+1 (629)348-3199Editorial - Journal of Aging and Geriatric Psychiatry (2025) Volume 9, Issue 2
Brain aging: Complex pathways and therapeutic target.
Prof. Akira Tanaka*
Department of Geriatric Psychiatry, University of Tokyo
- *Corresponding Author:
- Prof. Akira Tanaka
Department of Geriatric Psychiatry
University of Tokyo.
E-mail: akira.taaka@tokyo-u.ac.jp
Received : 05-Feb-2025, Manuscript No. AAAGP-25-193; Editor assigned : 07-Feb-2025, PreQC No. AAAGP-25-193(PQ); Reviewed : 27-Feb-2025, QC No AAAGP-25-193; Revised : 10-Mar-2025, Manuscript No. AAAGP-25-193(R); Published : 19-Mar-2025 , DOI : 10.35841/aaagp-9.2.193
Citation: Tanaka PA. Brain aging: Complex pathways and therapeutic target. J Age Geriat Psych. 2025;09(02):193.
Introduction
The current understanding of brain aging emphasizes the critical distinctions between normal aging, mild cognitive impairment, and Alzheimer's disease [1].
This process is far from simple, involving a complex interplay of genetics, individual lifestyle choices, and underlying pathology. The urgent need for more integrated research is clear, aiming to develop targeted interventions that can effectively address the multifaceted challenges of age-related cognitive decline. Neuroinflammation plays a significant role in brain aging, with specific attention directed towards microglial epigenetics [2].
Environmental factors profoundly influence these epigenetic changes, impacting microglial function and contributing to cognitive decline associated with aging. Investigating these molecular pathways offers promising new avenues for understanding and potentially mitigating age-related cognitive impairment, paving the way for novel therapeutic approaches. Cerebral Small Vessel Disease (CSVD) is a major, often overlooked, cause of cognitive decline and stroke within the aging population [3].
A detailed exploration of its underlying mechanisms is vital for comprehending its progression. Ongoing clinical trials are actively discussing and testing potential therapeutic targets and diagnostic improvements, with the hope of developing more effective strategies to combat this debilitating condition. The gut microbiome exerts a profound influence on brain aging and neurodegeneration, establishing a compelling connection often referred to as the gut-brain axis [4].
Compelling evidence supports its crucial role in maintaining cognitive function. Disruptions in the microbial balance, known as dysbiosis, can exacerbate age-related brain changes, thereby presenting potential new therapeutic strategies that focus on modulating the gut environment for brain health. Epigenetic modifications accumulate in the brain as a natural part of the aging process [5].
These modifications include changes in DNA methylation patterns, various histone modifications, and alterations in the expression of non-coding RNAs. Collectively, these molecular changes contribute significantly to age-related shifts in gene expression, which consequently impact neuronal function and increase an individual's susceptibility to neurodegenerative diseases. Vascular aging is intricately linked to cognitive decline, representing a critical area of research [6].
Arterial stiffness, endothelial dysfunction, and other vascular changes are major contributors to brain pathology and subsequent cognitive impairment. Systematic reviews highlight critical gaps in current knowledge and outline future research directions, emphasizing the urgent need for robust intervention strategies targeting vascular health to preserve cognitive function. Sleep plays a pivotal and often underestimated role in maintaining optimal brain health throughout the aging process [7].
Age-related sleep disturbances are not merely inconvenient; they are directly implicated in contributing to cognitive decline and accelerating neurodegenerative processes. This underscores the profound importance of achieving adequate and restorative sleep for preserving cognitive function and overall brain vitality in the elderly. Mitochondrial dysfunction is increasingly recognized as a central player in brain aging [8].
Impaired mitochondrial dynamics, elevated oxidative stress, and disrupted energy metabolism collectively contribute to increased neuronal vulnerability and a decline in cognitive abilities. Exploring therapeutic strategies that specifically target and enhance mitochondrial health holds significant promise for mitigating age-related brain disorders. Synaptic plasticity, particularly within the hippocampus – a brain region fundamentally crucial for memory formation and recall – undergoes significant changes during the aging process [9].
Understanding the molecular and cellular mechanisms that underlie these alterations is key to unraveling their impact on cognitive function. Proposing and developing potential interventions to preserve neuronal flexibility and adaptability in the aging brain remains a critical and active area of scientific inquiry. Blood-brain barrier (BBB) dysfunction is identified as a key contributor to both brain aging and neurodegeneration [10].
The mechanisms by which BBB breakdown leads to neuronal damage and subsequent cognitive decline are being actively investigated. This highlights the BBB's considerable potential as a therapeutic target for developing novel treatments for a wide range of age-related brain disorders and preserving cognitive integrity.
Conclusion
Research into brain aging reveals a multifaceted process involving distinctions between normal aging, mild cognitive impairment, and Alzheimer's disease, influenced by genetics, lifestyle, and pathology. Key mechanisms contributing to age-related cognitive decline include neuroinflammation, particularly through microglial epigenetics influenced by environmental factors. Cerebral small vessel disease is a significant contributor to cognitive decline and stroke, with ongoing research focusing on therapeutic targets and diagnostic improvements. The gut microbiome also profoundly impacts brain aging and neurodegeneration via the gut-brain axis, where microbial dysbiosis can worsen age-related brain changes, suggesting new therapeutic avenues. Epigenetic modifications like DNA methylation, histone changes, and non-coding RNAs accumulate in the brain with age, altering gene expression, impairing neuronal function, and increasing susceptibility to neurodegenerative diseases. Vascular aging, characterized by arterial stiffness and endothelial dysfunction, significantly contributes to brain pathology and cognitive impairment, emphasizing the need for targeted intervention strategies. Sleep plays a critical role in maintaining brain health, as age-related sleep disturbances are linked to cognitive decline and neurodegenerative processes. Mitochondrial dysfunction, involving impaired dynamics, oxidative stress, and energy metabolism, contributes to neuronal vulnerability. Synaptic plasticity in the hippocampus, crucial for memory, undergoes changes during aging, affecting cognitive function. Finally, blood-brain barrier dysfunction is identified as a key contributor to brain aging and neurodegeneration, leading to neuronal damage and cognitive decline, making it a potential therapeutic target. Collectively, these studies underscore the complex biological pathways involved in brain aging and offer diverse targets for interventions to preserve cognitive function.
References
- Ronald CP, Clifford RJJ, Steven TD. The aging brain: What we know and what we need to know.. Alzheimers Dement. 2023;19(8):5693-5705.
Indexed at, Google Scholar, Crossref
- Jessica AB, Rachel RM, Nicholas MT. Neuroinflammation and the aging brain: microglial epigenetics and the environment.. Front Mol Neurosci. 2023;16:1118182.
Indexed at, Google Scholar, Crossref
- Joanna MW, Catharina JMK, Mark EL. Cerebral small vessel disease: from mechanisms to clinical trials.. Lancet Neurol. 2019;18(8):684-696.
Indexed at, Google Scholar, Crossref
- Daniel E, Tobias LMS, Andreas DLB. The gut microbiome and the aging brain: evidence and emerging concepts.. Cell. 2020;183(2):301-316.
Indexed at, Google Scholar, Crossref
- Anne E, Christian HW, Stephanie WR. Epigenetic mechanisms of aging in the brain.. Cell Mol Life Sci. 2020;77(17):3371-3388.
Indexed at, Google Scholar, Crossref
- Meghan EO, Laura JD, Jessica TST. Vascular aging and cognitive decline: a systematic review of current evidence and future directions.. J Am Heart Assoc. 2020;9(14):e016140.
Indexed at, Google Scholar, Crossref
- Bryce AM, William JKM, Jason DKSM. The importance of sleep for the aging brain.. Neurobiol Dis. 2019;129:104611.
Indexed at, Google Scholar, Crossref
- Dae-Kwang K, Seong-Wook L, Jung-Eun K. Mitochondrial dysfunction in the aging brain: a review of current evidence and therapeutic opportunities.. Exp Neurobiol. 2021;30(2):143-157.
Indexed at, Google Scholar, Crossref
- Thomas CF, Rachel ER, Stephanie CW. Synaptic plasticity in the aging brain: insights from the hippocampus.. Front Synaptic Neurosci. 2021;13:644407.
Indexed at, Google Scholar, Crossref
- Axel M, Berislav Z, William BGM. Blood-brain barrier dysfunction in the aging brain: mechanisms and therapeutic implications.. Nat Med. 2020;26(10):1530-1540.