image: Figure 4. Spermidine protects from memory amelioration in both 12% yeast and 2% yeast diets as well as boosts fecundity in 12% yeast in mid-age flies. Intermediate-term memory (ITM) of 3-day (A) and 30-day (B) old isogenic w1118 flies, bred on either 12% or 2% food with or without the addition of 5 mM spermidine (n = 11 – 13 biological replicates. Each biological replicate contains around 70 flies). (C–E) Fecundity assay of isogenic w1118 female flies bred on 12% yeast and 2% yeast with and without the addition of 5 mM spermidine at early-, mid- and old-age respectively (n = 11 biological replicates). *p < 0.05, **p < 0.01, ***p < 0.001, ****p< 0.0001, ns, not significant. Data are mean ± SEM. P-values were determined by 2-way ANOVA with Tukey’s post hoc multiple comparisons test (A – E).
Credit: Copyright: © 2025 Liang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“Our findings suggest that while both protein restriction and spermidine supplementation improve brain mitochondrial function, they largely operate through distinct mechanisms in modulating Drosophila brain aging.”
BUFFALO, NY — July 10, 2025 — A new research paper was published in Aging (Aging-US) Volume 17, Issue 6, on June 7, 2025, titled “Spermidine supplementation and protein restriction protect from organismal and brain aging independently.”
In this study, led by YongTian Liang and Stephan J. Sigrist from Freie Universität Berlin, Charité Universitätmediz Berlin, and the Leibniz-German Center for Neurodegenerative Diseases (DZNE), researchers investigated how spermidine, a natural substance in the body, and protein intake levels influence aging in fruit flies. They found that spermidine supplementation and changes in protein intake influenced brain health and aging in distinct ways. These insights could guide the development of new strategies to slow age-related decline in humans.
“In this study, we combined low- and high-protein diets (2% versus 12% yeast in food) with spermidine supplementation in aging Drosophila fruit flies.”
Aging of the brain and body contributes to cognitive decline and diseases in older populations. Scientists have long explored dietary restriction and fasting as ways to slow these processes. This study reveals that spermidine supplementation supports brain health by enhancing mitochondrial function and memory, while protein restriction independently promotes longevity and protects against movement decline.
The researchers discovered that spermidine improved memory and preserved physical activity in aging flies regardless of protein intake. In contrast, reducing protein alone boosted mitochondrial activity and extended lifespan without directly enhancing memory. Importantly, the combined approach of protein restriction and spermidine supplementation provided additive benefits, suggesting potential for synergistic effects.
This work highlights that spermidine acts through a pathway involving hypusination, a vital process where cells modify proteins to support energy production and repair, while protein restriction works via nutrient-sensing pathways that promote longevity. These independent mechanisms may explain why combining the two interventions offers greater protection against aging effects.
Although conducted in flies, the study underscores the possibility of designing dietary and supplement-based interventions to combat human age-related decline. As spermidine levels naturally decline with age, supplementation combined with moderated protein intake could offer a safe way to promote brain health and longevity in humans.
The authors point out that it takes further studies in mammals and humans to validate these results. If confirmed, such strategies could lead the way for accessible approaches to promote healthy aging and reduce the burden of cognitive disorders in older populations.
Read the full paper: DOI: https://doi.org/10.18632/aging.206267
Corresponding authors: YongTian Liang – yongtian.tim.liang@gmail.com; Stephan J. Sigrist – stephan.sigrist@fu-berlin.de
Keywords: aging, brain aging, spermidine, protein restriction, mitochondria
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Journal
Aging-US
Method of Research
News article
Subject of Research
Animals
Article Title
Spermidine supplementation and protein restriction protect from organismal and brain aging independently
Article Publication Date
7-Jun-2025
COI Statement
T.E. and S.J.S conducted paid consultancy for TLL (The Longevity Labs).