Major progress has recently been made in understanding the aging process at the molecular, cellular, and organ system levels. This knowledge is now being applied in preventative and interventional health care. Moreover, because of the severe burden of age-related diseases on societies governments are increasingly developing strategies to extend health span throughout their populations. In this episode Professor Brian Kennedy at the National University of Singapore provides a broad perspective on the field of aging research and its translation into actionable countermeasures. He talks about emerging research on ‘metabolic aging clocks’ and their applications to personalized anti-aging strategies. His experiences in Singapore are particularly enlightening.

LINKS

Professor Kennedy’s NUS profile:

https://medicine.nus.edu.sg/bch/faculty/brian-kennedy/

Related articles:

https://www.sciencedirect.com/science/article/pii/S1568163724004355?via%3Dihub

https://www-sciencedirect-com.proxy1.library.jhu.edu/science/article/pii/S1550413124004534

https://pmc.ncbi.nlm.nih.gov/articles/PMC11330810/pdf/fnagi-16-1428244.pdf

https://pubmed.ncbi.nlm.nih.gov/40250404/

Remarkable progress has been made towards understanding of the molecular control of neurotransmitter release from presynaptic axon terminals and the responses of the postsynaptic neuron by neurotransmitters. We know that synaptic activity is required for learning and memory but the structural basis of a memory (an engram) remains unknown. Anton Maximov has made major contributions to understanding the molecular control of synaptic plasticity associated with learning and memory. Here he talks about his research career journey which began in St. Petersburg Russia followed by postdoc training in Dallas Texas and then to the Scripps Research Institute where he is currently a professor and chair of the Neuroscience Department. He and his team and collaborators recently published an elegant technologically-demanding study in Science in which nanoscale resolution ultrastructural analyses was combined with molecular tagging of neurons encoding a memory revealing an increase in synaptic complexity with intriguing presynaptic structural remodeling.

LINKS

Anton Maximov Lab page: https://www.maximovlab.org/

Science article

https://www-science-org.proxy1.library.jhu.edu/doi/epdf/10.1126/science.ado8316

Structural diversity of chemical synapses:

https://www.cell.com/action/showPdf?pii=S2211-1247%2821%2900267-9

Experience dependent neuron remodeling

https://www.cell.com/action/showPdf?pii=S0896-6273%2814%2900800-9

The outer membrane of cells is comprised of a lipid bilayer consisting of phospholipids, cholesterol, arachidonic acid, omega-3 fatty acids, and others. Embedded in the membrane are various proteins that play roles critical to the survival and function of the cell. Examples of membrane proteins of particular importance for neurons are: ion channels and ion ‘pumps which control neuron excitability; glucose and ketone transporters which are critical for energy metabolism, and receptors for a myriad of neurotransmitters, neurotrophic factors, and other inter-cellular signaling molecules. In this episode chemistry Professor Allan Butterfield talks about research showing a pivotal role for free radicals generated by the Alzheimer’s amyloid-peptide in triggering a chain reaction attack on membrane arachidonic acid resulting in the release of a toxic lipid fragment called 4-hydroxynonenal (HNE). HNE can bind irreversibly to certain amino acids on proteins (lysine, cysteine, histidine) thereby compromising the normal function of the protein. The Butterfield lab and my lab showed that binding of HNE to ion pump proteins, glucose transporters, and glutamate transporters renders neurons vulnerable to excitotoxicity in Alzheimer’s disease. Interventions that suppress membrane lipid peroxidation or detoxify HNE may prevent or ameliorate Alzheimer’s disease and other neurodegenerative disorders.

LINKS

Professor Butterfield’s webpage:

https://chem.as.uky.edu/users/dabcns

Review articles

https://journals.physiology.org/doi/full/10.1152/physrev.00030.2022

https://pmc.ncbi.nlm.nih.gov/articles/PMC7502429/pdf/nihms-1583713.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC7085980/pdf/nihms-1566301.pdf