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Dickerson, A.

Publications and source records attributed to Dickerson, A..

3 recordsLinked to original sources

High Intensity Interval Training in Aged Female Mice Preserves Physical, Cognitive, and Cardiovascular Function

BACKGROUNDAlong with advancing age comes declines in physical, cognitive, and cardiovascular function. This diminished capacity may lead to decreased ability to perform activities of daily living, disability onset, and loss of independence. Exercise is a regenerative medicine therapy that can mitigate this loss of function. High intensity interval training (HIIT) is an aerobic exercise paradigm consisting of intense activity periods interspersed with bouts of active recovery. Previously we demonstrated that HIIT preserved physical function in adult, middle-aged, and older male mice. However, whether HIIT preserves physical, cognitive, and cardiovascular function, mitigates frailty, and improves brain and heart health in older adult female mice remains unknown. HYPOTHESISCognitive, physical, and cardiovascular function in older adult female C57BL/6 will be preserved in exercised mice (HIIT) versus sedentary control (SED). METHODSMice (HIIT and SED, both n=9, 24m at end) were tested pre/post-intervention for physical (rotarod, treadmill, grip meter, inverted cling, voluntary wheel running, activity monitor), cognitive (open field, novel object recognition, puzzle box, y-maze), and cardiovascular (blood pressure, echocardiogram) function, body composition, and whole body calorimetry. The mice underwent 14-weeks of HIIT training with progressive volume and intensity. RESULTSHIIT significantly (p<0.05) increased or preserved function in many tests including: aerobic capacity (+71% HIIT versus, vs, no change, NC, in SED), four limb strength/endurance (-67% SED vs -28% HIIT), forelimb strength (-16% SED vs NC HIIT), overall motor function (NC SED vs +39% HIIT), executive function (NC SED vs +73% HIIT), and exploratory behavior, which improved across multiple tests with HIIT while remaining unchanged in SED. HIIT also reduced both systolic blood pressure by 12% (-17 mmHg) and mean arterial pressure by -16 mmHg. In addition, HIIT significantly reduced cardiac fibrosis, increased muscle fiber type 2a percentage, reduced IL-1{beta} expression in the hypothalamus, and mitigated frailty onset. CONCLUSIONHIIT significantly reduced age-related functional loss in all three domains assessed while preventing frailty onset in older adult females and improving markers of brain and heart health.

physiology↗

Heterogeny in cages: Age-structure and timing of attractant availability impacts fertile egg production in the black soldier fly, Hermetia illucens

Adult behavior is a growing area of interest for those researching the black soldier fly, Hermetia illucens (L.) (Diptera: Stratiomyidae), which is affected by underlying demography and spatiotemporal patterns. This greenhouse experiment examined the interaction of age-related effects that can accrue within heterogeneous breeding populations and the potential benefits of delaying an oviposition attractant in concert with restricting mean cohort age. The impetus for this investigation was because if flies are introduced into a mating-cage before old flies are removed or culled, this creates a population of mixed-age and mating-status. We hypothesized this potentially reduces quality among available mate choices, especially in small cages where flies might not be able to spatially segregate. Metrics for fitness included copulation frequency, oviposition frequency, weight of eggs produced, and hatch percentage. "Same"-aged cohorts (maximum 4-d-old at introduction) performed better than highly heterogeneous (1-16-d-old) "mixed" cohorts by mating 2.32-times more frequently and laying 6.58-times more eggs that were 1.17-times more fertile, despite 1.41 fewer observed oviposition events. Delaying the attractant had a significant effect on egg collection weight and led to 1.25-times higher egg yields for same- age populations compared to mixed-aged cohorts where the delaying the attractant had no significant effect. These results are likely due in part to an immediate desire to lay eggs by older females as well as haphazard egg laying in cage material, which was 2.09-times higher for mixed cohorts. The results highlight the importance of constraining the age of breeding populations and removing old adults from cages to improve yields and better manipulate behavior. For those for whom this is logistically unfeasible, providing an attractant box initially and continuously may be the preferred method to trap more eggs from heterogeneous populations.

ecology↗

Hypoxic memory of tumor intrinsic type I interferon suppression promotes breast cancer metastasis

Hypoxia is a common feature of many solid tumors due to aberrant proliferation and angiogenesis and has been associated with tumor progression and metastasis. Most of the well-known hypoxia effects are mediated through hypoxia-inducible factors (HIFs), but the long-lasting effect of hypoxia beyond the immediate HIF regulation remains less understood. Here we show that hypoxia exerts a prolonged effect to promote metastasis. Using breast cancer patient-derived circulating tumor cell (CTC) lines and common breast cancer cell lines, we found that hypoxia downregulates tumor intrinsic type I interferon (IFN) signaling and its downstream antigen presentation (AP) machinery in luminal breast cancer cells, via both HIF-dependent and HIF-independent mechanisms. Hypoxia induced IFN/AP suppression can last longer than the hypoxic exposure, presenting a "hypoxic memory" phenotype. Hypoxic memory of IFN/AP downregulation is established by specific hypoxic priming, and cells with hypoxic memory have an enhanced ability for tumorigenesis and metastasis. The histone deacetylase inhibitor (HDACi) Entinostat can erase the hypoxic memory and improve the immune clearance of tumor cells when combined with checkpoint immunotherapies in a syngeneic breast cancer mouse model. These results point to a novel mechanism for hypoxia facilitated tumor progression, through a long-lasting memory that provides advantages for CTCs during the metastatic cascade. Significance: We revealed a novel hypoxic memory of prolonged suppression of tumor intrinsic type I IFN and AP signals that promote tumorigenesis and metastasis, suggesting novel mechanistic understanding of the immune evasive properties of CTCs.

cancer biology↗