OVER DEZE AFLEVERING
xercise in a Pill? How Muscle Could Protect Memory, with Professor Constanza J Cortes
Episode Summary
Could your body get some of the benefits of a workout without you doing the exercise? And could a drug like that help prevent memory loss or treat Alzheimer’s?
Host Daphna Stern speaks with Professor Constanza J Cortes, a neuroscientist at the University of Southern California, about how exercise could help preserve memory as we age. Professor Cortes’ goal is to develop treatments for people who cannot exercise enough because of pain, illness or limited mobility.
Her research starts with muscle. During exercise, muscles release chemical messengers that travel around the body, including to the brain. Professor Cortes is testing whether a drug, sometimes described as an exercise mimetic, could reproduce some of those signals without the need to exercise. Her team has already improved memory and other brain outcomes in mouse models of Alzheimer’s by changing what happens in their muscles.
But her latest research also raises an important question: does a brain affected by Alzheimer’s still respond to exercise in the same way as a healthy brain? In mouse studies, exercise triggered some of the expected molecular changes but did not lead to the same improvements in memory or broader protection of the brain.
We discuss how much of exercise a drug could realistically reproduce, whether healthy people could benefit, what still needs testing in humans, differences between how male and female muscle responds to exercise, and her ambition to have a treatment in the clinic within 10 years.
About the Guest
Professor Constanza J Cortes is an Assistant Professor of Gerontology at the University of Southern California and leads the Cortes Lab at the USC Leonard Davis School of Gerontology. Her research focuses on exercise, brain ageing, Alzheimer’s disease and the signals that pass between skeletal muscle and the brain.
She is principal investigator of a National Institute on Aging-funded research programme investigating exercise-associated signalling against brain ageing and Alzheimer’s disease. Her work also examines sex differences in how the body responds to exercise. In 2026, she received the Women in AGE Scientific Achievement Award in recognition of her contributions to ageing research.
Research Mentioned in This Episode
Skeletal muscle TFEB signalling promotes central nervous system function and reduces neuroinflammation during ageing and neurodegenerative disease
Cell Reports, 2023
Research showing how activating TFEB in skeletal muscle can reproduce some effects associated with exercise and influence the ageing brain.
https://pubmed.ncbi.nlm.nih.gov/37952157/
Activation of the muscle-to-brain axis ameliorates neurocognitive deficits in an Alzheimer’s disease mouse model via enhancing neurotrophic and synaptic signalling
2024
Research identifying prosaposin (PSAP) as part of the muscle-to-brain signalling pathway and examining PS18 as a potential way to reproduce some of its effects.
https://pubmed.ncbi.nlm.nih.gov/39269584/
Long-term voluntary exercise reveals limited translation of hippocampal molecular responses into neuroprotection in 5xFAD mice
bioRxiv preprint, 2026
Research examining why an Alzheimer’s disease brain may respond differently to prolonged exercise, despite showing some molecular signs of an exercise response.
https://pubmed.ncbi.nlm.nih.gov/42817989/
Single-nuclei RNA-sequencing uncovers sexually divergent exercise signatures partially mimicked by TFEB overexpression in mouse skeletal muscle
bioRxiv preprint, 2026
Research showing substantial differences between male and female skeletal muscle responses to exercise and TFEB activation.
https://pubmed.ncbi.nlm.nih.gov/41659513/
Further Reading
National Geographic: Why exercise can help keep the brain healthy
https://www.nationalgeographic.com/magazine/article/new-clues-are-revealing-why-exercise-can-keep-the-brain-healthy
USC Leonard Davis School of Gerontology: Professor Cortes on understanding the effects of exercise on the brain
https://gero.usc.edu/2023/04/13/assistant-professor-constanza-cortes-understanding-the-effects-of-exercise-on-the-brain
USC: Constanza Cortes receives the 2026 Women in AGE Scientific Achievement Award
https://gero.usc.edu/2026/10/01/constanza-cortes-phd-receives-women-in-age-scientific-achievement-award
The Cortes Lab at USC
https://gero.usc.edu/labs/corteslab
Timestamps
* 00:00 Introduction and episode overview
* 01:37 Welcome and Professor Cortes’s background
* 02:30 Why the ageing brain became her focus
* 03:58 Does exercise work differently in the ageing brain?
* 05:39 How does muscle communicate with the brain?
* 07:22 What do muscles tell the brain when you run?
* 09:35 Can muscle signals released during exercise improve memory?
* 11:28 Could PS18 mimic exercise’s effects on the brain?
* 12:25 The ongoing study in ageing mice
* 14:25 What is PSAP, and what does it normally do in the body?
* 16:03 Does the PSAP in blood really come from muscle?
* 17:56 What changes inside muscle when we exercise?
* 20:22 Which benefit of exercise would she most want to turn into a treatment?
* 22:04 Could an exercise mimetic prevent Alzheimer’s or treat it?
* 23:19 Could a healthy person benefit?
* 25:05 Can changing muscle protect the brain in Alzheimer’s?
* 27:21 Why running did not rescue memory in Alzheimer’s mice
* 29:07 Can the diseased brain still hear the signal?
* 30:01 Do fewer Alzheimer’s plaques necessarily mean better memory?
* 31:29 What can people with Alzheimer’s do today?
* 32:36 What needs proving before human studies
* 33:47 How much does AI help her research?
* 37:32 What the first human study needs to show
* 39:19 When the biomarkers improve but the person does not feel better
* 43:10 When could an exercise pill reach the market?
* 44:22 What “exercise in a pill” really means
* 46:23 Concerns about off-label use
* 48:08 The unanswered question: sex differences in exercise
* 50:20 Where will the research be in 10 years?
* 51:58 Rapid-fire questions
* 53:16 Closing thoughts
