Heat Shock Proteins in Benign Prostatic Hyperplasia and Prostate Cancer

Two out of three diseases of the prostate gland affect aging men worldwide. Benign prostatic hyperplasia (BPH) is a noncancerous enlargement affecting millions of men. Prostate cancer (PCa) in turn is the second leading cause of cancer death. The factors influencing the occurrence of BPH and PCa are different; however, in the course of these two diseases, the overexpression of heat shock proteins is observed. Heat shock proteins (HSPs), chaperone proteins, are known to be one of the main proteins playing a role in maintaining cell homeostasis. HSPs take part in the process of the proper folding of newly formed proteins, and participate in the renaturation of damaged proteins. In addition, they are involved in the transport of specific proteins to the appropriate cell organelles and directing damaged proteins to proteasomes or lysosomes. Their function is to protect the proteins against degradation factors that are produced during cellular stress. HSPs are also involved in modulating the immune response and the process of apoptosis. One well-known factor affecting HSPs is the androgen receptor (AR)—a main player involved in the development of BPH and the progression of prostate cancer. HSPs play a cytoprotective role and determine the survival of cancer cells. These chaperones are often upregulated in malignancies and play an indispensable role in tumor progression. Therefore, HSPs are considered as one of the therapeutic targets in anti-cancer therapies. In this review article, we discuss the role of different HSPs in prostate diseases, and their potential as therapeutic targets.

Correlation Between Nongenomic Action of C19-Steroids and COVID-19 Severity

The recent COVID-19 pandemic is the defining global health crisis of our time and little is known about this disease. It has been reported that advanced age is considered a major risk factor for COVID-19 complications, and data suggest that this disease is deadlier for men than women but these observations are currently unclear. Regarding androgen action, it has been shown that certain smooth muscles are a target for androgens by inducing an acute relaxing effect in airway and vascular tissues that is nongenomically mediated; likewise, androgens are capable of inducing genomic anti-inflammatory and nongenomic hypotensive responses. The aim of this report is to associate the relationship between COVID-19 and aging men as well as the comorbidities presented in this group of patients linked with androgen deficiency. Remarkably, the nongenomic mechanisms of androgens as potential protectors are reviewed. On this basis, it is suggested that hypotestosteronemia may be a risk factor for COVID-19 severity.

Astaxantin and Isoflavones Inhibit Benign Prostatic Hyperplasia in Rats by Reducing Oxidative Stress and Normalizing Ca/Mg Balance

Benign prostatic hyperplasia (BPH) is a common pathology among aging men. Despite the broad pharmacological interventions, the available remedies to treat BPH are yet not devoid of side effects. Herbal compounds are suggested to be an alternative option for the BPH treatment. In our study, we evaluated the effect of kudzu isoflavones and astaxanthin on the BPH animal model. The animals were randomly divided into five groups: control; testosterone-induced BPH group; and three BPH-induced groups, which received intragastrically for 28 days finasteride (5 mg/kg) as a positive control, isoflavones (200 mg/kg), and astaxanthin (25 mg/kg). BPH was induced by castration of animals and subsequent subcutaneous injections of prolonged testosterone (25 mg/kg). Prostate index and histology, biochemical parameters, and antioxidant activity were evaluated. A significant decrease in prostate weight, immunohistochemical markers, and normalization of prostate Ca/Mg ratio was found in all treatment groups. Astaxanthin treatment also resulted in decreased epithelial proliferation and normalized superoxide dismutase activity. In conclusion, both isoflavones and astaxanthin inhibited BPH development at a level comparable to finasteride in terms of prostate weight, prostatic epithelium proliferation, and prostate tissue cumulative histology score. These results suggest that isoflavones and especially astaxanthin could serve as a potential alternative therapy to treat BHP.

Vision Difficulty and Engagement in Care Among Aging Men Living With HIV

For aging adults living with HIV (AALH) who have complex medical care needs, vision impairment may be an added burden that may lead individuals to disengage from their own medical care. We examined the relationships of self-reported vision difficulty with indicators of care engagement: 1) adherence to HIV antiretroviral therapy (ART; defined as taking ≥95% of medications); 2) self-reported avoidance of medical care; 3) self-reported tendency to ask a doctor questions about care (> 2 questions at a medical visit). A modified version of the National Eye Institute vision function questionnaire was administered at three semi-annual visits (from October 2017 to April 2018) to assess difficulty performing vision-dependent tasks (no, a little, moderate to extreme difficulty). We included 1063 AALH participants (median age 60 years, 24% Black). Data were analyzed using repeated measures logistic regression with generalized estimating equations adjusted for fixed race, and at visit values for age, education level, depressive symptoms, alcohol use, and smoking status. Compared to no vision difficulty, those reporting moderate to extreme vision difficulty on at least one task (18%) had 1.95 times higher odds (95% CI: 1.36, 2.79) of having less than optimal ART adherence and 1.92 times higher odds [95% CI: 1.06, 3.47]) of avoiding necessary medical care, but 1.6 times higher odds [95%CI: 0.93, 2.72] of asking more questions. These findings suggest that vision impairment plays a role in medical care engagement among older adults living with HIV, and may contribute to poorer management of HIV and chronic comorbidities.

Pulmonary and Physical Function Limitations in Aging Men with and without HIV from the Multicenter AIDS Cohort Study

We sought to determine effects of age, HIV serostatus, and smoking on the associations between pulmonary function and physical function impairments using Multicenter AIDS Cohort Study data. Associations between physical function outcomes gait speed (m/sec) and grip strength (kg) with normalized pulmonary function tests (diffusion capacity for carbon monoxide (DLCO, n=1,048) and forced expiratory volume in one second (FEV1, n=1,029)) were examined. Adjusted mixed-effects models included interaction terms to assess effect modification. 574(55%) were HIV+, with median age 57(IQR=48,64) and mean cumulative smoking pack-years 12.2(SD=19.0). 349(33%) had impaired DLCO (<80% of predicted) and 130(13%) had impaired FEV1 (<80% of predicted). Participants with impaired DLCO had weaker grip strength than those with normal DLCO (estimate= -3.5[95% CI=-4.6,-2.4]kg; p<0.001). Participants with impaired DLCO had slower gait speed than those with normal DLCO (estimate= -0.04[95% CI= -0.06,-0.02]m/sec; p=0.002). Age modified the DLCO effect on gait (p-interaction=0.01) but not grip (p-interaction=0.09). The association between decreased DLCO and slower gait was more pronounced in older participants. Smoking or HIV serostatus did not significantly modify the DLCO effect on gait (all p-interaction≥0.14) or grip (p-interaction=0.74, p-interaction=0.058, respectively). As with DLCO, participants with impaired FEV1 had weaker grip strength (estimate=-3.0[95% CI= -4.7,-1.3]kg; p<0.001) than those with normal FEV1. FEV1 was not associated with gait speed(p=0.98). Age, HIV serostatus or smoking did not modify the associations between FEV1 and gait speed or grip strength (all p-interaction>0.05). Associations between lower DLCO/FEV1 and decreased physical function suggest that interventions to improve pulmonary function may also preserve physical function with aging.

Rats exhibit age-related mosaic loss of chromosome Y

Mosaic loss of the Y chromosome (LOY) is the most frequent chromosomal aberration in aging men and is strongly correlated with mortality and disease. To date, studies of LOY have only been performed in humans, and so it is unclear whether LOY is a natural consequence of our relatively long lifespan or due to exposure to human-specific external stressors. Here, we explored whether LOY could be detected in rats. We applied a locus-specific PCR and target sequencing approach that we used as a proxy to estimate LOY in 339 samples covering eleven tissues from young and old individuals. We detected LOY in four tissues of older rats. To confirm the results from the PCR screening, we re-sequenced 60 full genomes from old rats, which revealed that the Y chromosome is the sole chromosome with low copy numbers. Finally, our results suggest that LOY is associated with other structural aberrations on the Y chromosome and possibly linked to the mosaic loss of the X chromosome. This is the first report, to our knowledge, demonstrating that the patterns of LOY observed in aging men are also present in a rodent, and conclude that LOY may be a natural process in placental mammals.

Shaken Identities, Reserve Masculine Capital, and the Lived Experiences of Aging Men with Breast Cancer

A question that begs to be examined is: How does aging men’s discovery they have breasts as a result of their breast cancer diagnosis and having a breast removed through a mastectomy, affect their masculine subjectivities and practices, as they also go about also living with a life-threatening illness? The present study aimed to better understand how men come to live with the knowledge that they have both breasts and cancer. Interviews with seventeen men in the U.S. (mean age 62.8) with a breast cancer diagnosis, mastectomy, and, most often, post-surgical hormonal treatment uncovered stories of body-self disruption and identity dilemmas. All the men’s identities had been shaken. After their mastectomy, they were reminded every morning that the body reflected in the mirror differed significantly from who they once were. Their stories revealed strategic themes: how they lived with cancer by slightly modifying conventional masculinities; and how others interacted with them, with the exception of mammography technologists, in terms of their gender, not their atypical illness. Only a few men initially felt their breast cancer was a gendered stigma. Noticeable was how the historical era when diagnosed and the age of the man at diagnosis contextualized their illness stories. In this presentation, three cases are used to exemplify the men’s varied experiences with their non-normative bodies and their commonality in finding reserves of masculine capital to rebuke the existential loneliness of a man with breast cancer.

Aging Men and Masculinity Ideologies: Variance Composition of the MRNS-BF and Measurement Invariance by Men's Age

The construct traditional masculinity ideology (TMI, Levant & Richmond, 2016), like the construct dominant masculinities (Coles, 2009; Messerschmidt, 2019), refers to culturally-based principles about proper gender practices for men. The present study aimed to create a briefer and psychometrically stronger form of the Male Role Norms Scale (MRNS), a long-standing and important measure of TMI. Using an archival data set (N = 626) with men age 25 and older, the MRNS was shortened using a set of recommended practices. Confirmatory factor analysis and assessment of measurement invariance showed the resulting MRNS-BF satisfies good fit principles with configural, metric, yet not reliable scalar invariance for age. It is a 6-item measure whose common factor measures TMI through two dimensions that mimic tenets Brannon (1976) and Connell (1995) theorized as underlying principles of masculinity ideologies in Western cultures: Earning and maintaining Respect/status, and No sissy stuff/avoidance of femininity in gender practices. Mean scores importantly show perhaps generational, certainly age cohort differences – aging men differed from established and middle-aged men by more moderately endorsing norms that specify men must strive to earn others’ respect and the cultural emphasis on no sissy stuff. Younger age cohorts strongly adopted principles of gender equality. These observed differences must be interpreted with great caution, since the men in the three age groups did not seem to have a common zero point. Still, the MRNS-BF has good psychometric properties, and its brevity can assist future research on how gender guidelines influence aging men’s health decisions and behavior.

Mosaic loss of chromosome Y in aged human microglia.

Mosaic loss of chromosome Y (LOY) is a particularly common acquired structural mutation in the leukocytes of aging men and it has been shown to correlate with several age-related diseases including Alzheimer's disease (AD). To derive the molecular basis of LOY in brain cells, we create an integrated resource by aggregating data from 21 single-cell and single-nuclei RNA brain studies, yielding 763,410 cells to investigate the presence and cell-type specific burden of LOY. We created robust quantification metrics for assessing LOY, which were validated using a multi-modal dataset. Using this new resource and LOY-quantification approach, we found that LOY frequencies differed widely between CNS cell-types and individual donors. Among five common neural cell types, microglia were most affected by LOY (7.79%, n=41,949), while LOY in neurons was rare (0.48%, n=220,010). Differential gene expression analysis in microglia found 188 autosomal genes, 6 X-linked genes, and 11 pseudoautosomal genes, pointing to broad dysregulation in lipoprotein metabolism, inflammatory response, and antigen processing that coincides with loss of Y. To our knowledge, we provide the first evidence of LOY in the microglia, and highlight its potential roles in aging and the pathogenesis of neurodegenerative disorders such as AD.

A gyermekkori csonttörések kapcsolata az időskori osteoporosissal: véletlen vagy előrejelzés?

Összefoglaló. A gyermekek közel fele szenved el csonttörést. Ez lehet traumás esemény vagy a csontfejlődést megzavaró genetikus, hormonális vagy egyéb eltérés a csontváz bármely részén. A leggyakoribb azonban az enyhe trauma kapcsán jelentkező csuklótáji törés, amely többnyire a pubertas alatt fordul elő. A jelenség alapja, hogy a serdülés során átmenetileg elválik egymástól a csontok méretének gyors növekedése és a csonttömeg gyarapodása, ami a longitudinális növekedést kb. egy év késéssel követi. Az így kialakuló átmeneti csontgyengeség a gyermekkori csonttörés fő oka, aminek a hatásához az említett genetikai, hormonális és életmódi rendellenességek is csatlakozhatnak. A gyermekkorban előfordult kistraumás csonttörés a felnőtt férfiaknál az osteoporosisos csonttörések fokozott rizikójával jár, ezért szűrővizsgálati kérdésként is szolgál. Nők esetében ugyanez az összefüggés még bizonyításra vár. Orv Hetil. 2021; 162(42): 1687–1692. Summary. Bone fracture occurs nearly in half of the children. Some fractures are severe traumatic events while others are the results of genetic or hormonal or other alterations disturbing the normal development of bone. However, the majority of fractures are associated with a mild trauma, dominantly in the pubertal period. The basic pathology of the pubertal fractures is the transient deviation of peak velocity of height growth from the gain velocity of bone mass; the latter goes to peak 1 year later than height growth. This difference has been resulted in a physiologic but transient weakening of bones that can coincide with genetic, hormonal or life-style problems and all of these factors together may cause the increased fragility of the pubertal bone. Low-trauma fractures in childhood may be followed in high fracture risk of adult and aging men, so the childhood fracture seems to be a useful screening question for testing the osteoporosis in males. However, the same relation is still not proved in aging women. Orv Hetil. 2021; 162(42): 1687–1692.