TY - JOUR
T1 - Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease
AU - Babygirija, Reji
AU - Sonsalla, Michelle M.
AU - Mill, Jericha
AU - James, Isabella
AU - Han, Jessica H.
AU - Green, Cara L.
AU - Calubag, Mariah F.
AU - Wade, Gina
AU - Tobon, Anna
AU - Michael, John
AU - Trautman, Michaela M.
AU - Matoska, Ryan
AU - Yeh, Chung Yang
AU - Grunow, Isaac
AU - Pak, Heidi H.
AU - Rigby, Michael J.
AU - Baldwin, Dominique A.
AU - Niemi, Natalie M.
AU - Denu, John M.
AU - Puglielli, Luigi
AU - Simcox, Judith
AU - Lamming, Dudley W.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer’s disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.
AB - Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer’s disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.
UR - http://www.scopus.com/inward/record.url?scp=85196140948&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-49589-z
DO - 10.1038/s41467-024-49589-z
M3 - Article
C2 - 38890307
AN - SCOPUS:85196140948
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5217
ER -