If we want to make progress against aging and age-related disease, we should define what these are.
There is considerable debate around defining aging. A 2018 review paper notes, "Nowadays one of the most crucial questions of the biological aging research is to determine what is aging per se" [1].
One way to define aging is lifespan and death rates by age. One main reason aging can be terrible is that your risk of death grows exponentially.
This figure, based on mortality data of Japanese women, shows that your likelihood of death increases exponentially with age [2]. Thus, one way to define aging is lifespan and death rates by age. Progress would mean increased lifespan and decreased death rates by age.
But what are the diseases associated with death? We can look at CDC-reported causes of death.![]()
This table shows the top 15 CDC-reported causes of death in 2019 [3]. Most of these are related to age (heart disease, cancer, Alzheimer's, diabetes, etc), but also have major lifestyle components (e.g. diet, exercise, smoking). Progress would be mitigating these diseases.
What are the causes of these diseases? There are "hallmarks of aging" that attempt to provide molecular/cellular of the aging diseases we experience [4]. These include "genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication." Progress would be keeping the hallmarks of aging in more youthful states.
Where should researchers focus? Increasing overall lifespan? Addressing age-related causes of death? Working on hallmarks of aging? Any single disease or aging hallmarks are enough to make a long scientific career. For example, Judy Campisi has made critical progress in understanding cellular senescence (one of the nine listed hallmarks of aging) over a multi-decade career.
My approach is first, to maintain a north star of the impact I want to have, which is increasing average healthy lifespan for humanity. Next, I am trying to be open and interdisciplinary. I try to read widely across hallmarks of aging, biochemistry, aging disease, etc. I will certainly end up focusing somewhere (I am surrounded by world-class neuroscientists at UCSF...). But I don't need to do that yet.
References
[1] Vijg, Campisi and Lithgow. Molecular and Cellular Biology of Aging. The Gerontological Society of America. 2015. ISBN 978-0-929596-04-4
[2] "Deaths: Final Data for 2019." Center for Disease Control (CDC). National Vital
Statistics Reports, Volume 70, Number 8. July, 2021. Retrieved online at https://www.cdc.gov/nchs/data/nvsr/nvsr70/nvsr70-08-508.pdf.
[3] Lopez-Otin, et al. The Hallmarks of Aging. Cell, Volume 153, Issue 6, 6 June 2013, Pages 1194-1217. DOI: https://doi.org/10.1016/j.cell.2013.05.039
[4] Fulop, et al. The integration of inflammaging in age-related diseases. Seminars in Immunology, Volume 40, December 2018, Pages 17-35. DOI: https://doi.org/10.1016/j.smim.2018.09.003
