary vitamin E intake. DNA damage resulting in liver abnormalities such as changes in polyploidy, was considerably prevented by elevated amounts of vitamin E. Additionally, immunohistochemical analyses revealed that high intake of vitamin E, when compared with low and medium levels of vitamin E in the diet, reduces the number of p53-positive cells throughout the brain, indicative of a lower number of cells dying due to DNA damage accumulated over time. CONCLUSIONS: Our data underline a neuroprotective role of vitamin E in the premature aging animal model used in this study, likely via a reduction of oxidative stress, and implies the importance of improved nutrition to sustain health.

Linking DNA damage, NAD(+)/SIRT1, and aging.

Diseases due to DNA damage repair machinery defects can resemble premature aging. In this issue of Cell Metabolism, Scheibye-Knudsen et al. (2014) demonstrate that increasing NAD(+) levels may reverse the inactivation of Sirt1 and mitochondrial defects in Cockayne Syndrome B that stem from nuclear NAD(+) depletion by the DNA repair protein PARP.

A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome.

Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair proteins CS group A or B (CSA or CSB). Since dietary interventions can alter neurodegenerative processes, Csb(m/m) mice were given a high-fat, caloric-restricted, or resveratrol-supplemented diet. High-fat feeding rescued the metabolic, transcriptomic, and behavioral phenotypes of Csb(m/m) mice. Furthermore, premature aging in CS mice, nematodes, and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, ß-hydroxybutyrate levels are increased by the high-fat diet, and ß-hydroxybutyrate, PARP inhibition, or NAD(+) supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB can displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, ß-hydroxybutyrate and NAD(+), through the deacetylase SIRT1 and suggests possible interventions for CS.

Premature ageing prevention: limitations and perspectives of pharmacological interventions.

A significant increase of the elderly in populations of developed countries is followed by increase morbidity and mortality from main age-related diseases--cardiovascular and neuro-degenerative, cancer, diabetes mellitus, declining in a resistance to infections. Obviously, the development of means of the prevention of the premature ageing and these diseases in humans are crucial at present. However, data on such type means rather scarce, contradictory and often not reliable from the points of view of the adequacy of the experiments to current scientific requirements, as well as the interpretation of the results and safety. Available data on the life span extension and adverse effects of chemical compounds and drugs suggested as geroprotectors are critically analyzed: antidiabetic drugs, growth and thyroid hormones, glucocorticoids, DHEA, sex steroids and contraceptives, melatonin and peptide preparations modulating the pineal gland, antioxidants, chelate agents and lathyrogens, adaptogens and herbs, neurotropic drugs, inhibitors of monoamine oxidase, immunomodulators and some other. Most of the results could not convincingly evidence the life span extension and safety of the suggested geroprotectors. We believe that it is necessary to establish an international program for the expert evaluation of the life span extension potential of pharmacological interventions for humans. The scope of the program should be to evaluate chemical, immunological, dietary and behavioural interventions that may lead to life span extension or retard premature ageing and the objective--preparation of critical reviews and evaluations on evidence of the life span extending properties of a wide range of potential geroprotectors and strategies by international groups of working experts. The program may assist national and international authorities in devising programs of health promotion and premature ageing prevention.