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Synergistic Anti-Aging Effects of mTOR and SGLT-2 Inhibitors

Lasse Damgaard Harreskov by Lasse Damgaard Harreskov
April 24, 2025
Reading Time: 4 mins read

Study: “mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes”
Publisher: IJMS
Published date: August 2024
PubMed link to study: https://pubmed.ncbi.nlm.nih.gov/39201363/

A recent research review published by International Journal of Molecular Sciences (IJMS) suggests that combining mTOR inhibitors and SGLT-2 inhibitors could provide benefits in slowing down the aging process.

mTOR inhibitors help enhance autophagy (the body’s process of clearing damaged cells), while SGLT-2 inhibitors improve metabolic health by promoting calorie restriction-like effects. Together, these drugs may target key aging mechanisms, potentially extending healthspan and reducing age-related cellular dysfunction.

Feel welcome to share your own thoughts on this research in the comment section below as well. I will be happy to discuss and learn more about how you see its potential in this field.

The Science of Aging and Cellular Senescence

Aging is closely linked to the accumulation of senescent cells, which are cells that have stopped dividing but remain metabolically active. These cells contribute to chronic inflammation and tissue dysfunction, playing a major role in age-related diseases such as cardiovascular disease, diabetes, and neurodegeneration.

Removing or neutralizing these cells is a core goal in anti-aging research. mTOR inhibitors and SGLT-2 inhibitors are two promising drug classes that may address this issue by targeting key aspects of cellular metabolism and stress responses.

What are mTOR and SGLT-2 Inhibitors?

mTOR Inhibitors

The mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating cell growth, metabolism, and aging. Overactivation of this pathway can promote aging and age-related diseases. mTOR inhibitors, such as rapamycin, work by reducing the activity of this pathway, thereby enhancing autophagy—the body’s natural process of cleaning out damaged cells and recycling cellular components.

SGLT-2 Inhibitors

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are primarily used for managing type 2 diabetes. They reduce blood sugar levels by preventing glucose reabsorption in the kidneys. However, recent studies have shown that these drugs may also influence cellular aging by promoting metabolic changes that mimic the effects of calorie restriction—a well-known strategy to extend lifespan in various organisms.

A Synergistic Effect Against Aging

Combining mTOR inhibitors with SGLT-2 inhibitors could have complementary actions that reduce cellular senescence. mTOR inhibitors promote autophagy and reduce inflammation, which helps the body clear out damaged cells and proteins. SGLT-2 inhibitors, on the other hand, induce a fasting-like state, activating energy-sensing pathways such as AMPK and sirtuins, which are associated with improved metabolic health and longevity.

This combination could lead to several beneficial effects:

  1. Enhanced Autophagy: Both drug classes activate pathways that boost autophagy, leading to improved cellular maintenance and reduced accumulation of damaged components that contribute to aging.
  2. Reduced Inflammation: mTOR inhibitors are known to reduce inflammatory signals, while SGLT-2 inhibitors help mitigate the inflammation caused by high glucose levels, often seen in older individuals.
  3. Improved Metabolic Health: By mimicking the effects of caloric restriction, SGLT-2 inhibitors may help optimize the body’s metabolic functions, making it easier for cells to maintain energy balance and reduce age-related metabolic dysfunction.

Current Research and Future Prospects

Though direct studies on the combined effects of these two drug types are still limited, preliminary research suggests that their synergy could provide significant anti-aging benefits.

Animal studies have shown that mTOR inhibition can extend lifespan, while SGLT-2 inhibitors are linked to reduced markers of cellular stress and improved metabolic health. Together, these effects could help reduce the burden of senescent cells, promote tissue rejuvenation, and ultimately extend healthspan—the portion of life spent in good health.

However, it is important to note that both mTOR and SGLT-2 inhibitors have potential side effects that need careful management, particularly in older populations. Further research, including clinical trials in humans, is crucial to understand the safety, efficacy, and long-term impact of these drugs when used together as an anti-aging strategy.

In Summary

The potential of mTOR and SGLT-2 inhibitors to combat aging lies in their ability to address cellular senescence via enhanced autophagy and metabolic optimization, which is considered one of the most important processes in aging. While more research is needed, especially involving human trials, this approach represents a promising area in the pursuit to extend both lifespan and healthspan.

I am curious to know what your thoughts are on these findings. Could this synergistic effect between mTOR and SGLT-2 inhibitors be they key we are looking for in the field of anti-aging research? Leave a comment below.

Read about more anti-aging research.

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Pursuit of Immortality

At Pursuit of Immortality I will keep you updated on the latest scientific research and technological breakthroughs in the field of anti-aging, and explore the question of whether it is possible to live forever.

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