Molecular mechanisms of exceptional lifespan increase of Drosophila melanogaster with different genotypes after combinations of pro-longevity interventions

Shaposhnikov, Mikhail; Guvatova, Zulfiya G.; Zemskaya, Nadezhda; Koval, Liubov; Schegoleva, Eugenia V.; Gorbunova, Anastasia A.; Golubev, Denis A.; Pakshina, Natalya R.; Ulyasheva, Natalia S.; Solovev, Ilya; Bobrovskikh, Margarita A.; Грунтенко, Н. Е.; Menshanov, Petr N.; Krasnov, George S.; Kudryavseva, Anna V.; Moskalev, Alexey

doi:10.1038/s42003-022-03524-4

Cited by 14 publications

(11 citation statements)

References 108 publications

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“…Our results unambiguously reinforce that DR can reliably increase lifespan in flies at standard lab conditions across different temperatures. As such our work fits with earlier work that used a combination of life-extending treatments, including temperature and DR, and found them to be largely additive (Kim et al, 2020; Shaposhnikov et al, 2022). Our findings and this prior literature contradict those of a recent study (Zajitschek et al, 2023) and counter their argument that DR constitutes a lab artefact.…”

Section: Discussionsupporting

confidence: 88%

“…That a clear positive control, namely DR extending lifespan consistently, is missing further limits what we can interpret from this prior study. Our work here, supported by prior published work by others (Kim et al, 2020;Shaposhnikov et al, 2022), does not support the interpretation that DR is a lab artefact and that DR would therefore not extend lifespan in the wild (Zajitschek et al, 2023). Even though conditions, environmental or genetic, that modulate the DR response are a valuable tool forward to understanding the DR response and ageing more generally (Simons & Dobson, 2023), it deters progress if such contrary findings are overinterpreted, especially when they are interpreted to have a broader ecological, evolutionary and physiological relevance.…”

Section: Discussionsupporting

confidence: 88%

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Dietary restriction extends lifespan across different temperatures in the fly

Phillips,

Simons

2023

Preprint

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Dietary restriction (DR) has been consistently shown to extend lifespan across a range of taxa. However, it has recently been reported that DR does not extend lifespan at certain, namely lower, temperatures in flies (Drosophila melanogaster). Similar to the interpretation of other findings that appear to question DR's universality, this finding has been interpreted as being an artefact of benign laboratory conditions. Here we re-test this hypothesis, now using a strain that shows robust lifespan extension at 25C (across three prior experiments), and using a range of 5 diets across two temperatures, 18C and 21C. We found the DR longevity response to be robust, extending lifespan irrespective of temperature. We measured fecundity as a positive control for the DR phenotype, and found, as predicted, that DR reduces egg laying. It will be important for results that question DR as a phenotype to not be overinterpreted readily, as with a substantially larger sample size and a larger range of diets we were unable to replicate this prior work. Differences in experimental setup, genetic lines used and variation in the diet-lifespan reaction norm we suggest are responsible for this discrepancy. In addition, starting with a strain and conditions that show a lifespan extension by DR, as we do here, and then changing environment and/or genotype promises a more robust test of DR modulating factors.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 88%

Dietary restriction extends lifespan across different temperatures in the fly

Phillips,

Simons

2023

Preprint

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“…In this regard, Shaposhnikov et al . recently demonstrated a synergistic effect by targeting multiple aging hallmarks simultaneously, producing a significant increase in Drosophila melanogaster lifespan compared to single interventions (Shaposhnikov et al ., 2022).…”

Section: Discussionmentioning

confidence: 99%

“…In this line, attempts to induce multiparameter amelioration are now emerging as a strategy for rejuvenation even outside the field of cellular reprogramming. In this regard, Shaposhnikov et al recently demonstrated a synergistic effect by targeting multiple aging hallmarks simultaneously, producing a significant increase in Drosophila melanogaster lifespan compared to single interventions (Shaposhnikov et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan

Schonfeldt

Paine

et al. 2022

Preprint

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The dedifferentiation of somatic cells into a pluripotent state by cellular reprogramming coincides with a reversal of age-associated molecular hallmarks. Although transcription factor induced cellular reprogramming has been shown to ameliorate these aging phenotypes in human cells and extend health and lifespan in mice, translational applications of this approach are still limited. More recently, chemical reprogramming via small molecule cocktails have demonstrated a similar ability to induce pluripotency in vitro, however, its potential impact on aging is unknown. Here, we demonstrated that partial chemical reprogramming is able to improve key drivers of aging including genomic instability and epigenetic alterations in aged human cells. Moreover, we identified an optimized combination of two reprogramming molecules sufficient to induce the amelioration of additional aging phenotypes including cellular senescence and oxidative stress. Importantly, in vivo application of this two-chemical combination significantly extended C. elegans lifespan. Together, these data demonstrate that improvement of key drivers of aging and lifespan extension is possible via chemical induced partial reprogramming, opening a path towards future translational applications.

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“…Drosophila overwinters in nature in the adult stage in vegetable warehouses, etc., wherever the temperature reaches 16 °C. At this temperature, the duration of lifespan of adult flies is significantly lengthened [ 13 ].…”

Section: Advantages Of Drosophila As a Highly Info...mentioning

confidence: 99%

Drosophila as a Model Organism to Study Basic Mechanisms of Longevity

Ogienko

Omelina

Bylino

et al. 2022

IJMS

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The spatio-temporal regulation of gene expression determines the fate and function of various cells and tissues and, as a consequence, the correct development and functioning of complex organisms. Certain mechanisms of gene activity regulation provide adequate cell responses to changes in environmental factors. Aside from gene expression disorders that lead to various pathologies, alterations of expression of particular genes were shown to significantly decrease or increase the lifespan in a wide range of organisms from yeast to human. Drosophila fruit fly is an ideal model system to explore mechanisms of longevity and aging due to low cost, easy handling and maintenance, large number of progeny per adult, short life cycle and lifespan, relatively low number of paralogous genes, high evolutionary conservation of epigenetic mechanisms and signalling pathways, and availability of a wide range of tools to modulate gene expression in vivo. Here, we focus on the organization of the evolutionarily conserved signaling pathways whose components significantly influence the aging process and on the interconnections of these pathways with gene expression regulation.

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Molecular mechanisms of exceptional lifespan increase of Drosophila melanogaster with different genotypes after combinations of pro-longevity interventions

Cited by 14 publications

References 108 publications

Dietary restriction extends lifespan across different temperatures in the fly

Dietary restriction extends lifespan across different temperatures in the fly

Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan

Drosophila as a Model Organism to Study Basic Mechanisms of Longevity

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