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Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in the diseasome of aging; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysiology. A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success. These include administration of exogenous Klotho, synthetic and natural Klotho agonists and indirect approaches, via modulation of the foodome and the gut microbiota. All these approaches have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of aging.

Aging is the main risk factor for developing diabetes and other age-related diseases. One of the most common features of age-related comorbidities is the presence of low-grade chronic inflammation. This is also the case of metabolic syndrome and diabetes. At the subclinical level, a pro-inflammatory phenotype was shown to be associated with Type-2 diabetes mellitus (T2DM). This low to mid-grade inflammation is also present in elderly individuals and has been termed inflammaging. Whether inflammation is a component of aging or exclusively associated with age-related diseases in not entirely known. We used clinical data and biological readouts in a group of individuals stratified by age, diabetes status and comorbidities to investigate this aspect. While aging is the main predisposing factor for several diseases there is a concomitant increased level of pro-inflammatory cytokines. DM patients show an increased level of sTNFRll, sICAM-1, and TIMP-1 when compared to Healthy, Non-DM and Pre-DM individuals. These inflammatory molecules are also associated with insulin resistance and metabolic syndrome in Non-DM and pre-DM individuals. We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNFα, sTNFRI, and sTNFRII, when compared to other monotherapies. Longitudinal follow up indicates a higher proportion of death occurs in individuals taking other monotherapies compared to metformin monotherapy. Together our finding shows that chronic inflammation is present in healthy elderly individuals and exacerbated with diabetes patients. Likewise, metformin could help target age-related chronic inflammation in general, and reduce the predisposition to comorbidities and mortality.

The use of natural compounds as an alternative source of antimicrobials has become a necessity given the growing concern over global antimicrobial resistance. Polyphenols, found in various edible plants, offers one potential solution to this. We aimed to investigate the possibility of using curcumin within the context of oral health as a way of inhibiting and preventing the harmful development of Candida albicans biofilms. We undertook a series of adsorption experiments with varying concentrations of curcumin, showing that 50 μg/ml could prevent adhesion. This effect could be further synergized by the curcumin pre-treatment of yeast cells to obtain significantly greater inhibition (>90%, p < 0.001). Investigation of the biological impact of curcumin showed that it preferentially affected immature morphological forms (yeast and germlings), and actively promoted aggregation of the cells. Transcriptional analyses showed that key adhesins were down-regulated (ALS1 and ALS3), whereas aggregation related genes (ALS5 and AAF1) were up-regulated. Collectively, these data demonstrated that curcumin elicits anti-adhesive effects and that induces transcription of genes integrally involved in the processes related to biofilm formation. Curcumin and associated polyphenols therefore have the capacity to be developed for use in oral healthcare to augment existing preventative strategies for candidal biofilms on the denture surface.

Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in the diseasome of aging; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysiology. A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success. These include administration of exogenous Klotho, synthetic and natural Klotho agonists and indirect approaches, via modulation of the foodome and the gut microbiota. All these approaches have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of aging. [ABSTRACT FROM AUTHOR]

Taste and smell perceptions diminish in older age, impacting upon quality of life and nutrition, yet the causes of taste loss are largely unknown. Transient receptor potential channels (TRP) found on the oral mucosa are also involved in oral sensations including cooling and burning and may contribute to the eating experience of older people. Older adults often have reduced salivary flow and the physical properties of saliva may change, but the role of saliva in oral sensations of older adults is yet to be elucidated. Here, the effect of older age on subjective (perception) and objective (stimulated salivary response) measures of TRP stimulants, odors, and basic tastants was investigated. Whole mouth saliva was collected from younger (mean age 24 years) and older adults (mean age 72 years) following stimulation of taste [mono sodium glutamate (MSG) and caffeine], olfaction (menthol), and TRP receptors (capsaicin). Participants rated perceived intensity of each stimulus, and salivary properties were assessed. Older age was associated with 15% lower umami taste and 26% lower menthol odor perception, coupled with 17% lower salivary response to MSG. Interestingly, there were no differences for perception of TRP stimulants, so chemo-sensation was not affected by age. Younger adults had four times greater elasticity (Spinnbarkeit) with MUC7 levels almost double and 66% greater resting salivary flow rate. Stimulated salivary responses in the younger group were also higher compared to the older group, with changes in protein and viscoelasticity in response to taste and TRP stimulation. These results show the impact of older age upon taste and smell sensation which may lead to changes in the physical and compositional properties of saliva in response to taste/odor stimulation. Measurement of stimulated salivary flow and rheology provides an objective measure of taste in addition to subjective perceptions which can be influenced by participant bias. Chemo-sensation may be retained with age and trigeminal stimuli such as chili could be employed in future studies to enhance meals for an age group at risk of malnutrition. Alteration in salivary properties due to advanced age could impact on ability to taste due to poor diffusion of tastants and reduced oral surface protection. [ABSTRACT FROM AUTHOR]

Aging is the main risk factor for developing diabetes and other age-related diseases. One of the most common features of age-related comorbidities is the presence of low-grade chronic inflammation. This is also the case of metabolic syndrome and diabetes. At the subclinical level, a pro-inflammatory phenotype was shown to be associated with Type-2 diabetes mellitus (T2DM). This low to mid-grade inflammation is also present in elderly individuals and has been termed inflammaging. Whether inflammation is a component of aging or exclusively associated with age-related diseases in not entirely known. We used clinical data and biological readouts in a group of individuals stratified by age, diabetes status and comorbidities to investigate this aspect. While aging is the main predisposing factor for several diseases there is a concomitant increased level of pro-inflammatory cytokines. DM patients show an increased level of sTNFRll, sICAM-1, and TIMP-1 when compared to Healthy, Non-DM and Pre-DM individuals. These inflammatory molecules are also associated with insulin resistance and metabolic syndrome in Non-DM and pre-DM individuals. We also show that metformin monotherapy was associated with significantly lower levels of inflammatory molecules, like TNFα, sTNFRI, and sTNFRII, when compared to other monotherapies. Longitudinal follow up indicates a higher proportion of death occurs in individuals taking other monotherapies compared to metformin monotherapy. Together our finding shows that chronic inflammation is present in healthy elderly individuals and exacerbated with diabetes patients. Likewise, metformin could help target age-related chronic inflammation in general, and reduce the predisposition to comorbidities and mortality. [ABSTRACT FROM AUTHOR]

While dietary or supplementary antioxidants are thought to inhibit or delay oxidation of biological molecules, their utility in vivo has been marred by equivocal evidence. Consumption of polyphenol rich foods has been thought to alleviate postprandial oxidative stress and/or improve endothelial function. Although, previous studies suggested the utility of allantoin as a biomarker of oxidative stress, controlled dose response studies with dietary antioxidants to test this in humans have been limited. We therefore investigated the effects of 2 doses of polyphenol rich curry consumption on postprandial plasma concentrations of allantoin, allantoin to uric acid ratio, F2-isoprostanes using liquid chromatography-tandem mass spectrometry (LCMS-MS) and measured endothelial function using peripheral arterial tonometry (endoPAT). In a randomized controlled crossover trial in 17 non-smoking, healthy, Chinese men, aged 23.7 ± 2.4 years and BMI 23.1 ± 2.3 kg/m2, the volunteers consumed 3 test meals in a random order, consisting of either non-curry Dose 0 Control (D0C, 0 g spices), or Dose 1 Curry (D1C, 6 g spices) or Dose 2 Curry (D2C, 12 g spices), after overnight fast. There were significant reductions in postprandial allantoin concentrations (p < 0.001) and allantoin to uric acid ratio (p < 0.001) at 2 h and 3 h following test meal consumption, indicating improvements in postprandial redox balance with increasing curry doses, although there were no differences between treatments on F2-isoprostane concentrations or on RHI (measured at 2 h only). Allantoin may have a utility as a biomarker of redox balance, in an acute setting. The study was registered at www.clinicaltrials.gov (Identifier No. NCT02599272). [ABSTRACT FROM AUTHOR]

The use of natural compounds as an alternative source of antimicrobials has become a necessity given the growing concern over global antimicrobial resistance. Polyphenols, found in various edible plants, offers one potential solution to this. We aimed to investigate the possibility of using curcumin within the context of oral health as a way of inhibiting and preventing the harmful development of Candida albicans biofilms. We undertook a series of adsorption experiments with varying concentrations of curcumin, showing that 50 μg/ml could prevent adhesion. This effect could be further synergized by the curcumin pre-treatment of yeast cells to obtain significantly greater inhibition (>90%, p < 0.001). Investigation of the biological impact of curcumin showed that it preferentially affected immature morphological forms (yeast and germlings), and actively promoted aggregation of the cells. Transcriptional analyses showed that key adhesins were down-regulated (ALS1 and ALS3), whereas aggregation related genes (ALS5 and AAF1) were up-regulated. Collectively, these data demonstrated that curcumin elicits anti-adhesive effects and that induces transcription of genes integrally involved in the processes related to biofilm formation. Curcumin and associated polyphenols therefore have the capacity to be developed for use in oral healthcare to augment existing preventative strategies for candidal biofilms on the denture surface. [ABSTRACT FROM AUTHOR]