Longitudinal associations between dietary inflammatory index and musculoskeletal health in community-dwelling older adults

Background & Aims: Aging is characterized by progressive decline in physiologic reserves and functions as well as prolonged inflammation, increasing susceptibility to disease. Diet plays an important role in maintaining health, and reducing morbidity and mortality, especially in older populations. This study was designed to determine prospective associations between dietary inflammatory index (DII®) scores and bone health, sarcopenia-related outcomes, falls risk and incident fractures in community-dwelling Australian older adults.Methods: A total of 1098 [51% male; age (mean ± SD) 63.0 ± 7.5 years] non-institutionalized older adults who participated in the Tasmanian Older Adult Cohort Study (TASOAC) at baseline, 768 at 5 years, and 566 at 10 years follow-up were included in this analysis. Baseline energy-adjusted DII (E-DII) scores were calculated using a validated Food Frequency Questionnaire. Changes in bone mineral density (BMD) and appendicular lean mass (ALM) were measured over ten years using dual-energy x-ray absorptiometry. Ten-year changes in hand grip, knee extensor and whole lower-limb muscle strength and quality were assessed by dynamometers and change in falls risk score using the Physical Profile Assessment (PPA). Incident fractures at any site and non-vertebral fractures over 10 years were self-reported.Results: The E-DII range was -3.48 to +3.23 in men and -3.80 to +2.74 in women. Higher E-DII score (indicating a more pro-inflammatory diet) was associated with lower total hip (B: -0.009; 95% CI: -0.017, 0.000) and lumbar spine BMD (B: -0.013; 95% CI: -0.024, -0.002), and higher falls risk score (B: 0.040; 95% CI: 0.002, 0.078) over 10 years in men. Women with higher E-DII scores had higher whole lower-limb muscle quality over 10 years (B: 0.109; 95% CI: 0.002, 0.215). For every unit increase in E-DII score, incident fracture rates increased by 9.0% in men (IRR: 1.090; 95% CI: 1.011, 1.175) and decreased by 12.2% in women (IRR: 0.878; 95% CI: 0.800, 0.964) in a fully adjusted model.Conclusion: Higher E-DII scores were associated with lower bone density, higher falls risk, and increased incidence of fractures in community-dwelling older men, but decreased fracture incidence in women, over 10 years. This suggests pro-inflammatory diets may be more detrimental to musculoskeletal health in older men than in women. Additional studies are warranted to elucidate these sex differences

A miR-34a-SIRT6 axis in the squamous cell differentiation network

Squamous cell carcinomas (SCCs) are highly heterogeneous tumours, resulting from deranged expression of genes involved in squamous cell differentiation. Here we report that microRNA-34a (miR-34a) functions as a novel node in the squamous cell differentiation network, with SIRT6 as a critical target. miR-34a expression increases with keratinocyte differentiation, while it is suppressed in skin and oral SCCs, SCC cell lines, and aberrantly differentiating primary human keratinocytes (HKCs). Expression of this miRNA is restored in SCC cells, in parallel with differentiation, by reversion of genomic DNA methylation or wild-type p53 expression. In normal HKCs, the pro-differentiation effects of increased p53 activity or UVB exposure are miR-34a-dependent, and increased miR-34a levels are sufficient to induce differentiation of these cells both in vitro and in vivo. SIRT6, a sirtuin family member not previously connected with miR-34a function, is a direct target of this miRNA in HKCs, and SIRT6 down-modulation is sufficient to reproduce the miR-34a pro-differentiation effects. The findings are of likely biological significance, as SIRT6 is oppositely expressed to miR-34a in normal keratinocytes and keratinocyte-derived tumours