While ruling out programmed aging, evolutionary theory predicts a quasi-program for aging, a continuation of the developmental program that is not turned off, is constantly on, becoming hyper-functional and damaging, causing diseases of aging Could it be switched off pharmacologically? This would require identification of a molecular target involved in cell senescence, organism aging and diseases of aging Notably, cell senescence is associated with activation of the TOR (target of rapamycin) nutrient- and mitogen-sensing pathway, which promotes cell growth, even though cell cycle is blocked Is TOR involved in organism aging? In fact, in yeast (where the cell is the organism), caloric restriction, rapamycin and mutations that inhibit TOR all slow down aging In animals from worms to mammals caloric restrictions, life-extending agents, and numerous mutations that increase longevity all converge on the TOR pathway And, in humans, cell hypertrophy, hyper-function and hyperplasia, typically associated with activation of TOR, contribute to diseases of aging Theoretical and clinical considerations suggest that rapamycin may be effective against atherosclerosis, hypertension and hyper-coagulation (thus, preventing myocardial infarction and stroke), osteoporosis, cancer, autoimmune diseases and arthritis, obesity, diabetes, macula-degeneration, Alzheimer's and Parkinson's diseases Finally, I discuss that extended life span will reveal new causes for aging (eg, ROS, 'wear and tear', Hayflick limit, stem cell exhaustion) that play a limited role now, when quasi-programmed senescence kills us first

Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition.

The epidemiology of benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS) has evolved considerably during the past several years. The term LUTS describes a distinct phenotype and allows for a broad epidemiologic description of urinary symptoms at a population level. Although it is becoming the preferred term for studying urinary symptoms in populations, LUTS remains interconnected with BPH in the literature. The incidence and prevalence of BPH and LUTS are increasing rapidly as the US population ages. BPH and LUTS are associated with serious medical morbidities, an increased risk of falls, depression, diminished health-related quality of life, and billions of dollars in annual health care costs. Although age and genetics play important roles in the etiology of BPH and LUTS, recent insights at the population level have revealed that modifiable risk factors are likely key components as well. Serum dihydrotestosterone, obesity, elevated fasting glucose, diabetes, fat and red meat intake, and inflammation increase the risk; vegetables, regular alcohol consumption, exercise, and NSAIDs decrease the risk.

/pdf/benign-prostatic-hyperplasia-and-male-lower-urinary-tract-4841dr3yej.pdf

Benign Prostatic Hyperplasia and Male Lower Urinary Tract Symptoms: Epidemiology and Risk Factors.

Modifiable Risk Factors for Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: New Approaches to Old Problems

Objectives To present historical and contemporary hypotheses on the pathogenesis of benign prostatic hyperplasia (BPH), and the potential implications for current medical therapies. Methods The literature on BPH was reviewed. BPH is a prevalent disease with significant health and economic impacts on patients and health organisations across the world, whilst the cause/initiation of the disease process has still not been fully determined. Results In BPH, pathways involving androgens, oestrogens, insulin, inflammation, proliferative reawakening, stem cells and telomerase have been hypothesised in the pathogenesis of the disease. A number of pathways first described >40 years ago have been first rebuked and then have come back into favour. A system of an inflammatory process within the prostate, which leads to growth factor production, stem cell activation, and cellular proliferation encompassing a number of pathways, is currently in vogue. This review also highlights the physiology of the prostate cell subpopulations and how this may account for the delay/failure in treatment response for certain medical therapies. Conclusion BPH is an important disease, and as the pathogenesis is not fully understood it impacts the effectiveness of medical therapies. This impacts patients, with further research potentially highlighting novel therapeutic avenues.

https://bjui-journals.onlinelibrary.wiley.com/doi/epdf/10.1111/bju.15229

Benign prostatic hyperplasia – what do we know?

Epidemiological data indicate that lower urinary tract symptoms (LUTS)/BPH can be associated with metabolic syndrome (MetS). Chronic inflammation has been proposed as a candidate mechanism at the crossroad between these two clinical entities. Aim of study is to examine the correlation among pre-operatory LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy specimens. A total of 271 consecutive men treated with simple prostatectomy were retrospectively selected for this study in two tertiary referral centers for LUTS/BPH. Prostate diameters and volume were measured by transrectal ultrasound, LUTS scored by International Prostate Symptom Score (IPSS) and obstruction by uroflowmetry. The International Diabetes Federation and American Heart Association and the National Heart, Lung and Blood Institute was used to define MetS. The inflammatory infiltrate was investigated combining anatomic location, grade and extent of flogosis into the overall inflammatory score (IS); the glandular disruption (GD) was used as a further marker. Eighty-six (31.7%) men were affected by MetS. Prostatic volume and anterior-posterior (AP) diameter were positively associated to the number of MetS components. Among MetS determinants, only dyslipidaemia (increased serum triglycerides and reduced serum high-density lipoprotein) was associated with an increased risk of having a prostatic volume >60 cm3 (hazard ratio (HR)=3.268, P<0.001). A significant positive correlation between the presence of MetS and the IS was observed. MetS patients presented lower uroflowmetric parameters as compared with those without MetS (Maximum flow rate (Qmax): 8.6 vs 10.1, P=0.008 and average flow rate (Qave): 4.6 vs 5.3, P=0.033, respectively), and higher obstructive urinary symptoms score (P=0.064). A positive correlation among both IS–GD and IPSS Score was also observed (adjusted r=0.172, P=0.008 and adjusted r=0.128, P=0.050). MetS is associated with prostate volume, prostatic AP diameter and intraprostatic IS. The significantly positive association between MetS and prostatic AP diameter could support the observation that MetS patients presented lower uroflowmetric parameters. In conclusion, MetS can be regarded as a new determinant of prostate inflammation and BPH progression.

Metabolic syndrome and lower urinary tract symptoms: the role of inflammation.

Hyperinsulinemia and dyslipidemia in non-diabetic benign prostatic hyperplasia

Background. We evaluated the effect of student-dominated small group discussion followed by faculty-moderated presentation as a revision exercise after completion of a teaching module in biochemistry. We assessed the understanding of graduate medical students on the topic and the gain in retention of information, if any, after 15 days. Methods. Small group discussions involving 11–12 students in each group were conducted on 12 application-oriented problems in ‘amino acid metabolism’. A group leader among the students helped to conduct the discussions. While twothirds of the problems were taken up after the discussion during faculty- or student-moderated interactive presentations, the remaining were not. The effects on low-, medium- and high achievers were evaluated by a pre-test and post-test with multiple choice questions immediately after the session. A subjective feedback was also obtained. To test short term memory, a post-test with the same multiple choice questions was conducted after 15 days. Results. The exercise was effective and equally beneficial for low-, medium- and high achievers. The gain was maximum when faculty moderated the presentation session. The students’ retention of their gain after 15 days was complete. All the students wanted more such sessions in future. Conclusion. Student-dominated small group discussion followed by a faculty-moderated presentation is an effective, revision exercise for undergraduate medical students.

Small group discussion followed by presentation as a revision exercise at the end of a teaching module in biochemistry.

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Hyperinsulinemia and dyslipidemia in non-diabetic benign prostatic hyperplasia

Small group discussion followed by presentation as a revision exercise at the end of a teaching module in biochemistry.