Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond
Abstract
:1. Introduction
2. Biomolecular Aspects of Aging
3. Aging of Organs and Systems beyond Neurodegeneration
4. Limitations of the AA Concept
5. Recommendations for Further Development and Improvement of AA Concept
5.1. Statistical Models
- ○
- Sample size. The number of individuals in the study can affect the statistical power of the analysis, and larger sample sizes generally provide more robust results.
- ○
- Biomarker types. The choice of biomarkers can impact the diagnostic model used, as different types of biomarkers may require different statistical analyses.
- ○
- Age range. The age range of the study population can influence the types of biomarkers identified, as some biomarkers may be more prevalent in certain age groups.
- ○
- Data normalization. Normalization of the data is critical to ensure that data collection or processing differences do not affect the analysis.
- ○
- Statistical methods. The choice of statistical methods used can impact the sensitivity and specificity of the analysis, and different methods may be more appropriate for different types of data.
5.2. Molecular Clocks
5.3. Single-Cell Epigenomics
5.4. New Epigenetic Biomarkers
5.5. Consideration of Ageotypes
5.6. Genetic Predisposition to AA
5.7. Application of AA Animal Models
6. Conclusions
- i.
- The concept of an increased rate of age-related changes has certain weaknesses and limitations that are considered in the current review. In particular, so far, no unified methodology and terminology has been established in the field. The studies that justify the AA concept have too low sample sizes. Some age-related changes appear to be reversible under certain conditions.
- ii.
- Aging MBM help to estimate the aging rate increase due to a developed pathology or the exhaustion of individual reserves. A large variety of MBM candidates in different combinations can be associated with the aging brain; however, their validation, clinical interpretation and use in disease subtyping remain a challenge.
- iii.
- Activation of the regenerative mechanisms, and restoring metabolic and energy molecular reserves with novel therapeutic options could be potential ways to decelerate aging in the CNS. For example, sex hormone replacement, antioxidant-based and target therapy, and environmental and lifestyle factors’ improvement may delay ND. Future longitudinal studies could provide clinics and society with more options to prevent AA and slow the aging rate.
7. Afterword: Aging Science History and Theories
Author Contributions
Funding
Conflicts of Interest
Abbreviations
5-mC | 5-methylcytosine |
AA | accelerated aging |
AAG | gene related to accelerated aging |
AD | Alzheimer’s disease |
BA | biological age |
BM | biomarker |
circRNA | circular RNA |
HC | healthy control |
lncRNA | long non-coding RNA |
MBM | molecular biomarkers |
MCI | mild cognitive impairment |
miRNA | microRNA |
ncRNA | non-coding RNA |
ND | neurodegeneration |
NDG | gene that predispose to neurodegeneration |
NV | neurovascular |
NVU | neurovascular unit |
PD | Parkinson’s disease |
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Statsenko, Y.; Kuznetsov, N.V.; Morozova, D.; Liaonchyk, K.; Simiyu, G.L.; Smetanina, D.; Kashapov, A.; Meribout, S.; Gorkom, K.N.-V.; Hamoudi, R.; et al. Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond. Cells 2023, 12, 2451. https://doi.org/10.3390/cells12202451
Statsenko Y, Kuznetsov NV, Morozova D, Liaonchyk K, Simiyu GL, Smetanina D, Kashapov A, Meribout S, Gorkom KN-V, Hamoudi R, et al. Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond. Cells. 2023; 12(20):2451. https://doi.org/10.3390/cells12202451
Chicago/Turabian StyleStatsenko, Yauhen, Nik V. Kuznetsov, Daria Morozova, Katsiaryna Liaonchyk, Gillian Lylian Simiyu, Darya Smetanina, Aidar Kashapov, Sarah Meribout, Klaus Neidl-Van Gorkom, Rifat Hamoudi, and et al. 2023. "Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond" Cells 12, no. 20: 2451. https://doi.org/10.3390/cells12202451