Targeting impaired nutrient sensing via the sirtuin pathway with novel compounds to prevent or treat dementia: A systematic review

Adrian Matysek; Lina Sun; Sumudu Perera Kimmantudawage; Lei Feng; Andrea B. Maier

doi:10.1016/j.arr.2023.102029

Targeting impaired nutrient sensing via the sirtuin pathway with novel compounds to prevent or treat dementia: A systematic review

Adrian Matysek, Lina Sun, Sumudu Perera Kimmantudawage, Lei Feng, Andrea B. Maier^*

^*Corresponding author for this work

Research output: Contribution to Journal › Review article › Academic › peer-review

Abstract

Background: Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small. Impaired nutrient sensing pathways have been implicated in the pathogenesis of dementia and may offer a novel treatment target. Aims: This systematic review collated evidence for novel therapeutic compounds that modify nutrient sensing pathways, particularly the sirtuin pathway, in preventing cognitive decline or improving cognition in normal ageing, mild cognitive impairment (MCI), and dementia. Methods: PubMed, Embase and Web of Science databases were searched using key search terms. Articles were screened using Covidence systematic review software. The risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE)’s risk of bias tool for animal studies and Cochrane Risk of Bias tool v 2.0 for human studies. Results: Out of 3841 articles, 68 were included describing 38 different novel therapeutic compounds that modulate the nutrient sensing pathway via the sirtuin pathway. In animal models (58 studies), all investigated novel therapeutic compounds showed cognitive benefits. Ten studies were human intervention trials targeting normal ageing (1 study) and dementia populations (9 studies). Direct sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) activators Resveratrol and Nicotinamide derivatives improved cognitive outcomes among human subjects with normal cognition and MCI. Conclusion: Animal studies support that modulation of the sirtuin pathway has the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.

Original language	English
Article number	102029
Pages (from-to)	1-11
Number of pages	11
Journal	Ageing Research Reviews
Volume	90
Early online date	6 Aug 2023
DOIs	https://doi.org/10.1016/j.arr.2023.102029
Publication status	Published - Sept 2023

Bibliographical note

Funding Information:
An unrestricted grant by the University of Melbourne supported the work. We thank Patrick Condron from the Brownless Biomedical Library, University of Melbourne, for his assistance with the search strategy.

Funding Information:
An unrestricted grant by the University of Melbourne supported the work. We thank Patrick Condron from the Brownless Biomedical Library, University of Melbourne, for his assistance with the search strategy.

Publisher Copyright:
© 2023 The Authors

Keywords

Aging
Alzheimer's disease
Cognition
Dementia
Sirtuin
Therapeutics

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@article{ca44c4f36487476fb8dca55f647496eb,

title = "Targeting impaired nutrient sensing via the sirtuin pathway with novel compounds to prevent or treat dementia: A systematic review",

abstract = "Background: Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small. Impaired nutrient sensing pathways have been implicated in the pathogenesis of dementia and may offer a novel treatment target. Aims: This systematic review collated evidence for novel therapeutic compounds that modify nutrient sensing pathways, particularly the sirtuin pathway, in preventing cognitive decline or improving cognition in normal ageing, mild cognitive impairment (MCI), and dementia. Methods: PubMed, Embase and Web of Science databases were searched using key search terms. Articles were screened using Covidence systematic review software. The risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE){\textquoteright}s risk of bias tool for animal studies and Cochrane Risk of Bias tool v 2.0 for human studies. Results: Out of 3841 articles, 68 were included describing 38 different novel therapeutic compounds that modulate the nutrient sensing pathway via the sirtuin pathway. In animal models (58 studies), all investigated novel therapeutic compounds showed cognitive benefits. Ten studies were human intervention trials targeting normal ageing (1 study) and dementia populations (9 studies). Direct sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) activators Resveratrol and Nicotinamide derivatives improved cognitive outcomes among human subjects with normal cognition and MCI. Conclusion: Animal studies support that modulation of the sirtuin pathway has the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.",

keywords = "Aging, Alzheimer's disease, Cognition, Dementia, Sirtuin, Therapeutics",

author = "Adrian Matysek and Lina Sun and Kimmantudawage, {Sumudu Perera} and Lei Feng and Maier, {Andrea B.}",

note = "Funding Information: An unrestricted grant by the University of Melbourne supported the work. We thank Patrick Condron from the Brownless Biomedical Library, University of Melbourne, for his assistance with the search strategy. Funding Information: An unrestricted grant by the University of Melbourne supported the work. We thank Patrick Condron from the Brownless Biomedical Library, University of Melbourne, for his assistance with the search strategy. Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = sep,

doi = "10.1016/j.arr.2023.102029",

language = "English",

volume = "90",

pages = "1--11",

journal = "Ageing Research Reviews",

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T1 - Targeting impaired nutrient sensing via the sirtuin pathway with novel compounds to prevent or treat dementia

T2 - A systematic review

AU - Matysek, Adrian

AU - Sun, Lina

AU - Kimmantudawage, Sumudu Perera

AU - Feng, Lei

AU - Maier, Andrea B.

N1 - Funding Information: An unrestricted grant by the University of Melbourne supported the work. We thank Patrick Condron from the Brownless Biomedical Library, University of Melbourne, for his assistance with the search strategy. Funding Information: An unrestricted grant by the University of Melbourne supported the work. We thank Patrick Condron from the Brownless Biomedical Library, University of Melbourne, for his assistance with the search strategy. Publisher Copyright: © 2023 The Authors

PY - 2023/9

Y1 - 2023/9

N2 - Background: Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small. Impaired nutrient sensing pathways have been implicated in the pathogenesis of dementia and may offer a novel treatment target. Aims: This systematic review collated evidence for novel therapeutic compounds that modify nutrient sensing pathways, particularly the sirtuin pathway, in preventing cognitive decline or improving cognition in normal ageing, mild cognitive impairment (MCI), and dementia. Methods: PubMed, Embase and Web of Science databases were searched using key search terms. Articles were screened using Covidence systematic review software. The risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE)’s risk of bias tool for animal studies and Cochrane Risk of Bias tool v 2.0 for human studies. Results: Out of 3841 articles, 68 were included describing 38 different novel therapeutic compounds that modulate the nutrient sensing pathway via the sirtuin pathway. In animal models (58 studies), all investigated novel therapeutic compounds showed cognitive benefits. Ten studies were human intervention trials targeting normal ageing (1 study) and dementia populations (9 studies). Direct sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) activators Resveratrol and Nicotinamide derivatives improved cognitive outcomes among human subjects with normal cognition and MCI. Conclusion: Animal studies support that modulation of the sirtuin pathway has the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.

AB - Background: Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small. Impaired nutrient sensing pathways have been implicated in the pathogenesis of dementia and may offer a novel treatment target. Aims: This systematic review collated evidence for novel therapeutic compounds that modify nutrient sensing pathways, particularly the sirtuin pathway, in preventing cognitive decline or improving cognition in normal ageing, mild cognitive impairment (MCI), and dementia. Methods: PubMed, Embase and Web of Science databases were searched using key search terms. Articles were screened using Covidence systematic review software. The risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE)’s risk of bias tool for animal studies and Cochrane Risk of Bias tool v 2.0 for human studies. Results: Out of 3841 articles, 68 were included describing 38 different novel therapeutic compounds that modulate the nutrient sensing pathway via the sirtuin pathway. In animal models (58 studies), all investigated novel therapeutic compounds showed cognitive benefits. Ten studies were human intervention trials targeting normal ageing (1 study) and dementia populations (9 studies). Direct sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) activators Resveratrol and Nicotinamide derivatives improved cognitive outcomes among human subjects with normal cognition and MCI. Conclusion: Animal studies support that modulation of the sirtuin pathway has the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.

KW - Aging

KW - Alzheimer's disease

KW - Cognition

KW - Dementia

KW - Sirtuin

KW - Therapeutics

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DO - 10.1016/j.arr.2023.102029

M3 - Review article

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SN - 1568-1637

VL - 90

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JO - Ageing Research Reviews

JF - Ageing Research Reviews

M1 - 102029

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Targeting impaired nutrient sensing via the sirtuin pathway with novel compounds to prevent or treat dementia: A systematic review

Abstract

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Keywords

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