Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance.

While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' are essential for insulin transfer across the liver sinusoidal endothelium and that age-related loss of fenestrations causes an impaired insulin clearance and hyperinsulinemia, induces hepatic insulin resistance, impairs hepatic insulin signaling, and deranges glucose homeostasis. To further define the role of fenestrations in hepatic insulin signaling without any of the long-term adaptive responses that occur with aging, we induced acute defenestration using poloxamer 407 (P407), and this replicated many of the age-related changes in hepatic glucose and insulin handling. Loss of fenestrations in the liver sinusoidal endothelium is a hallmark of aging that has previously been shown to cause deficits in hepatic drug and lipoprotein metabolism and now insulin. Liver defenestration thus provides a new mechanism that potentially contributes to age-related insulin resistance.

Impact of Longevity Interventions on a Validated Mouse Clinical Frailty Index.

This article investigates the effect on the mouse frailty index (FI), of factors known to influence lifespan and healthspan in mice: strain (short-lived DBA/2J mice vs long-lived C57BL/6J mice), calorie restriction (CR), and resveratrol treatment. The mouse FI, based on deficit accumulation, was recently validated in C57BL/6J mice by Whitehead JC, Hildebrand BA, Sun M, et al. (A clinical frailty index in aging mice: comparisons with frailty index data in humans. J Gerontol A Biol Sci Med Sci. 2014;69:621-632) and shares many characteristics of the human FI. FI scores were measured in male and female aged (18 months) ad-libitum fed and CR DBA/2J and C57BL/6J mice, as well as male aged (24 months) C57BL/6J mice ad-libitum fed with or without resveratrol (100 mg/kg/day) in the diet for 6 months. Mean scores of two raters were used, and the raters had excellent inter-rater reliability (ICC = 0.88, 95% CI [0.80, 0.92]). Furthermore, the interventions of CR and resveratrol were associated with a significant reduction in FI scores in C57BL/6J mice, compared to age-matched controls. The short-lived DBA/2J mice also had slightly higher FI scores than the C57BL/6J mice, for the male calorie-restricted groups (DBA/2J FI = 0.16±0.03, C57BL/6J FI = 0.11±0.03, p = .01). This study uses the mouse FI developed by Whitehead JC, Hildebrand BA, Sun M, et al. (A clinical frailty index in aging mice: comparisons with frailty index data in humans. J Gerontol A Biol Sci Med Sci. 2014;69:621-632) in a different mouse colony and shows that this tool can be applied to quantify the effect of dietary and pharmaceutical interventions on frailty.

The effects of group type and young silverbacks on wounding rates in western lowland gorilla (Gorilla gorilla gorilla) groups in North American zoos.

In North American zoos, male gorillas are often housed in all-male (bachelor) groups to provide socialization for males not managed in breeding groups. These groups exhibit long-term cohesion and stability and males in bachelor groups are no more aggressive than males in mixed-sex groups. Previous studies have shown that aggression in male gorillas is more directly related to age rather than group type, with young silverbacks (YSB; males 14-20 years of age) having higher rates of aggressive behavior than males of other age classes. Despite this, anecdotal reports have persisted that bachelor groups have higher wounding rates than mixed-sex groups. To assess wounding in zoo-housed gorillas, all instances of wounding across 28 zoos (180 gorillas, 45 social groups) were recorded over a 26 months period via a standardized data sheet. Similar to previous reports, we found age to be an important determinant in wounding. Bachelor groups that contained YSB's had significantly more wounds than bachelor groups without YSB's (U = 14.0, z = -2.193, P = 0.029). There was no difference in wounding rates between mixed-sex and bachelor groups without YSB's (U = 69.5, z = -0.411, P = 0.689). These data further demonstrate the importance of behavioral management of YSB's in zoos and the viability of bachelor groups as a long-term housing solution for male gorillas.