What Has Omics Data Taught Us About Dementia?
An enormous amount of biological data can now be obtained from any given study population, and at reasonable cost. The resulting databases have grown to become very large. The epigenome, transcriptome, proteome, metabolome, microbiome, and much more, are at the fingertips of every epidemiological researcher, at multiple time points, before and after interventions, and at different ages. It is easy enough to find differences in the data between more healthy subjects and patients suffering from one or more age-related conditions. It is a harder task to build upon that data in order to find useful therapies. Aging causes sweeping changes in all measures of cellular biochemistry, but few of those changes are connected to good points of intervention. Most are consequences, not causes.
In today's open access paper, the authors discuss this environment of near unlimited biological data in the context of age-related neurodegeneration. Examining the differences characteristic of disease and then laboriously working backwards in search of causes and points of intervention is the polar opposite strategy to that of the SENS vision for rejuvenation, which is to tackle the known root causes of aging and then see what happens as a result. The former involves a great deal more work than the latter before the production of therapies becomes viable.
What we have learned to date from the omics approach to non-Alzheimer's dementias
More than 50 million people live with dementia in worldwide, and due to the rapidly aging population, dementia cases are expected to increase at least five times in 2050. Dementia refers to a clinical syndrome characterized by the deterioration of this memory ability and, progressive cognitive decline that hinders an individual's ability to function. Dementia symptoms are persistent and progressive. Although 60%-70% of dementia cases that develop related are to Alzheimer's disease (AD), the remaining 30%-40% are diagnosed as non-Alzheimer's (non-AD) dementia.
The non-AD pathogenesis is still unknown. Despite advances in modern medicine, the developmental process of dementia is still not fully understood. Although some mechanisms have been defined, they still cannot fully explain the process that develops in all patients. In recent years, new molecular techniques that enable high throughput data to be obtained in laboratories, have created hope for many neurological diseases, such as AD. Thanks to the "omics" concept that has become part of neurological research, these techniques have enabled us to examine the unknown areas of biology, such as the genome, transcriptome, proteome, microbiome, and metabolome, thus providing a new perspective of the interactions between host and microorganisms.
From this point of view, preclinical and clinical data has demonstrated a bidirectional interaction between the host and the microorganism and led to the formation of the term "gut-brain axis" between the gastrointestinal system and the brain. This interaction is very important for the regulation of the neural, hormonal, and immunological balance of human beings. Our gut is therefore named our second brain. Indeed, based on this concept, new relationships between the gut microbiome and dementia have been identified. Alterations in the composition of the gut microbiome have also been shown to independently cause an increase in risk of dementia, along with other traditional risk factors.
The presence of microbiome-associated metabolites and bacterial products in the systemic circulation may increase, especially with the inflammatory process that can lead to dementia. Despite this information, it is not yet known how changes in the gut microbiome and microbiota-related metabolites affect cognitive functions. Confusion due to conflicting findings regarding this relationship between the gut microbiome and dementia also exist. Understanding this bidirectional interaction is essential for discovering the underlying molecular pathogenic mechanisms of many disorders, especially in the neuroscience field. Studies in this field will provide the means to develop personalized treatments and will reveal different biomarkers and help us consider new treatment options. This review highlights the progress that has been made in omics research while noting the gaps in our knowledge.