Is there any studies showing that females have generally less mTOR activity than males?
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I have never seen any studies related to mTOR and gender.
It seems you might be suggesting something like a difference in mTOR activity might explain lifespan differences between the sexes.
I have never heard of a theory like this, but obviously not impossible.
Thanks for your answer! After digging a lot I found this study which shows for the first time on an experimental level that there is likely a difference. Why the difference really exists and how it impacts aging is still questions we don’t fully understand yet and can answer. Here are some quotes from the study.
“Our study demonstrated that both tissue p-AKT and pS6 were higher in young males than young females and were associated with increased body weight and insulin. These data can explain larger body size and faster aging in males.”
“Since phosphorylation of S6 was inhibited by rapamycin, we consider it as the most reliable marker of mTORC1 activity, which is rapamycin sensitive. Here we assessed the activity of the mTOR pathway by pS6 (a marker of mTORC1) and p-AKT (Ser 473), which is a rapamycin-insensitive marker of mTORC2. At age of 6 months, males were significantly heavier than females. Both pS6 and p-AKT were statistically higher in at least some male organs, as indicated by both immunoblotting and immunohistochemistry (Fig. (Fig.22 and and3).3). Levels of pS6 significantly correlated with body weight and p-AKT (Fig. (Fig.22 and and3).3). Male mice had significantly higher fasted insulin levels and higher insulin response to re-feeding when compared to females … In conclusion, our study demonstrated that both p-AKT and pS6 were higher in young males than in young females. These data can explain robust growth and faster aging in male species.”
“Instead, aging is driven by the mTOR pathway, which is activated by growth factors, nutrients (food), insulin (which is induced by nutrients), testosterone and some other factors that all stimulate cellular and organismal growth. When development is completed the same still active mTOR pathway then drives aging and age-related diseases [189]. In other words, aging is a quasi-program of development, an aimless continuation of growth driven by nutrient/insulin-sensing signaling pathways [60]. Therefore, males live shorter not because they are too weak but because they are too robust (due to hyperactive mTOR).”
“Our work complements outstanding discoveries by Bartke and co-workers that high levels of growth hormone shorten life span. In fact, high levels of growth hormone (GH), IGF-1, insulin all decrease lifespan in mice. Such mice are big and short-lived. In contrast, mice deficient in GH/IGF-1 signaling live longer [190-198]. The GH/IGF-1 axis activates the mTOR pathway. In line with the hyperfunction theory is an excellent observation that big mice die young: early life body weight predicts longevity in genetically heterogeneous mice [199]. Our data provide mechanistic explanation: the higher the TOR activity, the bigger the mice. Early life growth hormone treatment shortens longevity [200, 201] and instead antagonists of these hormones may extend life span, treat cancer and some age-related diseases [202-206].”
“The hyperfunction theory suggests that if aggressive males must have high mTOR activity early in life, they must age fast too. Furthermore, the theory suggests that these aging-promoting genes like mTOR are antagonistically pleiotropic [110]. Active and robust mTOR pathway provides advantage early in life including reproduction (noteworthy, mTOR increases spermatogenesis and fertility). At the same time mTOR decreases survival much later in life, when an organism would not exist in dangerous for males natural environment anyway. And this mechanism is much more important to males than to females. It was theoretically described why and how males must age faster and die younger than females [12]. However, for the first time this hypothesis was supported experimentally.”
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Here is another one where Blagosklonny describes his view
“In males, muscle hypertrophy and heavy body helps to compete with other males. (In fact, men are larger than women.) Cellular growth and hypertrophy are stimulated by the mTOR (mammalian Target of Rapamycin) intracellular signaling pathway. Insulin, growth factors, amino acids, glucose lipoproteins, and testosterone all activate the mTOR pathway [6-9]. In turn, the mTOR pathway stimulates protein synthesis and cell size growth [10]. For example, skeletal muscle hypertrophy depends on the mTOR pathway [11,12]. In addition, inhibition of the mTOR pathway decreases testosterone levels and spermatogenesis [13]. Thus, activation of mTOR may provide a selective advantage to young males. … Thus, over-activation of mTOR may provide an advantage (muscle hypertrophy, high levels of testosterone and high spermatogenesis) in early life at the cost of accelerated aging later in life. As an illuminating example, mice over-expressing growth hormone exhibit increased levels of IGF-I and adult body size, reduced life span and reproductive life span [26]”
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