Exploring Autophagy: The Science of Cellular Renewal

Author: Izzy Sapien, MSNBL

Last Update: 1/8/26

What Is Autophagy?

Autophagy is one of the most referenced biological processes in anti-aging and  longevity science but what actually is autophagy? 

Though it's coined for its role in acting as a “housekeeper” for damaged cells, which is critical for homeostasis, autophagy is actually so much more than that.¹ The physiological functions of autophagy range from:

• Energy production – Autophagy helps mobilize energy stores, regulating glucose, lipids, and protein breakdown in cells.
  

• Intracellular maintenance – Autophagy contributes to quality control and the replacement of cellular components.
  

• Signaling – Sometimes autophagy can selectively break down certain parts of the cell while leaving others untouched, which is important for cellular regulation.

• Development and differentiation- We know autophagy is related to the process of morphogenesis, which is when cells differentiate into functional tissue during development.¹

Interestingly there are multiple forms of autophagy. Macroautophagy is the most well-studied and  “popular” form because it does the “bulk cleanup”.¹ However, there is an increasing body of research on the role of Golgiphagy, a newly discovered form of autophagy which regulates the golgi apparatus- an organelle crucial to age related decline.¹ 

We also know the autophagic system declines with age, which is extremely detrimental in the brain where it impacts synaptic development, maintenance, and function.¹ 

The key takeaway here is that: evidence supports the role of autophagy as a critical regulator of health from birth through maturity.¹

Autophagy and Mitochondria: Energy and Cleanup

Yes, we all know mitochondria as the “powerhouse of the cell.” But what does that actually mean?

Mitochondria are essentially battery cells - critical for cell homeostasis.¹ As the primary source of ROS (reactive oxygen species) and RNS (reactive nitrogen species), mitochondria can actually induce autophagy.¹ This form of autophagy is called mitophagy.¹ Mitophagy is induced during many stressful conditions such as nutrient deprivation.¹ Interestingly, this process can also self-signal damaged mitochondria to remove themselves.¹ This is very important because damaged and dysfunctional mitochondria are harmful to the body.

Can You Support Autophagy?

Over the past 20 years, the science of cellular health has explored ways humans can support autophagy through a variety of methods in the hopes of prolonging lifespan or healthspan. Various evidence has shown promising results in the following areas:

1. Autophagy & Caloric Restriction - Though the mechanism of how fasting supports autophagy isn't fully clear, the relationship between caloric restriction and autophagic response has been established in small human trials and several animal studies.² It's important to understand fasting is complex and should be done under the guise of a professional.

2. Autophagy & Key Nutrients - Several trials have explored supplements and or key nutrients for their effect on autophagy. Spermidine, a type of polyamine, has been associated with markers of age-related cellular health. A large prospective cohort study from 2018 showed higher dietary intake of spermidine was associated with lower mortality.³ Additional benefits of spermidine supplementation may  include: 

• boosting skin barrier function and hydration, 

• supporting collagen synthesis, 

• overall hair growth and more. 

3. Autophagy & Exercise - Exercise is incredibly important to cellular health and longevity. In vivo studies have shown physical exercise to be an inducer of autophagy.

4. Amino Acid and Protein signaling - Autophagy can be activated by a number of physiological stimuli such as nutrient availability- for example, increases in amino acids and protein activate mTOR (mammalian target of rapamycin) and suppress autophagy, while nutrient withdrawal activates autophagy.⁵ Learn more about the relationship between amino acids and cellular health.

5. Pharmacologic agents - Many pharmaceutical products are in research and development for supporting autophagy. These have various applications for human health and disease.

Frequently Asked Questions about Autophagy

Many conversations around autophagy focus on fasting—and we understand why. For most people, complete fasting isn’t practical. Research suggests autophagy is influenced less by calories alone and more by how nutrients signal to the body, particularly through pathways like mTOR (stimulated by amino acids) and AMPK (activated during low-energy, low-insulin states).⁵

Coffee and Autophagy 

Current animal studies suggest that black coffee does not break autophagy and may even support it through AMPK activation.⁶

Does Green Tea Break Autophagy?

Research on EGCG, the main phenolic compound in green tea, suggests plain green tea does not appear to suppress autophagy and may provide polyphenols that support cellular health.⁷

Does Creatine Break Autophagy?

There is no direct research on creatine and autophagy. However, creatine contains amino acids that can activate mTOR, so it may partially suppress fasting-induced autophagy.⁸ Therefore, creatine is ideal for performance and muscle building- not necessarily autophagic support.

Takeaway: Supporting Autophagy Through Lifestyle and Nutrients

Autophagy is a fundamental process that helps maintain cellular health, regulate energy, and support tissue maintenance throughout life. From fasting and exercise to nutrient signaling, a variety of lifestyle strategies can influence autophagic activity. While research is ongoing, nutrients like spermidine have emerged as promising tools to support this natural cellular recycling process.

For those interested in exploring spermidine as part of their longevity routine, Trū Renew contains 10 mg of spermidine per dose, designed to support autophagy and promote healthy cellular function*. Alongside lifestyle strategies like balanced nutrition, exercise, and mindful fasting, spermidine supplementation may help maintain cellular health and overall well-being*.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

 

References 

1. Gómez-Virgilio L, Silva-Lucero MD, Flores-Morelos DS, et al. Autophagy: A Key Regulator of Homeostasis and Disease: An Overview of Molecular Mechanisms and Modulators. Cells. 2022;11(15):2262. Published 2022 Jul 22. doi:10.3390/cells11152262 Link

2. Shabkhizan R, Haiaty S, Moslehian MS, et al. The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting. Adv Nutr. 2023;14(5):1211-1225. doi:10.1016/j.advnut.2023.07.006 Link

3. Kiechl S, Pechlaner R, Willeit P, et al. Higher spermidine intake is linked to lower mortality: a prospective population-based study. Am J Clin Nutr. 2018;108(2):371-380. doi:10.1093/ajcn/nqy102 Link

4. He C, Sumpter R Jr, Levine B. Exercise induces autophagy in peripheral tissues and in the brain. Autophagy. 2012;8(10):1548-1551. doi:10.4161/auto.21327 Link

5. Chung KW, Chung HY. The Effects of Calorie Restriction on Autophagy: Role on Aging Intervention. Nutrients. 2019;11(12):2923. Published 2019 Dec 2. doi:10.3390/nu11122923 Link

6. Pietrocola F, Malik SA, Mariño G, et al. Coffee induces autophagy in vivo. Cell Cycle. 2014;13(12):1987-1994. doi:10.4161/cc.28929 Link

7. Zhang S, Cao M, Fang F. The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseases. Med Sci Monit. 2020;26:e924558. Published 2020 Sep 10. doi:10.12659/MSM.924558 Link

8. Mateus O L, Franz W K, Marco M. Creatine Supplementation and Akt/mTOR Pathway: Unraveling the Connection for Optimal Muscle Performance. Journal of Sports Medicine and Therapy. 2023;8(2):024-029. doi:https://doi.org/10.29328/journal.jsmt.1001068  Link