Diminished Estradiol Explains Faster Muscle Loss Following Menopause

Both genders lose muscle mass and strength with age, leading to sarcopenia and frailty. Why do women undergo age-related muscle loss more rapidly following menopause, however? Researchers here suggest that the sex hormone estradiol is necessary to support the activity of muscle stem cells, and thus falling levels of estrogen following menopause is the mechanism driving this outcome. Loss of stem cell function in muscle tissue is also the most credible cause for the onset of sarcopenia without considering gender, so this all fits together quite nicely.

Over the course of an individual's life, skeletal muscle undergoes numerous injurious insults that require repairs in order for function to be maintained. The maintenance and injury repair of skeletal muscle is dependent on its resident stem cell (i.e., the satellite cell). With proliferation, satellite cells undergo asymmetric division through which a subpopulation of the daughter satellite cells do not differentiate, but instead return to quiescence, repopulating the satellite cell pool (i.e., self-renewal). The balance of this asymmetric division process is critical and necessary to ensure the life-long preservation of satellite cells in skeletal muscle.

Aging diminishes the satellite cell pool and, as a result, the regenerative capacity of skeletal muscle in aged males is impaired compared to that of younger males, but such age-induced impairments in females is less studied. Similarly, age-associated changes in the satellite cell environment, in combination with cell-intrinsic alterations, disrupt quiescence and the balance of asymmetric division, ultimately impacting satellite cell maintenance and muscle regenerative potential. Such results support the concept that circulatory factors, including hormones that differ between the young and old systemic environments and the activity of their subsequent signaling pathways, contribute to age-associated decrements in satellite cell maintenance and overall muscle regenerative capacity.

A well-known hormone that changes with age is estradiol, the main circulating sex hormone in adult females. Serum estradiol concentration declines dramatically at the average age of 51 in women, corresponding to the time of menopause. Estradiol deficiency reduces skeletal muscle mass and force generation in women and prevents the recovery of strength following contraction-induced muscle injury and traumatic muscle injury in female mice. However, evidence that this regenerative phenotype involves effects of estradiol directly on satellite cells is lacking.

In this study, we use rigorous and unbiased approaches to demonstrate the in vivo necessity of estradiol to maintain the satellite cell number in females. Further, we use mouse genetics to show that the molecular mechanism of estradiol action is cell-autonomous signaling through estrogen receptor α (ERα). Specifically, we show the functional consequence of estradiol-ERα ablated signaling in satellite cells including impaired self-renewal, engraftment, and muscle regeneration, and the activation of satellite cell mitochondrial caspase-dependent apoptosis. Together, these results demonstrate an important role for estrogen in satellite cell maintenance and muscle regeneration in females.

Link: https://doi.org/10.1016/j.celrep.2019.06.025

Comments

Aside, I have never understood why this and other anti-aging groups are usually 85% male.

Posted by: JohnD at July 19th, 2019 9:09 AM

@JohnD

Men, I believe, have much more to lose as they age. Strength, which has always been known as a male trait. Virility, ego, all diminish to an extent. Just the idea of becoming frail and less of a "man" causes issues to many men. I could be wrong though..

Posted by: Person1234 at July 19th, 2019 11:48 AM

Women spend considerable money on cosmetics, "nip & tuck" cosmetic procedures, botox, and a host of other things to combat "looking old". One would think that women would be the most enthusiastic supporters of stuff like SENS and the like to actually do something real about aging. It is quite the paradox.

One explanation is that idea of life extension is an outgrowth of the nerdly scene of the 1980's where these ideas were first bandied about. This would explain the kryptonite effect on women.

Posted by: Abelard Lindsey at July 19th, 2019 1:54 PM

Both good speculations, I will add a third. Reproductive age lasts 20 years later in life for men then it does for women. Thus women come to terms with earlier , and are more accepting of, their mortality.

Posted by: JohnD at July 19th, 2019 4:19 PM

@JohnD: No we aren't. Women aren't any keener on dying than men and honestly I can't see the link with reproduction other than it being an easy cop out when other explanations aren't forthcoming. But personally I've found this and other fora pretty sexist and prone to stereotyping women, so that could be one reason they refrain from engaging.

Does anyone know the gender ratio at events like Radfest? My hunch is that it isn't 85-15 but I could be wrong.

Posted by: Barbara T. at July 24th, 2019 3:34 PM

@Barbara T

[Off topic]
Stereotypes and generalizations are easy and obvious heuristics. They have their huge weaknesses though. There common memes where guys are considered young and immature at age of 35. Not so much for the girls. On to of that even the guys at FA manage to offend you (and I am asking them). And we probably even infuriate you because we don't even realize why you get offended. But that's the fact to address we don't comprehend. At least not without mental effort

However, the sad truth is that we all age and Desperately need anti-aging therapies. Since the men have shooter health and life span such therapies might benefit men more in relative terms than women. But we don't know that for sure

[/Off topic]

Posted by: Cuberat at July 25th, 2019 8:47 AM

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