Age Related Diseases

Aging is a multifactorial process resulting in several functional and esthetic changes in the skin. Advances in research have yielded a tremendous amount of information on the molecular pathways involved in both intrinsic aging (natural) and extrin-sic aging (including photoaging). Some of the characteristic features of aging skin, such as wrinkling, loss of elasticity, and atrophy, can largely be attributed to dermal changes. The amount of collagen in the skin decreases, while the cross linking increases, and the solubility of collagen is reduced. The role of fibroblasts in aging tissue has been most extensively studied in mammalian skin. The total number of fibroblasts decreases, and their metabolism shows characteristic alterations.The dermis is maintained in large part by fibroblasts, which secrete dermal collagens, elastin, and other extracellular matrix components. When the skin is wounded, fibroblasts secrete proteases to degrade the wounded matrix, and then synthesize new matrix. The fibroblasts also secrete growth factors to stimulate the keratinocytes to proliferate and close the wound and cytokines to attract macrophages to engulf and degrade debris. Stress-induced premature senescence (SIPS) occurs after many different sublethal stresses including a number of oxidation factors, such as H 2 O 2 , hyperoxia, or organic and lipid hydroperoxides. Fibroblast cells in replicative senescence share common features with cells in SIPS: morphology, senescence-associated beta-galactosidase activity , cell cycle regulation, gene expression and telomere shortening. Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. We systematically examine the evidence supporting the use of dosage forms of non-hydrolized carnosine or carcinine in oral formulations for skin beautification purposes and provide a summary of the biomarkers of intrinsic and extrinsic skin aging, including pho-toaging. Senescence phenotype of human diploid fibroblasts is related with the exhaustion of their proliferative potential. This work suggests that different cell types, such as human skin fibroblasts, may use specific cellular treatment strategies with imidazole-containing dipeptides to halt the accelerated senescence of the fibroblast cells in response to telomere attrition and thus prevent skin aging through the number of biologically viable and safe metabolic pathways. The published data demonstrate that telomerase is expressed in the epidermis in situ independent of age. The reason for the sustained telomere length or expression of telomerase activity in the epidermis is associated not only with an increased turnover of keratinocytes, but also occurs due to the fact that the formation of a well structured epidermis strictly depends on a tight balance between proliferation and differentiation. Oral dosage forms of non-hydrolized carnosine or carcinine induce cellular responses in human skin fibroblasts through the telomere-mediated pathway and redox signaling, supporting the view that carnosine or related imidazole-containing dipeptide based compound-induced hormetic stimulation of cellular antioxidant defenses can be a useful approach toward anti-aging intervention to the skin.

The purpose of this review is to substantiate a new (yet hypothetical) approach to the treatment of age-dependent diseases, which consists in cleansing the body of aged cells with the help of senolytics and prevention of fibrosis by stimulating the replenishment of the formed “cleared” of old cells space with rejuvenated cells using a combination of ROCK inhibitor with 5-LOX inhibitor and palmitoylethanolamide.  It is assumed that this combination of drugs will work synergistically, causing conditional reprogramming of cells in situ and, as a consequence, proliferation of progenitor cells necessary to make up for losses.

Cell polarity is a universal biological phenomenon. While much is known about the establishment and maintenance of cell polarity, its role in aging and age-related diseases remains to be fully addressed. Nonetheless, the exciting findings in the budding yeast indicate that the polar processes are intimately linked to both aging of the mother cell and rejuvenation of the daughter cell. This includes polar segregation of damaged proteins and ERCs due to the septin-based diffusion barrier, asymmetric inheritance of MDR proteins and retrograde protein transport. The principal, still unexplored question is whether the same polar mechanisms work during the asymmetric division of germ and stem cells, allowing their rejuvenation across generations. Further strengthening the links between cell polarity and aging is a large number of common genes associated with both polarity and longevity. Given a strong similarity between mechanisms of cell polarity in yeast and higher eukaryotes, the budding yeast Saccharomyces cerevisiae could serve as a convenient model system for studying the links between the cell polarity, aging and rejuvenation. Consequently, exploring the potential mammalian equivalents of yeast-established polarity mechanisms could be the focus for future biogerontological investigations.

Although normal aging does not have a pernicious effect on the homeostasis of fluids, renal reserve in elderly people can be depleted. The purpose of the present study was to assess the relationship between longitudinal changes with age in basic urine parameters (specific gravity and pH) in older men and women, depending on their body height and relative body weight. Longitudinal data on these two quantitative traits of the urine were available for 142 physically healthy individuals, including 68 men and 74 women. All subjects were 45 years of age at the beginning and 70 at the end of the period under investigation. All measurements were taken in accordance with internationally accepted requirements. Specific gravity was assessed using a hydrometer, and pH was measured using a pH meter. ANOVA, t-test, and regression analysis were performed. No significant sex differences in specific gravity or urine pH were observed. In both sexes, urine specific gravity decreased with age according...

Although normal aging does not have a pernicious effect on the homeostasis of fluids, renal reserve in elderly people can be depleted. The purpose of the present study was to assess the relationship between longitudinal changes with age in basic urine parameters (specific gravity and pH) in older men and women, depending on their body height and relative body weight. Longitudinal data on these two quantitative traits of the urine were available for 142 physically healthy individuals, including 68 men and 74 women. All subjects were 45 years of age at the beginning and 70 at the end of the period under investigation. All measurements were taken in accordance with internationally accepted requirements. Specific gravity was assessed using a hydrometer, and pH was measured using a pH meter. ANOVA, t-test, and regression analysis were performed. No significant sex differences in specific gravity or urine pH were observed. In both sexes, urine specific gravity decreased with age according to exponential model of regression. In men, there was a gradual increase in the pH of the urine until age 65, and the best fitting regression model was polynomial. In women, on the other hand, there was an exiguous decrease in urine pH throughout the period under study, and the best fitting regression model proved to be exponential. As the process of renal aging commences relatively early in ontogeny and manifests itself in many structural and functional changes, urinalysis and other more sophisticated methods of diagnosis of renal diseases are essential for proper assessment of health status of adults and older individuals. The rate of age-related changes in the analyzed traits of the urine was commensurate in both sexes, thereby revealing no evidence of significant sex differences in terms of renal aging in the period between 45 and 70 years of age.

"The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling.
Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor.
Using modified aptamer-based proteomics, we identified the TGF-b superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging."

Although normal aging does not have a pernicious effect on the homeostasis of fluids, renal reserve in elderly people can be depleted. The purpose of the present study was to assess the relationship between longitudinal changes with age in basic urine parameters (specific gravity and pH) in older men and women, depending on their body height and relative body weight. Longitudinal data on these two quantitative traits of the urine were available for 142 physically healthy individuals, including 68 men and 74 women. All subjects were 45 years of age at the beginning and 70 at the end of the period under investigation. All measurements were taken in accordance with internationally accepted requirements. Specific gravity was assessed using a hydrometer, and pH was measured using a pH meter. ANOVA, t-test, and regression analysis were performed. No significant sex differences in specific gravity or urine pH were observed. In both sexes, urine specific gravity decreased with age according...

The morphology of the dorsal cochlear nucleus (DCN) was evaluated across the life span in inbred C57BL/6J (C57) and CBA/J (CBA) mice using 5 age groups (young adult to very old). C57 mice exhibit progressive cochlear sensorineural pathology and hearing loss during middle age; CBA mice have only modest sensorineural pathology late in life. DCN layers I, II, and III were evaluated histologically with serial sections stained for Nissl and fibers. DCN volume decreased with age in C57 mice, but the change began earliest and was most pronounced in layer III. In CBA mice, volume increased during the first year of life and decreased only in the oldest mice. All major DCN cell types were found in both strains at all ages. There was an age-related decrease in the mean size of neurons in C57 mice that was first observed in layer III. In CBA mice, only a nonsignificant trend toward smaller neurons was observed in the oldest mice. An age-related decline in the number of neurons in layer III (but not in layers I and II) occurred in C57 mice. Aged CBA mice exhibited no significant loss of DCN neurons. Thus, age-related changes in the DCN were much more pronounced in C57 mice than in CBA mice, and the changes in C57 mice were most pronounced in layer III. Because layer III receives most of the DCN's primary auditory input, it would be directly affected by age-related hearing loss and degeneration of spiral ganglion cells in C57 mice. This suggests that the age-related changes observed in DCN layer III of C57 mice are affected by progressive peripheral degenerative changes; when peripheral loss is minimal (CBA mice), less substantial age-related changes are observed. © 1992 Wiley-Liss, Inc.

Within the scenario of an increasing life expectancy worldwide it is mandatory to identify determinants of healthy aging. Centenarian offspring (CO) is one of the most informative model to identify trajectories of healthy aging and their determinants (genetic and environmental), being representative of elderly in their 70th whose lifestyle can be still modified to attain a better health. This study is the first comprehensive investigation of the health status of 267 CO (mean age: 70.2 years) and adopts the innovative approach of comparing CO with 107 age-matched offspring of non-long-lived parents (hereafter indicated as NCO controls), recruited according to strict inclusion demographic criteria of Italian population. We adopted a multidimensional approach which integrates functional and cognitive assessment together with epidemiological and clinical data, including pro- and anti-inflammatory cytokines and adipokines, lipid profile, and insulin resistance. CO have a lower prevalence...