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Early, pulsatile use of rapamycin promoted longevity in two preclinical models

News
September 9, 2022
By
Ehab Naim, MBA.

The researchers concluded that early, brief rapamycin exposure confers geroprotective effects similar to lifelong treatment without the adverse effects of chronic dosing.

Rapamycin is a macrolide (a class of medication) that acts by inhibiting the target of rapamycin complex 1, extending the lifespan of preclinical models like mice. Research has shown that rapamycin delays age-related diseases in mice, like cognitive decline, immune dysfunction, and cardiovascular disorders. However, long-term use, even at small doses, has been linked to adverse events. In older humans, short-term use has been suggested to provide the positive effects of lifespan extension and immune enhancement. It is unknown whether the outcomes of late-life exposure to rapamycin are similar to the effects of lifelong use or brief treatment with the medication at younger ages.

Juricic et al. sought to demonstrate how brief pulse exposure to rapamycin (added to food) during early adulthood could produce geroprotective effects similar to chronic drug treatment. The researchers used two model organisms – Drosophila (fruit fly) and mice.

In the Drosophila model, the lifespan of females treated with rapamycin was significantly extended compared to males across different ages and treatment durations. In addition, results showed that treatment starting at later life stages (day 30 or 45) extends the lifespan but less than lifelong treatment. The latter is consistent with previous research findings on mice. Very late treatment onset (from day 60) did not increase the lifespan. This means that later-onset rapamycin treatment produced progressively smaller lifespan extension.

Contrary to the previous, rapamycin treatment in early adulthood extended the lifespan as much as lifetime dosing did. In this context, treatment with rapamycin in Drosophila's first 15 days of adult life produced a similar longevity promotion to chronic treatment. The said phenomenon is called "rapamycin memory". In mice, early life treatment for three months induced the “memory” effect similar to that of chronic treatment.

The researchers concluded that early, brief rapamycin exposure confers geroprotective effects similar to lifelong treatment without the adverse effects of chronic dosing. Further research is required to determine an optimal dosing regimen that maximizes the benefits while minimizing side effects.

 

 

Source: Juricic, P., Lu, YX., Leech, T. et al. Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy. Nat Aging (2022). https://doi.org/10.1038/s43587-022-00278-w

Rapamycin is a macrolide (a class of medication) that acts by inhibiting the target of rapamycin complex 1, extending the lifespan of preclinical models like mice. Research has shown that rapamycin delays age-related diseases in mice, like cognitive decline, immune dysfunction, and cardiovascular disorders. However, long-term use, even at small doses, has been linked to adverse events. In older humans, short-term use has been suggested to provide the positive effects of lifespan extension and immune enhancement. It is unknown whether the outcomes of late-life exposure to rapamycin are similar to the effects of lifelong use or brief treatment with the medication at younger ages.

Juricic et al. sought to demonstrate how brief pulse exposure to rapamycin (added to food) during early adulthood could produce geroprotective effects similar to chronic drug treatment. The researchers used two model organisms – Drosophila (fruit fly) and mice.

In the Drosophila model, the lifespan of females treated with rapamycin was significantly extended compared to males across different ages and treatment durations. In addition, results showed that treatment starting at later life stages (day 30 or 45) extends the lifespan but less than lifelong treatment. The latter is consistent with previous research findings on mice. Very late treatment onset (from day 60) did not increase the lifespan. This means that later-onset rapamycin treatment produced progressively smaller lifespan extension.

Contrary to the previous, rapamycin treatment in early adulthood extended the lifespan as much as lifetime dosing did. In this context, treatment with rapamycin in Drosophila's first 15 days of adult life produced a similar longevity promotion to chronic treatment. The said phenomenon is called "rapamycin memory". In mice, early life treatment for three months induced the “memory” effect similar to that of chronic treatment.

The researchers concluded that early, brief rapamycin exposure confers geroprotective effects similar to lifelong treatment without the adverse effects of chronic dosing. Further research is required to determine an optimal dosing regimen that maximizes the benefits while minimizing side effects.

 

 

Source: Juricic, P., Lu, YX., Leech, T. et al. Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy. Nat Aging (2022). https://doi.org/10.1038/s43587-022-00278-w

Article reviewed by
Dr. Ana Baroni MD. Ph.D.
SCIENTIFIC & MEDICAL ADVISOR
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Dr. Ana Baroni MD. Ph.D.

Scientific & Medical Advisor
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Ana has over 20 years of consultancy experience in longevity, regenerative and precision medicine. She has a multifaceted understanding of genomics, molecular biology, clinical biochemistry, nutrition, aging markers, hormones and physical training. This background allows her to bridge the gap between longevity basic sciences and evidence-based real interventions, putting them into the clinic, to enhance the healthy aging of people. She is co-founder of Origen.life, and Longevityzone. Board member at Breath of Health, BioOx and American Board of Clinical Nutrition. She is Director of International Medical Education of the American College of Integrative Medicine, Professor in IL3 Master of Longevity at Barcelona University and Professor of Nutrigenomics in Nutrition Grade in UNIR University.

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