Today we discuss our partnership with the National Institutes of Health (@NIH) and several other collaborators to expand the frontiers of connectomics by mapping a small fraction (2-3%) of the mouse brain over the next five years. Learn more at: https://t.co/W3s9TcoTqkpic.twitter.com/cb9Lhf4TTo

— Google AI (@GoogleAI) September 26, 2023

Aging is a progressive multifaceted functional decline of a biological system. Chronic age-related conditions such as neurodegenerative diseases are leading causes of death worldwide, and they are becoming a pressing problem for our society. To address this global challenge, there is a need for novel, safe, and effective rejuvenation therapies aimed at reversing age-related phenotypes and improving human health. With gene expression being a key determinant of cell identity and function, and in light of recent studies reporting rejuvenation effects through genetic perturbations, we propose an age reversal strategy focused on reprogramming the cell transcriptome to a youthful state. To this end, we suggest using transcriptomic data from primary human cells to predict rejuvenation targets and develop high-throughput aging assays, which can be used in large perturbation screens. We propose neural cells as particularly relevant targets for rejuvenation due to substantial impact of neurodegeneration on human frailty. Of all cell types in the brain, we argue that glutamatergic neurons, neuronal stem cells, and oligodendrocytes represent the most impactful and tractable targets. Lastly, we provide experimental designs for anti-aging reprogramming screens that will likely enable the development of neuronal age reversal therapies, which hold promise for dramatically improving human health.

Genes encode proteins that are critical for the development and regulation of neural circuits involved in various aspects of brain function such as emotion, thought, learning, and neurological disease. We would like to understand the manner in which proteins responsible for neuronal activities are related to mental processes or brain diseases. Molecular genetics provides the means to determine the genes involved in a particular function of the brain. The human genome project has revealed that a human cell has approximately 30,000–60,000 genes. Neurons differ from other types of cells because they express a set of genes that is specific to them. Neurons are estimated to express ∼ 40% of their total genes, some of which are also expressed in other types of cells. Neuron-specific genes encode neuropeptides, enzymes involved in the synthesis of neurotransmitters (NT), ion channels and receptors, synaptic proteins, and neurotrophic receptors. However, genes expressed in other cell types, such as those encoding protein kinases, cytoskeletal proteins, growth factors, etc., collaborate with neuron-specific genes and are thus involved in neuron-specific behavior such as axon guidance, synaptic plasticity, and neuronal cell death. In this chapter, we examine the basic structure of neurons and discuss genes and proteins that play a key role in neuronal functions. Although complex functions of the brain are determined by the pattern of neuronal connectivity and probably by the number of neurons, it is important to understand the molecular machinery of neurons and synapses given that genetic defects are known to cause many neurological disorders. In addition, remarkable progress has been made to develop drugs that target specific molecules or genes involved in neuronal functions. 

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— the Open Band (Berkeley) (@TheOpenBand) September 28, 2023