Publications

Huntington's disease (HD) is a fatal inherited neurodegenerative disorder. HD is caused by polyglutamine expansions in the huntingtin (htt) protein that result in neuronal loss and contribute to HD pathology. The mechanisms of neuronal loss in HD are elusive, and there is no therapy to alleviate HD. To find small molecules that slow neuronal loss in HD, we screened 1,040 biologically active molecules to identify suppressors of cell death in a neuronal cell culture model of HD. We found that inhibitors of mitochondrial function or glycolysis rescued cell death in this cell culture and in in vivo HD models. These inhibitors prevented cell death by activating prosurvival ERK and AKT signaling but without altering cellular ATP levels. ERK and AKT inhibition through the use of specific chemical inhibitors abrogated the rescue, whereas their activation through the use of growth factors rescued cell death, suggesting that this activation could explain the protective effect of metabolic inhibitors. Both ERK and AKT signaling are disrupted in HD, and activating these pathways is protective in several HD models. Our results reveal a mechanism for activating prosurvival signaling that could be exploited for treating HD and possibly other neurodegenerative disorders.

OBJECTIVES

To investigate whether underweight, normal-weight, overweight, and obese older adults differ in aspects of their oral health-related quality of life (OHRQoL).

DESIGN

Cross-sectional study using a 54-item OHRQoL questionnaire.

SETTING

Five counties in central Alabama: Jefferson and Tuscaloosa (urban), and Hale, Bibb, and Pickens (rural).

PARTICIPANTS

The 291 subjects were recruited from participants in the University of Alabama at Birmingham Study of Aging, a longitudinal study of mobility. Participants ranged in age from 65 to 90 (60.5% women, 50.5% non-Hispanic white, and 50.5% rural).

MEASUREMENTS

Participants completed an in-home interview about their OHRQoL using a 54-item questionnaire and were classified into four categories of body mass index (BMI) (<20.0 (underweight), 20.0-24.9 (normal), 25.0-29.9 (overweight), and >/=30.0 (obese)). Multivariate analyses were used to examine associations between BMI and OHRQoL, adjusting for age, race, sex, depression, education, perceived income, comorbidity score, life-space mobility, and physical activity level.

RESULTS

The results suggested that a parabolic effect existed, with strongest associations occurring in the underweight and obese categories. With the normal BMI group as the reference group, obese participants were more likely to avoid eating foods they would like to eat, overweight participants were less likely to cook foods differently and reported better chewing ability, and underweight persons were more likely to limit foods they eat because of mouth dryness.

CONCLUSION

Objective measures may not accurately reflect peoples' perceptions; therefore, OHRQoL determined according to response to subjective questions is important to properly assess a patient's overall health status. Older adults who are under- or overweight should be evaluated for oral health conditions that may affect their nutritional status.

In cultured human keratinocytes or murine epidermis, peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) (NR1C2) activators (1) stimulate keratinocyte differentiation; (2) decrease keratinocyte proliferation; (3) accelerate permeability barrier repair; (4) increase epidermal lipid synthesis; and (5) reduce cutaneous inflammation. Since these results suggest that PPARbeta/delta could play an important role in cutaneous homeostasis, we assessed here the skin phenotype of mice deficient in PPARbeta/delta. Gross cutaneous abnormalities were not evident, and both stratum corneum (SC) skin hydration and surface pH were normal. However, the epidermis was thickened and proliferating cell nuclear antigen (PCNA) staining was increased, indicating increased cell proliferation. No change in apoptosis was observed but the expression of differentiation markers, such as filaggrin, involucrin, and loricrin, was slightly increased in PPARbeta/delta(-/-) mice. Although basal permeability barrier function was normal, PPARbeta/delta knockout (KO) mice show a significant delay in barrier recovery rates following acute barrier disruption by either acetone treatment or tape-stripping. Delayed barrier recovery correlated with decreased production and secretion of lamellar bodies (LBs), and with reduced numbers of extracellular lamellar membranes in the SC. Finally, PPARbeta/delta KO mice displayed increased inflammation in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. Together, these results further demonstrate that PPARbeta/delta in the epidermis: (1) is required for permeability barrier homeostasis; (2) regulates keratinocyte proliferation; and (3) modulates cutaneous inflammation.

Childhood socioeconomic status (SES) acts over a lifetime to influence adult health outcomes. Whether the impact of childhood SES differs by age or race/ethnicity is unclear. The authors studied 20,566 community-living US adults aged > or =50 years. Parental education was the main predictor. Outcomes evaluated (1998-2002) included self-reported health and functional limitation. The influence of childhood SES on later-life health was also examined in groups stratified by age and race/ethnicity, with adjustment for demographic factors and current SES. Participants' mean age was 67 years; 57% were women. By race/ethnicity, 76% were White, 14% were Black, and 8% were Latino. The relation between low parental education and fair/poor self-rated health declined with advancing age (age 50-64 years: adjusted odds ratio (AOR) = 1.42, 95% confidence interval (CI): 1.24, 1.63; age > or =80 years: AOR = 1.14, 95% CI: 0.96, 1.36). The relation between low parental education and fair/poor self-rated health differed across racial/ethnic groups and was significant in White (AOR = 1.33, 95% CI: 1.21, 1.47) and Black (AOR = 1.37, 95% CI: 1.14, 1.64) participants but not Latinos. These findings suggest that childhood SES affects health status through midlife but the effects may abate in late life; its effects also may be weaker in Latinos than in Whites or Blacks.