Increased burden of mitochondrial DNA deletions and point mutations in early-onset age-related hearing loss in mitochondrial mutator mice.

Mitochondrial DNA (mtDNA) mutations are thought to have a causal role in a variety of age-related neurodegenerative diseases, including age-related hearing loss (AHL). In the current study, we investigated the roles of mtDNA deletions and point mutations in AHL in mitochondrial mutator mice (Polgmut/mut) that were backcrossed onto CBA/CaJ mice, a well-established model of late-onset AHL. mtDNA deletions accumulated significantly with age in the inner ears of Polgmut/mut mice, while there were no differences in mtDNA deletion frequencies in the inner ears between 5 and 17 months old Polg+/+ mice or 5 months old Polg+/+ and Polgmut/mut mice. mtDNA deletions also accumulated significantly in the inner ears of CBA/CaJ mice during normal aging. In contrast, 5 months old Polgmut/mut mice displayed a 238-fold increase in mtDNA point mutation frequencies in the inner ears compared to age-matched Polg+/+ mice, but there were no differences in mtDNA point mutation frequencies in the inner ears between 5 and 17 months old Polgmut/mut mice. Seventeen-month-old Polgmut/mut mice also displayed early-onset severe hearing loss associated with a significant reduction in neural output of the cochlea, while age-matched Polg+/+ mice displayed little or no hearing impairment. Consistent with the physiological and mtDNA deletion test result, 17-month-old Polgmut/mut mice displayed a profound loss of spiral ganglion neurons in the cochlea. Thus, our data suggest that a higher burden of mtDNA point mutations from a young age and age-related accumulation of mtDNA deletions likely contribute to early-onset AHL in mitochondrial mutator mice.

The nutritional status and energy and protein intakes of MOW clients and the need for further targeted strategies to enhance intakes.

There is a paucity of literature about the nutritional status and energy and protein intakes of Meals on Wheels (MOW) clients. The current study aimed to determine the nutritional status and the adequacy of energy and protein intakes of MOW clients. Forty-two clients were recruited from two MOW services in the Illawarra region of Australia for assessment of their nutritional status, using the Mini Nutritional Assessment (MNA(®)). Estimated energy and protein intakes for a MOW day were compared to a non-MOW day and average daily energy and protein intakes were assessed against estimated daily requirements. A single dietitian performed all assessments and home based interviews to explore the client's perception of the service. Mean daily energy intake (7593 (±2012) kJ) was not significantly different to estimated requirements (7720 (±975) kJ) (P = 0.480), while mean daily protein intake was higher (78.7 (±23.4) g) than calculated requirements (68.4 (±10.8) g; P = 0.009). However 16 clients were identified as at risk of malnutrition and 2 were malnourished; consuming 2072 kJ (P = 0.000) less energy and 20.4 g less protein (P = 0.004) per day compared to well-nourished clients. MOW clients are at risk of being poorly nourished and meals delivered by the service provide an important contribution to overall intakes. These findings support the need for regular nutrition screening and dietary monitoring in this high risk group, to identify those for whom additional strategies may be indicated.

Skeletal Muscle Inflammation Following Repeated Bouts of Lengthening Contractions in Humans.

Skeletal muscle responds to exercise-induced damage by orchestrating an adaptive process that protects the muscle from damage by subsequent bouts of exercise, a phenomenon called the repeated bout effect (RBE). The mechanisms underlying the RBE are not understood. We hypothesized that an attenuated inflammation response following a repeated bout of lengthening contractions (LC) would be coincidental with a RBE, suggesting a potential relationship. Fourteen men (n = 7) and women (n = 7) completed two bouts of lengthening contractions (LC) separated by 28 days. Muscle biopsies were taken before the first bout (B1) from the non-exercised leg, and from the exercised leg 2- and 27-d post-B1 and 2-d following the second bout (B2). A 29-plex cytokine array identified alterations in inflammatory cytokines. Immunohistochemistry quantified inflammatory cell infiltration and major histocompatibility complex class 1 (MHC-1). Muscle soreness was attenuated in the days following B2 relative to B1, indicating a RBE. Intramuscular monocyte chemoattractant protein (MCP1) and interferon gamma-induced protein 10 (IP10) increased following B2 relative to the pre-exercise sample (7-52 and 11-36 pg/ml, respectively p < 0.05). Interleukin 4 (IL4) decreased (26-13 pg/ml, p < 0.05) following B2 relative to the pre-exercise sample. Infiltration of CD68(+) macrophages and CD8(+) T-cells were evident following B2, but not B1. Moreover, CD8(+) T-cells were observed infiltrating apparently necrotic muscle fibers. No changes in MHC-1 were found. We conclude that inflammation is not attenuated following a repeated bout of LC and that CD8(+) T-cells may play a role in muscle adaptation following LC. Moreover, it appears that the muscle or the immune system becomes sensitized to an initial bout of damaging exercise such that inflammatory cell infiltration into the muscle is enhanced upon a repeated bout of damaging exercise.