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Review
. 2024 Jan 23;13(1):7.
doi: 10.1186/s40035-024-00397-x.

The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing

Yuqing Liu  1   2 , Yejun Tan  3 , Zheyu Zhang  1   2 , Min Yi  1   2 , Lemei Zhu  4 , Weijun Peng  5   6
Affiliations
Review

The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing

Yuqing Liu et al. Transl Neurodegener. .

Abstract

Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of ageing-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments, indicating that ageing plays a crucial role in the pathophysiological process of AD. In this review, we summarize the impact of several age-related factors on AD and propose that preventing pathological changes caused by brain ageing is a promising strategy for improving cognitive health.

Keywords: Alzheimer’s disease; Anti-ageing therapy; Brain ageing; Cell senescence; Chronic inflammation; Hallmarks of ageing.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Intracellular hallmarks of ageing in AD. The intracellular hallmarks of ageing include genomic instability, macromolecular damage, epigenetic alterations, deregulated nutrient sensing and mitochondrial dysfunction. Additionally, protein damage in AD mainly manifests as the abnormal aggregation of Aβ and tau proteins, which is related to cerebral insulin resistance and affects nutrient sensing in nerve cells [19]. The green arrow indicates that IGF-1R is downregulated in the brain tissues of patients with AD [20]. AD Alzheimer’s disease, ncRNAs non-coding RNAs, lncRNA long non-coding RNA, miRNA microRNA, circRNA circular RNA
Fig. 2
Fig. 2
Cellular hallmarks of ageing in AD, including cellular senescence, disabled macroautophagy, stem cell exhaustion and altered intercellular communication. ROS activated by Aβ and tau can cause stress-induced cellular senescence [10, 152]. The senescent cells exhibit significant dysfunction and abnormal intercellular communication. Ageing microglia release more pro-inflammatory factors and have impaired phagocytic function [153]. Simultaneously, stem cell exhaustion inhibits the transformation of stem cells into neurons, astrocytes and oligodendrocytes [154]. AD Alzheimer’s disease, ROS reactive oxygen species, P16INK4a a marker of cellular senescence
Fig. 3
Fig. 3
Changes in systemic ageing markers between normal and ageing (in AD) brains. Microbiota homeostasis maintains normal nutrient metabolism, immune defense and signaling transduction to the brain and other organs [229]. Dysbiosis, including decreased diversity of microbiota, decreased abundance of beneficial microbes, increased abundance of harmful microbes and decreased levels of bile acids and SCFAs, can cause a persistent inflammatory reaction [230]. Moreover, disruption of the BBB allows macrophages to enter the brain and aggravate neuroinflammation [231]. AD Alzheimer’s disease, SCFAs short-chain fatty acids
See this image and copyright information in PMC

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