Table 4.

Summary: Open questions in the field.

Research question		Figure
1	Does regional vulnerability to normal ageing determine region-specific susceptibility in neurodegenerative disease?	1
2	Do mechanisms of ageing at the nervous system tissue, cellular and molecular level determine regional vulnerability to both normal ageing and neurodegenerative disease?	2
3	Can differential ageing conceptually extend across scales, from the individual to subcellular level?	3
4	Are the initial sites affected by neurodegenerative pathology also those that are most prone to ageing?	–
5	Can the concept of regional susceptibility to ageing be extended across other age-related diseases, such as cardiovascular disease?	–
6	Is it experimentally tractable to directly compare the ageing status of single cells, cellular subregions, or individual organelles within cells?	–
7	How can an understanding of region-specific vulnerability to ageing and disease be used to guide therapeutic advance e.g. ASO delivery, cellular implantation?	–