Andrew E. Mayes

Why Some Women Look Young for Their Age

The desire of many to look young for their age has led to the establishment of a large cosmetics industry. However, the features of appearance that primarily determine how old women look for their age and whether genetic or environmental factors predominately influence such features are largely unknown. We studied the facial appearance of 102 pairs of female Danish twins aged 59 to 81 as well as 162 British females aged 45 to 75. Skin wrinkling, hair graying and lip height were significantly and independently associated with how old the women looked for their age. The appearance of facial sun-damage was also found to be significantly correlated to how old women look for their age and was primarily due to its commonality with the appearance of skin wrinkles. There was also considerable variation in the perceived age data that was unaccounted for. Composite facial images created from women who looked young or old for their age indicated that the structure of subcutaneous tissue was partly responsible. Heritability analyses of the appearance features revealed that perceived age, pigmented age spots, skin wrinkles and the appearance of sun-damage were influenced more or less equally by genetic and environmental factors. Hair graying, recession of hair from the forehead and lip height were influenced mainly by genetic factors whereas environmental factors influenced hair thinning. These findings indicate that women who look young for their age have large lips, avoid sun-exposure and possess genetic factors that protect against the development of gray hair and skin wrinkles. The findings also demonstrate that perceived age is a better biomarker of skin, hair and facial aging than chronological age.

Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation

BackgroundStudies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans-10, cis-12 isomer, reduces body fat content. However, some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, and there are conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-γ (PPARγ) activation and expression. We have conducted three experiments with CLA in obese mice over three weeks, and one over eleven weeks. We have also investigated the effects of CLA isomers in PPARγ and PPARα reporter gene assays.ResultsInclusion of CLA or CLA enriched with its trans-10, cis-12 isomer in the diet of female genetically obese (lepob/lepob) mice for up to eleven weeks reduced body weight gain and white fat pad weight. After two weeks, in contrast to beneficial effects obtained with the PPARγ agonist rosiglitazone, CLA or CLA enriched with its trans-10, cis-12 isomer raised fasting blood glucose and plasma insulin concentrations, and exacerbated glucose tolerance. After 10 weeks, however, CLA had beneficial effects on glucose and insulin concentrations. At this time, CLA had no effect on the plasma TNFα concentration, but it markedly reduced the plasma adiponectin concentration. CLA and CLA enriched with either isomer raised the plasma triglyceride concentration during the first three weeks, but not subsequently. CLA enriched with its trans-10, cis-12 isomer, but not with its cis-9, trans-11 isomer, stimulated PPARγ-mediated reporter gene activity; both isomers stimulated PPARα-mediated reporter gene activity.ConclusionsCLA initially decreased but subsequently increased insulin sensitivity in lepob/lepob mice. Activation of both PPARγ and PPARα may contribute to the improvement in insulin sensitivity. In the short term, however, another mechanism, activated primarily by trans-10, cis-12-CLA, which probably leads to reduced adipocyte number and consequently reduced plasma adiponectin concentration, may decrease insulin sensitivity.

Perceived age as a biomarker of ageing: a clinical methodology

In a previous field-based study, how old one looks for one’s age (perceived age) was found to be predictive of mortality in elderly individuals. In conjunction, perceived age is of relevance and interest to the layperson. Here, a clinical methodology for generating perceived age as a biomarker of facial ageing is detailed. The methodology utilises facial photographs of subjects to present images to large numbers of age assessors who are primarily nationals of the country of study origin. In five observational studies in five different countries involving 874 female subjects it was found that subject age and assessor gender, nationality, age and ageing expertise had little effect on the perceived age data generated. However, increasing the numbers of age assessors up to 50 substantially increased the reproducibility of the mean perceived age for an image and a minimum of 10 assessors were required to give reproducible data. This methodology was also compared to a methodology that utilises passport-type photographs of subjects typically taken in field studies. Although the perceived age data from the two types of images were more similar to each other than to chronological age, there was a marked difference between the two sets of data. Therefore, to allow meaningful comparisons across perceived age studies, the same type of image should be used for the generation of perceived age. In conclusion, the methodology detailed here has demonstrated that perceived age can be a reproducible measure when large numbers of adult age assessors are used and can be utilised globally in studies to investigate facial ageing.

The impact of the catechol-O-methyltransferase genotype on vascular function and blood pressure after acute green tea ingestion

SCOPE Evidence for the benefits of green tea catechins on vascular function is inconsistent, with genotype potentially contributing to the heterogeneity in response. Here, the impact of the catechol-O-methyltransferase (COMT) genotype on vascular function and blood pressure (BP) after green tea extract ingestion are reported. METHODS AND RESULTS Fifty subjects (n = 25 of the proposed low-activity [AA] and of the high-activity [GG] COMT rs4680 genotype), completed a randomized, double-blind, crossover study. Peripheral arterial tonometry, digital volume pulse (DVP), and BP were assessed at baseline and 90 min after 1.06 g of green tea extract or placebo. A 5.5 h and subsequent 18.5 h urine collection was performed to assess green tea catechin excretion. A genotype × treatment interaction was observed for DVP reflection index (p = 0.014), with green tea extract in the AA COMT group attenuating the increase observed with placebo. A tendency for a greater increase in diastolic BP was evident at 90 min after the green tea extract compared to placebo (p = 0.07). A genotypic effect was observed for urinary methylated epigallocatechin during the first 5.5 h, with the GG COMT group demonstrating a greater concentration (p = 0.049). CONCLUSION Differences in small vessel tone according to COMT genotype were evident after acute green tea extract.

The impact of the catechol- O -methyltransferase genotype on the acute responsiveness of vascular reactivity to a green tea extract

The beneficial effects of green tea catechins, such as the proposed improvement in endothelial function, may be influenced by phase II metabolism during and after absorption. The methylation enzyme, catechol-O-methyltransferase (COMT), has a missense mutation rs4680 (G to A), proposed to result in a 40 % reduction in enzyme activity. In the present pilot study, twenty subjects (ten of each homozygous COMT genotype) were recruited. Green tea extract capsules (836 mg green tea catechins) were given in a fasted state, and a high-carbohydrate breakfast was given after 60 min. Blood samples and vascular function measurements were taken at regular intervals. The change in digital volume pulse stiffness index (SI) from baseline was shown to be different between genotype groups at 120 and 240 min, with a lower SI in the GG individuals (P ≤ 0·044). The change in blood pressure from baseline also differed between genotype groups, with a greater increase in systolic (P = 0·023) and diastolic (P = 0·034) blood pressure at 120 min in the GG group. The GG [corrected] group was shown to have a greater increase in insulin concentrations at 120 min (P = 0·019) and 180 min (P = 0·008) compared with baseline, despite similar glucose profiles. No genotypic differences were found in vascular reactivity measured using laser Doppler iontophoresis, total nitrite, lipids, plasma total antioxidant capacity or inflammatory markers after ingestion of the green tea extract. In conclusion, SI and insulin response to the glucose load differed between the COMT genotype groups, and this may be suggestive of a green tea extract and genotype interaction.

Identification of a novel agonist of peroxisome proliferator-activated receptors α and γ that may contribute to the anti-diabetic activity of guggulipid in Lepob/Lepob mice.

The ethyl acetate extract of the gum of the guggul tree, Commiphora mukul (guggulipid), is marketed for the treatment of dyslipidaemia and obesity. We have found that it protects Lep(ob)/Lep(ob) mice from diabetes and have investigated possible molecular mechanisms for its metabolic effects, in particular those due to a newly identified component, commipheric acid. Both guggulipid (EC(50)=0.82 microg/ml) and commipheric acid (EC(50)=0.26 microg/ml) activated human peroxisome proliferator-activated receptor alpha (PPARalpha) in COS-7 cells transiently transfected with the receptor and a reporter gene construct. Similarly, both guggulipid (EC(50)=2.3 microg/ml) and commipheric acid (EC(50)=0.3 microg/ml) activated PPARgamma and both promoted the differentiation of 3T3 L1 preadipocytes to adipocytes. Guggulipid (EC(50)=0.66 microg/ml), but not commipheric acid, activated liver X receptor alpha (LXRalpha). E- and Z-guggulsterones, which are largely responsible for guggulipids hypocholesterolaemic effect, had no effects in these assays. Guggulipid (20 g/kg diet) improved glucose tolerance in female Lep(ob)/Lep(ob) mice. Pure commipheric acid, given orally (960 mg/kg body weight, once daily), increased liver weight but did not affect body weight or glucose tolerance. However, the ethyl ester of commipheric acid (150 mg/kg, twice daily) lowered fasting blood glucose and plasma insulin, and plasma triglycerides without affecting food intake or body weight. These results raise the possibility that guggulipid has anti-diabetic activity due partly to commipheric acids PPARalpha/gamma agonism, but the systemic bioavailability of orally dosed, pure commipheric acid appears poor. Another component may contribute to guggulipids anti-diabetic and hypocholesterolaemic activity by stimulating LXRalpha.

Lifestyle and youthful looks

Lifestyle has been proven to have a dramatic effect on the risk of age‐related diseases. The association of lifestyle and facial ageing has been less well studied.

The action of a cosmetic hair treatment on follicle function

OBJECTIVE Human hair changes with age: fibre diameter and density decrease, hair growth slows and shedding increases. This series of controlled studies examined the effect on hair growth parameters of a new leave-on hair treatment (LOT) formulated with DynagenTM (containing hydrolysed yeast protein) and zinc salts. METHODS Hair growth data were collected from healthy women aged 18–65 years. The LOT’s effect on hair growth was measured in a randomized double-blind study and in hair samples; its effect on follicle-cell proliferation was assessed by quantifying Ki67 expression in scalp biopsies. The LOT’s effect on plucking force was determined in an ex vivo model. Dynagen’s effect on the expression of the tight-junction marker claudin-1 was analysed in cultured follicles. The effect on protease activity of zinc salts used in the LOT was examined in vitro. RESULTS Hair growth rate decreased with increasing subject age. The LOT significantly increased hair growth rate, fibre diameter, bundle cross-sectional area, Ki67 expression and the plucking force required to remove hair. Dynagen significantly increased claudin-1 expression in cultured follicles. Protease activity was reduced by zinc salts. CONCLUSION The Dynagen-based LOT increases hair-fibre diameter, strengthens the follicular root structure and increases hair growth rate.