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Objective: To investigate whether and how a sedentary lifestyle contributes to knee osteoarthritis (OA) incidence and severity. Design: An experiment was conducted using Hartley guinea pigs, an established idiopathic knee OA model. To simulate a sedentary lifestyle, growing animals (n ¼ 18) were housed for 22 weeks in small cages that restricted their mobility, while another group of animals (n ¼ 17) received daily treadmill exercise to simulate moderate physical activity. After the experiment, histological assessments, biochemical assays, and mechanical testing were conducted to compare tibial articular cartilage structure, strength, and degree of OA degeneration between sedentary and physically active animals. Groups were also compared based on body weight and composition, as well as gut microbial community composition assessed using fecal 16S rRNA gene sequencing. Results: Prevalence of knee OA was similar between sedentary and physically active animals, but severity of the disease (cartilage lesion depth) was substantially greater in the sedentary group (P ¼ 0.02). In addition, during the experiment, sedentary animals developed cartilage with lower aggrecan quantity (P ¼ 0.03) and accumulated more body weight (P ¼ 0.005) and visceral adiposity (P ¼ 0.007). Groups did not differ greatly, however, in terms of cartilage thickness, collagen quantity, or stiffness, nor in terms of muscle weight, subcutaneous adiposity, or gut microbial community composition. Conclusions: Our findings indicate that a sedentary lifestyle promotes the development of knee OA, particularly by enhancing disease severity rather than risk of onset, and this potentially occurs through multiple pathways including by engendering growth of functionally deficient joint tissues and the accumulation of excess body weight and adiposity.

Objectives: Sodium, a vital micronutrient that is often in scarce supply for tropical herbivores, is sometimes found at high concentration in decaying wood. We tested two hypotheses for chimpanzees: first, that wood-eating facilitates acquisition of sodium; second, that wood-eating occurs in response to the low availability of sodium from other dietary sources. Materials and Methods:We studied the behavior of more than 50 chimpanzees of all age-sex classes in the Kanyawara community of Kibale National Park, Uganda. We quantified the sodium content of dietary items, including wood samples from tree species that chimpanzees consumed or did not consume. To assess variation in sodium intake, we used 7 years of data on time spent feeding on plant foods, 18 months of data on rates of food intake by adult females, and 20 years of data on meat-eating.Results: Major dietary sources of sodium were wood, fruits and meat. Chimpanzees consumed wood primarily from decaying trees of Neoboutonia macrocalyx (Euphorbiaceae), which had substantially higher sodium content than all other dietary items tested. Wood-eating was negatively correlated with fruit-eating. Females ate wood more often than males, while males had a greater probability of consuming meat at predation events.Discussion: We propose that females ate wood more often than males because females had reduced access to meat, their preferred source of sodium. This hypothesis suggests that the need for sodium is a motivating reason for chimpanzees to consume both meat and wood. K E Y W O R D S dietary salt, Kibale National Park, meat-eating, nutritional ecology, sex differences

Calorie restriction (CR) extends lifespan and retards age-related chronic diseases in most species. There is growing evidence that the gut microbiota has a pivotal role in host health and age-related pathological conditions. Yet, it is still unclear how CR and the gut microbiota are related to healthy aging. Here, we report findings from a small longitudinal study of male C57BL/6 mice maintained on either ad libitum or mild (15%) CR diets from 21 months of age and tracked until natural death. We demonstrate that CR results in a significantly reduced rate of increase in the frailty index (FI), a well-established indicator of aging. We observed significant alterations in diversity, as well as compositional patterns of the mouse gut microbiota during the aging process. Interrogating the FI-related microbial features using machine learning techniques, we show that gut microbial signatures from 21-month-old mice can predict the healthy aging of 30-month-old mice with reasonable accuracy. This study deepens our understanding of the links between CR, gut microbiota, and frailty in the aging process of mice.