Epigenetic Clocks and Neurodegenerative Diseases


Epigenetic clocks use changes in DNA methylation patterns across the genome to build predictive models that can estimate biological age, age-related diseases, assess the effects of environmental factors on aging, and evaluate the efficacy of anti-aging interventions. Because the global population are increasingly aging, neurodegenerative diseases are affecting more individuals, and therefore there is an urgent need to develop improved methods for early diagnosis, and to understand better mechanism of disease progression, and develop new treatment strategies. To this end, a new study published in the Journal of Neurology, Neurosurgery and Psychiatry, led by Professor Huifang Shang from the Department of Neurology at West China Hospital, Sichuan University, offers a comprehensive systemic review on the application of epigenetic clocks in neurodegenerative diseases. Conducted by Dr. Tianmi Yang, Yi Xiao, Yangfan Cheng, Jingxuan Huang, Qianqian Wei, and Chunyu Li, the research critically evaluates risk factors, age of onset, diagnosis, progression, prognosis, and pathology in Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). The authors identified studies that used epigenetic clocks with keywords related to ageing and DNA methylation. Afterward, they extracted the relevant data from the selected studies on study design, sample size, type of epigenetic clock used, biological tissues analyzed, main findings, and methodological approaches. They also assessed quality and risk of bias of the included studies to ensure the reliability and validity of the findings of their work. The approach they conducted aligned with the preferred reporting items for systematic reviews and meta-analyses guidelines. Their inclusion criteria focused on studies that reported data on the use of epigenetic clocks, which are biological markers that aim to provide a measure of an individual’s biological age based on DNA methylation patterns. These clocks calculate the methylation age of tissues and compare it to chronological age to determine age acceleration or deceleration. The authors successfully collected information from 23 studies that they used to reliably review the role of epigenetic clocks in neurodegenerative diseases.

With regard to AD, the authors said the epigenetic clocks revealed significant associations between accelerated DNA methylation age and common risk factors of AD, such as BMI and smoking. Some of the reported studies suggested that DNA methylation age could assist in predicting the age of onset and diagnosing AD through correlations with biomarkers like amyloid-beta and tau protein levels. Moreover, the progression of AD was also linked to changes in DNA methylation age, although findings were mixed across different studies and epigenetic clocks. On the other hand, studies showed that PD patients often had an accelerated DNA methylation age compared to controls. This acceleration was associated with earlier disease onset and more rapid progression of both motor and cognitive symptoms.  Another neurodegenerative disease they investigated was ALS and they showed DNA methylation age acceleration was linked to earlier disease onset. It also correlated with worse prognosis and higher risk of death, indicating its potential use as a prognostic marker in ALS. However, they reported limited data of DNA methylation age acceleration and progression in HD especially in relation to motor symptom severity.

Overall, the study by Professor Huifang Shang and her colleagues is significant because it enhanced our understanding of how accelerated biological aging correlates with the development and progression of neurodegenerative diseases. Moreover, their important epigenetic clocks in serving as valuable biomarkers for earlier and more accurate diagnosis of neurodegenerative diseases essential for effective treatment planning and patient care management. Furthermore, the establishment of a link between epigenetic age acceleration with neurodegenerative diseases, the authors open possibilities for new therapeutic interventions targeting the underlying aging processes that contribute to disease onset and progression. For instance, future research that identifies changes in DNA methylation age and its correlation with disease progression, researchers can identify new therapeutic targets that might slow or reverse epigenetic aging, and hence impact disease onset and progression. They also advocated to integrate epigenetic clocks into individual biological aging studies, which potentially will allow for more personalized medical interventions in neurology based on a person’s biological rather than chronological age.  Lastly, the expert opinion review of Professor Shang and team identified important knowledge gaps and called for the need for further longitudinal research to better use of epigenetic clocks, that can lead to the development of disease-specific, tissue-specific, or phenotype-specific clocks that better inform the molecular mechanisms of neurodegeneration.

About the author

Professor Shang is the Chief Physician in the Neurology Department at West China Hospital, Sichuan University. She has been honored as an Academic and Technical Leader in Sichuan Province and a Leading Talent in Health and Health Care in Sichuan Province, among other titles under the “Tianfu Qingcheng Plan” and the Tianfu Famous Doctor Program. Additionally, Professor Shang serves as a member of the National Health Commission’s Expert Committee on Diagnosis and Treatment and Assurance of Rare Diseases, leader of the Asia-Pacific Committee of the International Parkinson and Movement Disorder Society, and Executive Committee member of the Chinese Medical Association’s Rare Diseases Branch. Engaged in long-term clinical and basic research on neurodegenerative diseases, Professor Shang’s team has been building standardized neurodegenerative disease cohorts since 2006. They have conducted innovative research on amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), Huntington’s disease (HD), multiple system atrophy (MSA), dystonia (DYT), Alzheimer’s disease (AD), and other neurodegenerative and genetic diseases. Their research covers clinical features, genetic variations, and imaging molecular mechanisms of related diseases. As corresponding author, they have published over 300 SCI papers, secured funding for more than 10 projects from the National Natural Science Foundation, applied for over 10 invention patents, and authored or contributed to numerous neurology-related books.

About the author

Dr. Tianmi Yang is currently pursuing her doctoral studies in the Neurology Department at West China Hospital, Sichuan University, under the guidance of Professor Huifang Shang. Her research primarily centers on neurogenetics and neurodegenerative diseases, with a particular focus on understanding the pathogenesis and progression mechanisms of amyotrophic lateral sclerosis (ALS). She has contributed to the field with several publications in esteemed journals including JNNP, JOON, and Eur J Neurol.


Yang T, Xiao Y, Cheng Y, Huang J, Wei Q, Li C, Shang H. Epigenetic clocks in neurodegenerative diseases: a systematic review. J Neurol Neurosurg Psychiatry. 2023 Dec;94(12):1064-1070. doi: 10.1136/jnnp-2022-330931.

Go To J Neurol Neurosurg Psychiatry.