Aging related erectile dysfunction—potential mechanism to halt or delay its onset

Abstract

Erectile dysfunction (ED) will visit every man at some time in his life. The age at when that knock on the door is heard is totally dependent on one’s genetics as well as other extrinsic factors. Unlike guests who come for a visit and then leave, once ED shows up it tends to hang around forever. To add insult to injury, the longer ED hangs around, the worse it will get. It is estimated that by the time a man is in his 40’s, he has about a 40% chance of having some form of ED and this prevalence increases about 10% per decade thereafter. This suggests that the aging related process that leads to ED begins early in life. It turns out that the most common cause of ED, regardless of the patient’s age, is due to a problem with the vascular system of the penis. However, this specific aging related vascular problem is not caused by arterial disease but due to a dysfunction and/or loss of the corporal smooth muscle cells (SMC), the main constituent of the corporal sinusoids. As one gets older, these SMC continue to degrade and disappear. When approximately 15% of these cells have been impacted, it results in an inability of the corporal tissue to retain and/or prevent the blood from “leaking” out of the corporal sinusoids into the systemic veins. However, the corporal SMC themselves begin to combat this aging process by expressing the inducible nitric oxide synthase (iNOS) enzyme to make nitric oxide (NO) in an attempt to quench the high intracellular oxidative stress responsible for the SMC apoptosis. When this iNOS pathway is then pharmacologically upregulated, reversal of these aging related changes in the corpora with correction of the venous leakage is observed. Since we believe that aging related ED is pathologically the same disorder as essential hypertension, the development of a therapeutic regimen that can halt, delay or possibly reverse the cellular processes that lead to aging related ED should also be applicable to those patients diagnosed with essential hypertension.

Human tissue kallikrein 1 ameliorates erectile function via modulation of macroautophagy in aged transgenic rats

“…However, as men age, an aging-dependent decrease in function occurs in the cavernous smooth muscle. Decreased levels of testosterone, oxidative stress, fibrosis, and apoptosis of cavernous smooth muscle are also major causes of age-related ED (Bivalacqua et al, 2003;Ferrini et al, 2017).…”

“…Representative ICP tracings were measured using stimulations at 2.5 V and 5 V (A) for 1 min each. Decreased levels of testosterone, oxidative stress, fibrosis, and apoptosis of cavernous smooth muscle are also major causes of age-related ED (Bivalacqua et al, 2003;Ferrini et al, 2017). Data are expressed as mean AE SD (n = 10 rats per group).…”

The Effects of Calorie Restriction and Exercise on Age-Related Alterations in Corpus Cavernosum

“…The development of a penile erection can simply be summarized in two sequential steps: (1) the transportation of blood into the cavernosal sinusoids resulting in the enlargement and rigidity of the penis, and (2) the reduction of venous outflow via veno-occlusion to maintain the enlargement and rigidity of the penis (Ferrini et al, 2017). However, this twostep process depends on a complex balance and coordination of neurogenic, vascular, and humoral events (Jang et al, 2017), such as the parasympathetic, sympathetic, and nitrergic nerves, neurotransmitters, blood vessels, and cavernous muscles (Claudino et al, 2004).…”

A systematic review on cell‐seeded tissue engineering of penile corpora

“…Erectile dysfunction (ED) of somatic origin is a frequently occurring disease of the CC (Ferrini, Gonzalez‐Cadavid, & Rajfer, ). Present therapies include oral PDE‐5 inhibitor or intracavernosal injection of smooth muscle relaxant and α‐adrenoreceptor antagonists; however, the effectiveness is around 70% but lower in subgroups (after radical prostatectomy or with comorbidities such as diabetes mellitus) (Park, Kim, & Park, ; Porst, ).…”

“…Erectile dysfunction (ED) of somatic origin is a frequently occurring disease of the CC (Ferrini, Gonzalez-Cadavid, & Rajfer, 2017).…”