Increased Skeletal Muscle 11βHSD1 mRNA Is Associated with Lower Muscle Strength in Ageing

Background: Sarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC) in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR) signaling by increased expression of either GR or the GC-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) in muscle. Methods: There were 82 participants; group 1 comprised 33 older men (mean age 70.2years, SD 4.4) and 19 younger men (22.2years, 1.7) and group 2 comprised 16 older men (79.1years, 3.4) and 14 older women (80.1years, 3.7). We measured muscle strength, mid-thigh cross-sectional area, fasting morning plasma cortisol, quadriceps muscle GR and 11βHSD1 mRNA, and urinary glucocorticoid metabolites. Data were analysed using multiple linear regression adjusting for age, gender and body size. Results: Muscle strength and size were not associated with plasma cortisol, total urinary glucocorticoids or the ratio of urinary 5β-tetrahydrocortisol +5α-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11βHSD activity). Muscle strength was associated with 11βHSD1 mRNA levels (β -0.35, p = 0.04), but GR mRNA levels were not significantly associated with muscle strength or size. Conclusion: Although circulating levels of GC are not associated with muscle strength or size in either gender, increased cortisol generation within muscle by 11βHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11βHSD1 may have therapeutic potential in sarcopenia

Maintenance of T cell function in the face of chronic antigen stimulation and repeated reactivation for a latent virus infection.

Persisting infections are often associated with chronic T cell activation. For certain pathogens, this can lead to T cell exhaustion and survival of what is otherwise a cleared infection. In contrast, for herpesviruses, T cells never eliminate infection once it is established. Instead, effective immunity appears to maintain these pathogens in a state of latency. We used infection with HSV to examine whether effector-type T cells undergoing chronic stimulation retained functional and proliferative capacity during latency and subsequent reactivation. We found that latency-associated T cells exhibited a polyfunctional phenotype and could secrete a range of effector cytokines. These T cells were also capable of mounting a recall proliferative response on HSV reactivation and could do so repeatedly. Thus, for this latent infection, T cells subjected to chronic Ag stimulation and periodic reactivation retain the ability to respond to local virus challenge

The aetiology and trajectory of anabolic-androgenic steroid use initiation: a systematic review and synthesis of qualitative research

Background: To our knowledge, there has never been a systematic review and synthesis of the qualitative literature on the trajectory and aetiology of nonmedical anabolic-androgenic steroid (AAS) use. Methods: We systematically reviewed and synthesized qualitative literature gathered from searches in PsycINFO, PubMed, ISI Web of Science, Google Scholar, and reference lists of relevant literature to investigate AAS users’ ages of first use and source(s), history prior to use, and motives/drives for initiating use. We adhered to the recommendations of the UK Economic and Social Research Council’s qualitative research synthesis manual and the PRISMA guidelines. Results: A total of 44 studies published between 1980 and 2014 were included in the synthesis. Studies originated from 11 countries: the United States (n =18), England (n =8), Australia (n =4), Sweden (n =4), both England and Wales (n =2), and Scotland (n =2). One study each originated from Brazil, Bulgaria, Canada, France, Great Britain, and Norway. The majority of AAS users initiated use before age 30. Sports participation (particularly power sports), negative body image, and psychological disorders such as depression preceded initiation of AAS use for most users. Sources of first AAS were mainly users’ immediate social networks and the illicit market. Enhanced sports performance, appearance, and muscle/strength were the paramount motives for AAS use initiation. Conclusions: Our findings elucidate the significance of psychosocial factors in AAS use initiation. The proliferation of AAS on the illicit market and social networks demands better ways of dealing with the global public health problem of AAS use