How do muscles actually grow — and what really matters for hypertrophy?

In this episode, I break down muscle growth from the ground up, starting with muscle structure and working all the way through the practical training variables that actually drive hypertrophy.

We cover how muscle fibers are built, why muscle cells are uniquely multi-nucleated, and how satellite cells and myonuclei influence growth potential and long-term adaptations (including the concept of “muscle memory”). From there, we dig into how resistance training shifts net protein balance, why muscle protein synthesis and breakdown both rise with training, and why hypertrophy is often delayed when people first start lifting.

A major focus of this episode is mechanotransduction — how mechanical loading from resistance training is converted into chemical signals that stimulate muscle growth. We unpack what we know (and don’t know) about mTOR signaling, phosphatidic acid, kinase pathways, and why mechanical tension is the primary driver of hypertrophy.

From there, the episode gets highly practical. We break down:

• Why proximity to failure matters more than load

• How volume really works (and why “dose-dependent” doesn’t mean linear)

• The role of training frequency and how to distribute volume

• Why stretch and lengthened positions matter for growth

• Load and rep ranges for hypertrophy vs strength

• Exercise selection, machines vs free weights, and compound vs isolation lifts

• Rep tempo, intensity techniques, and what doesn’t meaningfully affect growth

• Why systemic hormone spikes from training don’t predict hypertrophy

I close with clear, evidence-based takeaways you can actually apply: how hard to train, how much volume most people need, when failure makes sense, how to structure exercises, and how to prioritize effort, recovery, and adherence over gimmicks.

If you want a science-based framework for building muscle — without myths, hype, or unnecessary complexity — this episode lays it out step by step.

SPONSORS

• Workout Builder – Customized training programs for all experience levels: https://biolayne.com/workout-builder

• Team Biolayne – One-On-One Coaching: https://biolayne.com/online-coaching

LAYNE'S COMPANIES

Carbon Diet Coach: https://joincarbon.com/podcast

Outwork Nutrition: https://outworknutrition.com

REPS Research Review: https://biolayne.com/reps

Workout Builder: https://biolayne.com/workout-builder

Team Biolayne: https://biolayne.com/online-coaching

Physique Coaching Academy: https://physiquecoachingacademy.com

FOLLOW LAYNE

http://www.facebook.com/laynenorton

http://www.twitter.com/biolayne

http://www.instagram.com/biolayne

TIMESTAMPS

0:00:00 - Intro

0:04:53 - Muscle Function

0:06:23 - Muscle...

In this Building Muscle Masterclass, I sit down with Dr. Stu Phillips — the world’s most cited researcher in exercise science and protein metabolism. If you care about building muscle, eating enough protein, lifting smarter, or cutting through the noise in the fitness world, this is a must-listen.

Stu and I go deep on the biggest questions in hypertrophy and nutrition, backed by some of the most important studies in the field:

• What actually drives muscle growth and what most people still get wrong

• How much protein you should really eat to maximize hypertrophy (and what the meta-analyses say)

• Whether high-protein diets harm your kidneys (spoiler: nope)

• Plant vs. animal protein: does the source matter, or is it all about leucine?

• Do hormone spikes from training matter for gains?

• Should women change their programming based on menstrual cycle phase?

• The truth about “lifting heavy” — do you need it for hypertrophy?

And MORE

If you want the clearest, most up-to-date breakdown of protein science and muscle growth from the guy who literally did the research I base many of my recommendations on… this is your episode.

SPONSORS

• Carbon Diet Coach – 14 day free trial: https://joincarbon.com/podcast

• Workout Builder – Customized training programs for all experience levels: https://biolayne.com/workout-builder

LAYNE'S COMPANIES

Carbon Diet Coach: https://joincarbon.com/podcast

Outwork Nutrition: https://outworknutrition.com

REPS Research Review: https://biolayne.com/reps

Workout Builder: https://biolayne.com/workout-builder

Team Biolayne: https://biolayne.com/online-coaching

Physique Coaching Academy: https://physiquecoachingacademy.com

FOLLOW LAYNE

http://www.facebook.com/laynenorton

http://www.twitter.com/biolayne

http://www.instagram.com/biolayne

FOLLOW STU

https://www.instagram.com/mackinprof

http://www.twitter.com/mackinprof

TIMESTAMPS

0:00:00 - Intro

0:01:50 - Background

0:08:33 - Biochemistry First

0:12:02 - Student Experience

0:14:53 - Single Most Important Thing for Muscle Growth

0:16:04 - Mechanisms of Hypertrophy

0:19:48 - Consistency is Key

0:21:46 - Muscle Growth and Hormones

0:28:34 - Acute vs Chronic

0:32:42 - Cortisol

0:36:19 - Carbon Diet Coach

0:37:19 - Muscle, Hormones, and Training for Women

0:49:56 - Training Auto-Regulation

0:55:42 - How Much Protein

1:08:06 - Workout Builder

1:09:02 - Protein and Kidneys

1:26:20 - Muscle and Metabolic Health

1:30:05 -...

In this week’s Q&A episode, I dig into your most common questions — from supplements to training to nutrition — and break them down with actual data, not influencer mythology. If you’ve ever wondered whether collagen is worth the hype, if fiber does more than “help you poop,” or whether turkesterone is anything more than TikTok creatine-with-a-fedora… this episode is for you.

We cover:

• Collagen:

Does it help joints? Skin? Connective tissue? Muscle? I walk through the clinical trials (including the ones influencers never mention) and explain where collagen actually works… and where it absolutely doesn’t.

• Fiber:

Yes, it helps your gut — but that’s just the start. We look at the research on mortality risk, insulin resistance, weight loss, inflammation, CKD, energy balance, colon cancer, and why higher fiber intake consistently predicts better health across multiple systems.

• Turkesterone & Ecdysteroids:

The internet loves calling this “natural anavar.” The human data… does not. I break down the preliminary studies, the animal research, and what’s real versus what’s marketing.

• Burnout & Training Balance:

How I manage training, work, and life without flaming out — and what actually matters for long-term consistency.

• Protein Needs After 40:

Do you need more protein as you age? What does the research say about anabolic resistance, amino acid signaling, and muscle protein synthesis in older lifters?

• Things That Hurt Muscle Growth:

Ice baths, alcohol, smoking, NSAIDs, corticosteroids — we go through the actual evidence on what blunts hypertrophy, what doesn’t, and what matters in the real world.

• Sugar & Weight Gain:

Do non-diabetics need to “fear” sugar? Or does it really come down to calories? We dig into metabolic ward studies, DIETFITS, high-sucrose diets, and the boring reality that calorie balance still wins.

• Men vs. Women in Training & Nutrition:

Sex differences in hypertrophy, strength gains, metabolic rate, and menstrual cycle effects on performance — what’s real and what’s bro-science?

• Training Over 50:

How many sets do you actually need to build muscle after 50? We review the dose-response data, multi-set vs single-set research, and the RCTs showing older adults can grow — there are no “non-responders.”

All research is cited directly from the studies mentioned — RCTs, meta-analyses, mechanistic papers, and long-term cohorts.

If you want evidence without the nonsense, this is your episode.

*SPONSORS*

• Workout Builder – Customized training programs for all experience levels: https://biolayne.com/workout-builder

• Physique Coaching Academy - Advanced Coaching and Nutrition Education for Personal Trainers: https://physiquecoachingacademy.com

LAYNE'S COMPANIES

Carbon Diet Coach: https://joincarbon.com/podcast

Outwork Nutrition: https://outworknutrition.com

REPS Research Review: https://biolayne.com/reps

Workout Builder: https://biolayne.com/workout-builder

Team Biolayne: https://biolayne.com/online-coaching

Physique Coaching Academy: