Dr. Victoria Acosta-Rodriguez (Leader of the Circadian Biology of Aging Unit at the National Institute on Aging (NIA), USA) talks about her research on longevity and caloric restriction. In this first part, Victoria introduces us to longevity research: what kind of interventions and drugs are known to promote longevity and why precise terminology separating life- and healthspan is important. We discuss how the lifespan of mice relates to the lifespan of humans and to what degree we can therefore translate mice studies to the human setting. As we will learn, one intervention to promote longevity is caloric restriction, that is why Victoria also summarizes our current understanding of caloric restriction and defines its different forms.

Chapters:

(00:00:45) Podcast name and host updates

(00:02:51) Introducing Victoria Acosta-Rodriguez

(00:04:43) Interview start

(00:05:26) Victoria’s personal background

(00:09:04) Terminology: Lifespan vs. healthspan

(00:12:25) What interventions promote longevity?

(00:17:24) Defining caloric restriction

(00:21:57) Relevance of feeding time for mice

(00:30:12) Mice vs. humans for longevity studies

(00:38:25) Changes in circadian rhythms upon aging?

(00:44:26) Outro

Main study that we will discuss in depth:

Acosta-Rodriguez, V., Rijo-Ferreira, F., Izumo, M., Xu, P., Wight-Carter, M., Green, C.B., and Takahashi, J.S. (2022). Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice. Science 376, 1192-1202. 10.1126/science.abk0297.

Additional papers that Victoria refers to:

Mice - time-restricted feeding, regular chow

Damiola, F., Le Minh, N., Preitner, N., Kornmann, B., Fleury-Olela, F., and Schibler, U. (2000). Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14, 2950-2961.

Mice - on a high-fat diet & time-restricted feeding

Kohsaka, A., Laposky, A.D., Ramsey, K.M., Estrada, C., Joshu, C., Kobayashi, Y., Turek, F.W., and Bass, J. (2007). High-fat dietcdisrupts behavioral and molecular circadian rhythms in mice. Cell Metab 6, 414-421. 10.1016/j.cmet.2007.09.006.

Arble, D.M., Bass, J., Laposky, A.D., Vitaterna, M.H., and Turek, F.W. (2009). Circadian timing of food intake contributes to weight gain. Obesity (Silver Spring) 17, 2100-2102. 10.1038/oby.2009.264.

Vollmers, C., Gill, S., DiTacchio, L., Pulivarthy, S.R., Le, H.D., and Panda, S. (2009). Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proc Natl Acad Sci U S A 106, 21453-21458. 10.1073/pnas.0909591106.

Hatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E.A., Gill, S., Leblanc, M., Chaix, A., Joens, M., Fitzpatrick, J.A., et al. (2012). Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab 15, 848-860. 10.1016/j.cmet.2012.04.019.

Mice -Calories, Fasting & important variables influencing Lifespan

Mitchell, S.J., Bernier, M., Mattison, J.A., Aon, M.A., Kaiser, T.A., Anson, R.M., Ikeno, Y., Anderson, R.M., Ingram, D.K., and de Cabo, R. (2019). Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories. Cell Metab 29, 221-228 e223. 10.1016/j.cmet.2018.08.011.

Mitchell, S.J., Madrigal-Matute, J., Scheibye-Knudsen, M., Fang, E., Aon, M., Gonzalez-Reyes, J.A., Cortassa, S., Kaushik, S., Gonzalez-Freire, M., Patel, B., et al. (2016). Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. Cell Metab 23, 1093-1112. 10.1016/j.cmet.2016.05.027.

Acosta-Rodriguez, V.A., de Groot, M.H.M., Rijo-Ferreira, F., Green, C.B., and Takahashi, J.S. (2017). Mice under Caloric Restriction Self-Impose a Temporal Restriction of Food Intake as Revealed by an Automated Feeder System. Cell Metab 26, 267-277 e262. 10.1016/j.cmet.2017.06.007.

Acosta-Rodriguez, V.A., Rijo-Ferreira, F., Green, C.B., and Takahashi, J.S. (2021). Importance of circadian timing for aging and longevity. Nat Commun 12, 2862. 10.1038/s41467-021-22922-6.