Saturday, September 2, 2017

The Effect of Testosterone With / Without Training on Size, Morphology, Neuronal Wiring of Elderly Muscle (Rat Model)

How do youthful+ (probably slightly above range) levels of testosterone affect muscle size, strength, and morphology as we age? That's more or less what the authors of a recent study wanted to know when they injected aging rats with testosterone propionate and observed if/how this would affect aging in the presence or absence of resistance training.
Yes, I know, this is only a rodent study, and no one can tell for sure if similar effects will be observed in human beings... I know. What you can be sure about, however, is that an identical study is not going to be conducted with human subjects. So, all smartasses who don't give a damn about rodent studies and are unwilling to or unable to take them for what they are - basic physiological studies for hypothesis formation - please stop reading here.

Since you have not stopped reading, yet, I guess you will be interested in what the researchers from the São Judas Tadeu University and the São Paulo State University did to analyze the effects of resistance training associated with and without the concomitant the administration of exogenous significant amounts of testosterone.
Read more about studies involving TRT/HRT & co on

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For their study, the scientists used 30 Wistar male rats (Rattus norvegicus). With an initial age of 20 months and a study duration of 4 months, the scientists observed their hairy subjects over a period that's roughly equivalent 11.5 years in human terms (Sengupta 2013). If the results of the study are representative of what we would see in human beings, it would thus be representative of roughly 57-60-year-old human beings. The rats were divided into five groups  ...
  • SEI - 20 months-old that were used as initial control (n = 6);
  • SEF - 24 months-old which remained as final control of the procedures (n = 6);
  • T - 20 months-old which received injections of testosterone propionate (n = 6);
  • S – 20 months-old which underwent resistance training (n = 6) and
  • ST - 20 months-old which were trained and received testosterone injections (n = 6).
The resistance training that was done thrice a week consisted, as it is common practice in rodent studies, of 6-8 'sets' of climbing a ladder with an inter-set rest of 2 minutes, a progressively increased weight on their backs (initial load 50% body weight).
The study used a dosages that are probably slightly higher than the equivalent of what you'd see in the average human TRT -- With respect to the previously voiced concerns about how representative the data from this rodent study would be for humans, it's important to note that the scientists chose a dosage that has previously been shown to (a) increase bone mineral density and growth hormone and (b) trigger significant increases in muscular hypertrophy in aged rats. This means that (a) it is certainly not representative of a classic testosterone cycle in bodybuilders, where the dosing will probably be significantly higher. On the other hand, the levels may be slightly higher than in conservative TRT, where T is often boosted only to "age-appropriate" (whatever that may be), not high(er) youthful levels.
The testosterone was administered in form of 200 mg/20 ml of testosterone propionate (TP), which was administered by intraperitoneal injection, twice a week (Tuesdays and Fridays), starting from the first day of the experiment in the T and ST groups. All rats were euthanized at the end of the study period, soleus and plantaris muscles were removed and prepared for histochemistry and cytofluorescence.
Figure 1: Final body weight (g) and relative muscle mass (as % of total mass) after 4 months (Krause Neto 2017).
As you can see in Figure 1 all three treatments, i.e. testosterone alone (T), training alone (S) and testosterone + training (ST), led to significant increases in the relative soleus and plantaris mass of the rodents - statistically significant were these benefits yet only for the plantaris muscle (note: unfortunately, the total lean and fat mass/body composition of the rodents was not assessed / the relative muscle mass, i.e. indiv. muscle/total mass in Figure 1, right is thus the best proxy we have).
Figure 2: Cross sectional area of type I, II-a & IIx fibers (µm²) of the soleus muscles (Kause Neto 2017); a indicates a significant difference in relation to SEI, b indicates a significant difference in relation to SEF.
For the soleus muscle, significant changes in the cross-sectional area were observed only for the type I fibers in the T, S, and ST group and the type I + type IIA fibers in the ST group.

Training alone makes rodents strong(est)

While the rodents in all three intervention groups got stronger over the 4-months study, it was not the training + testosterone (ST) group that got the strongest. Rather than that, the training only (S) group saw the greatest increases in muscle strength (+81% vs. 43% in T and 66% in ST groups).
In contrast to the maximal strength, though, the absolute training weights showed no significant inter-group difference for the T (training only) and ST (steroids + training) group, yet. With 154.3 g and 147.1 g in the S and ST group respectively, there is, however, a visible "training only" advantage.
Neither resistance training nor testosterone alone or in combination prevented the deterioration of the wiring between brain and muscle: The neuromuscular junction (NMJ) is the link between the brain and your muscles. It's deterioration and the subsequent denervation of muscle fibers often precedes (if not triggers) the onset of muscle loss. Accordingly, the absence of changes in the corresponding parameters assessed in the study at hand is a problem, because a severe degeneration of the NMJ may trigger problems you'd otherwise associate with sarcopenia, i.e. the loss of skeletal muscle mass and strength as a result of aging. This result is in line with previous resistance training studies (Deschenes 2015), but in contrast to studies which used an endurance training protocol that kept the NMJs functional (Deschenes 2016).
Hormone/Testosterone replacement therapy is one of the top-sellers in so-called/self-proclaimed anti-aging clinics. Now, the study at hand has been conducted in rodents, not men, but with its design, it is still representative of the average healthy, non-hypogonadal, but aging man who's fed up of progressive muscle and strength loss. The same guy who would pay the aforementioned clinics a visit to get testosterone shots that will up his levels to the upper end of the normal range of men in their twenties.

Steroids alone will reverse the age-related decline in muscle strength and size

If we assume for the time being, that the results Krause Neto et al. observed in this model of aging translate (not necessarily 1:1, but at least as far as the general results are concerned) to human beings, our guy from the previously described example will see results - after all, significant increases in muscle strength and size (esp. in fast-twitch muscles you'd use to lift or sprint, those muscles that deteriorate most as you age and thus affect the jacked look you may have had in your 20-40s) were observed in all three treatment groups.

Before you run to the next best HRT clinic, though, I suggest you take a look at the effects of training alone. With strength and size increases that were similar to the ones the scientists observed in the steroid (T) and steroid + training (ST) groups, the study at hand clearly confirms the potent anti-(muscle-)aging effects of a simplistic strength training (weight carrying) protocol.

Body composition probably benefits most from adding testosterone to training

A non-deniable downside to training with suboptimal testosterone levels, however, is the reduced effect on body composition. Even though the scientists didn't measure the body fat of their hairy subjects directly, the reduced reduction in body weight (-14-15% w/ testosterone vs. -10% w/ training only) clearly suggests that the rodents on "T" lost more body fat than their peers in the training-only group.
Figure 2: Relative change in lean and fat mass in response to changes in serum testosterone (calculated based on Bhasin. 2001) - you can read up on the different effect size of T on fat and muscle in my previous article "Quantifying the Big T".
And that's a result that should not surprise you if you've read my detailed elaborations on the effects of testosterone on muscle size in the "Intermittent Thoughts on Building Muscle" (go to the article overview and conclusion or read up on the different effect size of low/high testosterone on body fat and skeletal muscle in the corresponding part of the article series: "Quantifying the Big T"), in which I showcase that the effect of low testosterone on body fat is much more pronounced than its effects on skeletal muscle size.
You don't need TRT to counter the age-related loss of muscle strength and size: Yes, the effect on the rodents body composition seems to be more pronounced with youthful (or even higher) testosterone levels. Before jumping to the conclusion that you cannot get along without HRT/TRT as you age, though, there are yet three things you shouldn't forget:
  • Learn more about the effects of TRT on body comp (if T is low), here
    First, the strength-decline that's probably the greatest obstacle to normal physiological function in the elderly was countered at least as, if not more effectively, by training alone.  
  • Second, even if the body fat loss was probably lower for the T than for the S and ST group, the muscle-to-total-body-weight ratio leaves little doubt that the training only (T) group saw improvements in body composition, too. 
  • Third, a more elaborate workout that isn't limited to carrying weight upstairs for 6-8 sets may have significantly more pronounced effects on older men's body composition, would thus reduce the testosterone advantage in terms of body composition, and could, on top of that, augment the training-induced changes in muscle size and strength even further - regardless of whether you are or aren't on TRT.
So, overall, there's little doubt: the study clearly confirms the potential benefits of HRT/TRT as an anti-aging program for aging muscles, guys. It does, however, and I believe that's at least as important, also demonstrate that a little training will also go a long way - at least, if your testosterone levels suffered only the natural decline and are not rock bottom, to begin with. | Comment!
  • Bhasin, Shalender, et al. "Testosterone dose-response relationships in healthy young men." American Journal of Physiology-Endocrinology And Metabolism 281.6 (2001): E1172-E1181.
  • Deschenes, Michael R., et al. "Effects of resistance training on neuromuscular junction morphology." Muscle & nerve 23.10 (2000): 1576-1581.
  • Deschenes, Michael R., et al. "Effect of resistance training on neuromuscular junctions of young and aged muscles featuring different recruitment patterns." Journal of neuroscience research 93.3 (2015): 504-513.
  • Deschenes, Michael R., et al. "Effects of exercise training on neuromuscular junction morphology and pre-to post-synaptic coupling in young and aged rats." Neuroscience 316 (2016): 167-177.
  • Krause Neto, Walter et al. "Divergent effects of resistance training and anabolic steroid on the postsynaptic region of different skeletal muscles of aged rats." Experimental Gerontology 98 (2017): 80-90.
  • Sengupta, Pallav. "The laboratory rat: relating its age with human's." International journal of preventive medicine 4.6 (2013): 624.