It may be worthwhile to train with periods of lightweight, high reps, and training periods with heavier weight to elicit changes in different genes related to muscle growth. The largely similar changes in DNA response also may explain how heavy vs. and light weight training contribute to equal gains in muscle growth when the volume is similar.


  • Low Weight, high-rep workout plan consisting of 30% of a 1-RM resulted in largely similar muscle DNA responses as high weight, low-rep workout plan.
  • There were subtle differences in the DNA responses to the heavy and light weight training, which suggests a combination of both may be beneficial for optimal muscle growth.


Muscle growth is a series of anabolic and catabolic steps in which the anabolic state exceeds the catabolic state. Over the last few years, it has been firmly established that both heavy and lightweight, when taken to failure, can equally build muscle when performed to failure. However, for strength increases, heavier weight must be used.

How do alterations in genes for muscle protein synthesis contribute to an anabolic state? Well, these genetic changes play a pivotal role in promoting muscle hypertrophy during strength training. Historically, there was a prevailing belief that lifting light weights with a high number of reps primarily fostered aerobic adaptations in muscle, leaving minimal room for anabolic processes to enhance muscle mass. Contrary to this earlier assumption, contemporary research has shed light on the matter. We’ve come to realize that this previous notion is entirely false. Interestingly, irrespective of the weight used, similar anabolic processes can be triggered in the muscle when one trains to muscular failure


What is unclear is the DNA molecular response of different anabolic pathways in response to muscular endurance training (>20 reps) and lifting heavy weights (<10 reps). Higher-intensity exercise that results in increased metabolic stress has been suggested to result in different DNA responses. For example, high-intensity sprints that included a change of direction resulted in different DNA molecular adaptations in muscle than running in a strength line. (Maasar et al., 2021)  Also, HIIT training has been found to result in increased DNA mitochondrial content in the muscle compared to steady-state training. (Torma et al., 2019)

A 2010 study comparing low-weight, high-reps vs. high-weight, low-reps found greater protein synthesis 24 hours following high-rep training. (Burd et al., 2010) One limitation of this study was that the high rep/lightweight group performed more volume (i.e., sets x reps), which could have favored a greater anabolic response because the lightweight group performed more reps per set.


A 2019 study found that subjects training with light weight/high rep (30% of a 1-RM) workouts resulted in greater aerobic adaptations in muscle than heavy weight/ low rep (80% of a 1-RM). Interestingly, both groups had similar increases in strength, hypertrophy, and satellite cell numbers. (LIM et al., 2019)

Other scientists have found that high-volume exercise (32 sets) results in greater sarcoplasmic hypertrophy (i.e., expansion of fluid volume in the muscle without changes in the muscle size). (Haun et al., 2019) Based on these studies, greater anabolic signaling pathways may exist with lighter weight/high rep training.

Researchers did a study to look at DNA responses for genes involved in muscle growth. One group of subjects performed light-weight, higher reps (i.e., 30% of a 1-RM) and then returned and did a heavy-weight, low-rep workout. The exercise consisted of a back squat workout and leg extensions.  The researchers were clear to ensure that the volume was similar between the groups.

The researchers found that the high-rep, light weight resulted in different DNA regions than the heavyweight group, but the responses were largely similar.  The study findings are similar to the different molecular responses to change of direction of direction running to running straight forward. (Maasar et al., 2021)

high reps vs low reps anabolic state low weight high reps vs high weight low reps strength training vs bodybuilding low weight high rep workout plan back squat workout heavy vs light weights
This suggests that it may be worthwhile to train with periods of lightweight, high reps, and training periods with heavier weight to elicit changes in different genes related to muscle growth.


The author stated, “Training at 30% of a 1-RM to failure and training at 80% until failure resistance exercise bouts produced unique DNA methylation responses across various gene promoters, albeit largely similar transcriptomic responses. (Sexton et al., 2023) These data continue to add insightful information to the body of literature comparing the muscle-molecular responses of higher load versus lower load resistance training paradigms.”

This suggests that it may be worthwhile to train with periods of lightweight, high reps, and training periods with heavier weight to elicit changes in different genes related to muscle growth. The observation of comparable alterations in DNA response sheds light on an intriguing phenomenon. It provides a plausible explanation for how both heavy and light weight training can lead to similar gains in muscle growth, especially when the training volume remains consistent


Burd, N. A., West, D. W., Staples, A. W., Atherton, P. J., Baker, J. M., Moore, D. R., Holwerda, A. M., Parise, G., Rennie, M. J., Baker, S. K., & Phillips, S. M. (2010). Low-load high volume resistance exercise stimulates muscle protein synthesis more than high-load low volume resistance exercise in young men. PLoS One, 5(8), e12033.

Haun, C. T., Vann, C. G., Osburn, S. C., Mumford, P. W., Roberson, P. A., Romero, M. A., Fox, C. D., Johnson, C. A., Parry, H. A., Kavazis, A. N., Moon, J. R., Badisa, V. L. D., Mwashote, B. M., Ibeanusi, V., Young, K. C., & Roberts, M. D. (2019). Muscle fiber hypertrophy in response to 6 weeks of high-volume resistance training in trained young men is largely attributed to sarcoplasmic hypertrophy. PLoS One, 14(6), e0215267.

LIM, C., KIM, H. J., MORTON, R. W., HARRIS, R., PHILLIPS, S. M., JEONG, T. S., & KIM, C. K. (2019). Resistance Exercise–induced Changes in Muscle Phenotype Are Load Dependent. Medicine & Science in Sports & Exercise, 51(12), 2578-2585.

Maasar, M.-F., Turner, D. C., Gorski, P. P., Seaborne, R. A., Strauss, J. A., Shepherd, S. O., Cocks, M., Pillon, N. J., Zierath, J. R., Hulton, A. T., Drust, B., & Sharples, A. P. (2021). The Comparative Methylome and Transcriptome After Change of Direction Compared to Straight Line Running Exercise in Human Skeletal Muscle [Original Research]. Frontiers in Physiology, 12.


Sexton, C. L., Godwin, J. S., McIntosh, M. C., Ruple, B. A., Osburn, S. C., Hollingsworth, B. R., Kontos, N. J., Agostinelli, P. J., Kavazis, A. N., Ziegenfuss, T. N., Lopez, H. L., Smith, R., Young, K. C., Dwaraka, V. B., Frugé, A. D., Mobley, C. B., Sharples, A. P., & Roberts, M. D. (2023). Skeletal Muscle DNA Methylation and mRNA Responses to a Bout of Higher versus Lower Load Resistance Exercise in Previously Trained Men. Cells, 12(2).

Torma, F., Gombos, Z., Jokai, M., Takeda, M., Mimura, T., & Radak, Z. (2019). High intensity interval training and molecular adaptive response of skeletal muscle. Sports Medicine and Health Science, 1(1), 24-32.

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