The latter is suggested to occur through increased expression of Pax7 and MyoD transcription factors (Thomas et al., 2010; Sambasivan et al., 2011) which induce satellite cell expansion, differentiation, and self-renewal of muscle function and mass (Kitajima and Ono, 2016; Chidi-Ogbolu and Baar, 2019). In addition, estrogen is also known to activate insulin/IGF-1 (Lee et al., 2004) and PI3K/Akt (Mangan et al., 2014) pathways, potentially enhancing the mechanisms regulating MPS (Hansen et al., 2012) and consequently muscle growth (Smith et al., 2014). While less studied in this sphere, endogenous oestrogens seem to have a metabolic role in regulating skeletal muscle; for instance, being critical for the regrowth of atrophied skeletal muscle (Sitnick et al., 2006)- an action mediated by the estrogen receptors, located within skeletal muscle tissue that function as transcription factors (Hansen and Kjaer, 2014). Oestrogens are steroid hormones, primarily produced in the ovaries from testosterone via an aromatase enzyme, of which women have four times the amount compared with men, until the menopause (Hansen and Kjaer, 2014). However, transient activation of ERK1/2 induced by testosterone was not found to be directly related to the hypertrophic signaling cascade; though activated ERK can phosphorylate co-activators of the intracellular receptor at the nuclear level (Bratton et al., 2012), through potentiation of estrogen receptor activation function 1 (AF-1) by Src/JNK (serine 118-Independent pathway) which promotes cellular growth (Feng et al., 2001; Estrada et al., 2003).
An important observation in the SNB is that normal aging in rodents leads to a decline in testosterone and AR expression on the motor neurons (Matsumoto and Prins, 1998), likely underlying in the shift towards decreased motor neuron soma size within the nucleus from 9 to 22 months of age (Fargo et al., 2007) and the decrease in sexual behavior with age (Larsson, 1958). Separate studies have also indicated age-related functional declines in the human motor system at the levels of the cortex, spinal cord, and motor neurons (Wagman and Lesse, 1952, Kido et al., 2004, McGinley et al., 2010, Kaya et al., 2013, Yao et al., 2014). Although not heavily examined in humans, we review the few studies in the human literature that have examined the role of anabolic hormones on the motoric system. While these studies do not directly indicate that changes in anabolic hormones contribute to reduced human performance in the elderly (e.g., muscle weakness and physical limitations), they do suggest that additional research is warranted along these lines. Short-term fasting (16-24 hours) increases growth hormone secretion dramatically — GH can spike 2-5x during a fast. Eccentric-emphasized training (slow negatives) causes more muscle damage and correspondingly higher local IGF-1 expression during the repair process.
That’s not a subtle effect — that’s a quarter of your growth factor capacity eliminated by poor sleep habits. Research from the University of Chicago demonstrated that restricting sleep to 4 hours per night for just one week reduced IGF-1 levels by a staggering 24%. Growth hormone is released in pulsatile fashion during deep sleep, with the largest spike occurring in the first 90 minutes after falling asleep. You can have solid testosterone levels and still underperform if your IGF-1 is in the gutter. Over a decade of coaching clients on hormone optimization, I’ve found that most people obsess over their testosterone numbers while completely ignoring IGF-1. Some clients with modest testosterone increases report dramatic subjective improvements. This IGF-1 reduction is one reason some natty plus practitioners combine enclomiphene with MK-677, a growth hormone secretagogue that raises IGF-1.
A study in the Journal of Sports Science and Medicine found that bovine colostrum supplementation increased serum IGF-1 in athletes over an 8-week period. Vitamin D acts as a hormone that modulates GH sensitivity in the liver — low vitamin D means less IGF-1 per unit of growth hormone released. Heavy compound movements (squats, deadlifts, presses) generate the largest systemic IGF-1 response due to the sheer volume of muscle tissue recruited.
However, a study using a validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for measuring T reported T levels were 1.8 times higher in pre-menopausal women with an average age of 35 years compared to post menopausal women with an average age of 59 years (Rothman et al., 2011). Additionally, endogenous testosterone release pulses are lower in frequency and amplitude at night in middle-aged men compared to young men (Luboshitzky et al., 2003). With advancing age in men, free and total testosterone begin to decrease between the third to fifth decade of life, and this decline continues progressively thereafter (Harman et al., 2001). In addition to possible influences on muscle tissue, recent evidence has emerged indicating that circulating factors also have a profound influence on the nervous system, as Villeda et al. observed improved cognitive function in old mice injected with serum from young mice, while Ruckh et al. observed remyelination is enhanced in older mice via parabiosis with young mice (Ruckh et al., 2012, Villeda et al., 2014).