Transient rapamycin treatment during developmental stage extends lifespan in <i>Mus musculus</i> and <i>Drosophila melanogaster</i>

Aiello, Giuseppe; Sabino, Cosimo; Pernici, Davide; Audano, Matteo; Antonica, Francesco; Gianesello, Matteo; Ballabio, Claudio; Quattrone, Alessandro; Mitro, Nico; Romanel, Alessandro; Soldano, Alessia; Tiberi, Luca

doi:10.15252/embr.202255299

Cited by 24 publications

(26 citation statements)

References 46 publications

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“…What is remarkable though is that lifelong treatment with rapamycin was safe (no increase in mortality) and effective (an increase in longevity) in mice [2] and Drosophila [1,2]. The results of these studies agree with the predictions of hyperfunction theory of mTOR-driven quasi-program of aging.…”

Section: Introduction "Brief" Treatment In Flies and Micesupporting

confidence: 74%

“…The dose was high enough to almost completely block mouse growth. By day 30, rapamycin-treated mice were three times smaller than control mice [2]. Treatment from 30 to 60 days did not increase lifespan [2].…”

Section: Introduction "Brief" Treatment In Flies and Micementioning

confidence: 86%

“…In a complementary study, Aiello et al [2] found that rapamycin treatment immediately after birth increased lifespan in Mus musculus (house mouse); the same treatment started later had no effect on lifespan [2]. In mice, the treatment with high doses of rapamycin, from birth to age 30 days, increased median lifespan by 9.6% [2].…”

Section: Introduction "Brief" Treatment In Flies and Micementioning

confidence: 99%

“…Noteworthy, the "brief" treatment is not brief, it is an equivalent to 3-20 years of human life, as we will discuss. Furthermore, started at birth, rapamycin treatment severely inhibited developmental growth [2,3].…”

Section: Introduction "Brief" Treatment In Flies and Micementioning

confidence: 99%

“…This seems exciting on the surface. However, according to these well-executed studies in mice and flies, rapamycin treatment should be started at birth (or shortly after birth) to be most effective [1][2][3]. So, it's definitely too late for anyone capable of reading this article.…”

Section: Introduction "Brief" Treatment In Flies and Micementioning

confidence: 99%

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Rapamycin treatment early in life reprograms aging: hyperfunction theory and clinical practice

Blagosklonny

2022

Aging

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Making provocative headlines, three outstanding publications demonstrated that early-life treatment with rapamycin, including treatments during developmental growth, extends lifespan in animals, confirming predictions of hyperfunction theory, which views aging as a quasi-program (an unintended continuation of developmental growth) driven in part by mTOR. Despite their high theoretical importance, clinical applications of two of these studies in mice, Drosophila and Daphnia cannot be implemented in humans because that would require growth retardation started at birth. A third study demonstrated that a transient (around 20% of total lifespan in Drosophila) treatment with rapamycin early in Drosophila adult life is as effective as lifelong treatment, whereas a late-life treatment is not effective. However, previous studies in mice demonstrated that a transient late-life treatment is highly effective. Based on hyperfunction theory, this article attempts to reconcile conflicting results and suggests the optimal treatment strategy to extend human lifespan.

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Section: Introduction "Brief" Treatment In Flies and Micesupporting

confidence: 74%

Section: Introduction "Brief" Treatment In Flies and Micementioning

confidence: 86%

Section: Introduction "Brief" Treatment In Flies and Micementioning

confidence: 99%

Section: Introduction "Brief" Treatment In Flies and Micementioning

confidence: 99%

Section: Introduction "Brief" Treatment In Flies and Micementioning

confidence: 99%

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Rapamycin treatment early in life reprograms aging: hyperfunction theory and clinical practice

Blagosklonny

2022

Aging

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Low‐Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe

Ohtsuka,

Shimasaki,

Aiba

2024

Advanced Biology

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Yeast is an excellent model organism for research for regulating aging and lifespan, and the studies have made many contributions to date, including identifying various factors and signaling pathways related to aging and lifespan. More than 20 years have passed since molecular biological perspectives are adopted in this research field, and intracellular factors and signal pathways that control aging and lifespan have evolutionarily conserved from yeast to mammals. Furthermore, these findings have been applied to control the aging and lifespan of various model organisms by adjustment of the nutritional environment, genetic manipulation, and drug treatment using low‐molecular weight compounds. Among these, drug treatment is easier than the other methods, and research into drugs that regulate aging and lifespan is consequently expected to become more active. Chronological lifespan, a definition of yeast lifespan, refers to the survival period of a cell population under nondividing conditions. Herein, low‐molecular weight compounds are summarized that extend the chronological lifespan of Saccharomyces cerevisiae and Schizosaccharomyces pombe, along with their intracellular functions. The low‐molecular weight compounds are also discussed that extend the lifespan of other model organisms. Compounds that have so far only been studied in yeast may soon extend lifespan in other organisms.

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Devo-Aging: Intersections Between Development and Aging

Silva-García

2023

GeroScience

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There are two fundamental questions in developmental biology. How does a single fertilized cell give rise to a whole body? and how does this body later produce progeny? Synchronization of these embryonic and postembryonic developments ensures continuity of life from one generation to the next. An enormous amount of work has been done to unravel the molecular mechanisms behind these processes, but more recently, modern developmental biology has been expanded to study development in wider contexts, including regeneration, environment, disease, and even aging. However, we have just started to understand how the mechanisms that govern development also regulate aging. This review discusses examples of signaling pathways involved in development to elucidate how their regulation influences healthspan and lifespan. Therefore, a better knowledge of developmental signaling pathways stresses the possibility of using them as innovative biomarkers and targets for aging and age-related diseases.

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Transient rapamycin treatment during developmental stage extends lifespan in Mus musculus and Drosophila melanogaster

Cited by 24 publications

References 46 publications

Rapamycin treatment early in life reprograms aging: hyperfunction theory and clinical practice

Rapamycin treatment early in life reprograms aging: hyperfunction theory and clinical practice

Low‐Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe

Devo-Aging: Intersections Between Development and Aging

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