Gravitational lensing and integrated stress response: Science Podcast explores the Hubble tension and memory restoration

The Science Podcast for April 2, 2026 presents two threads of modern science: a cosmology-focused exploration of a third route to the Hubble constant using gravitational lensing, and a neuroscience investigation into the integrated stress response ISR and its potential as a therapeutic target for cognitive disorders. In the cosmology segment, Daniel Cleary explains how standard candles and the cosmic microwave background lead to discordant values of the expansion rate, and how gravitational lensing time delays offer an independent distance measurement that could illuminate dark energy. In the neuroscience segment, Mauro Costa Mattioli describes how hyperactivation of ISR in mouse models impairs memory and how a viral protein can suppress ISR to restore memory performance. The discussion highlights exciting avenues for science and the need for further validation in humans.

Overview: two fronts in modern science

The podcast for April 2, 2026 brings together two distinct but equally important threads. In the first, the host and Daniel Cleary of Science discuss the long-standing disagreement in the measured rate of cosmic expansion, the Hubble constant. In the second, Ella Fedder and neuroscientist Mauro Costa Mattioli explore how the integrated stress response (ISR) governs protein synthesis in stressed brain cells and what happens when that pathway remains active. The episode foregrounds how independent methods—gravitational lensing for cosmology and ISR modulation for neuroscience—offer potential leverage on stubborn problems, while underscoring the need for replicable, cross-domain research.

Section 1 — The Hubble tension and a third route: gravitational lensing

The cosmology discussion revisits the classic distance ladder—Cepheid variables and Type Ia supernovae—and contrasts it with the early-universe inference from the cosmic microwave background (CMB). The dialogue emphasizes the current tension: locally inferred H0 values near 73 km s^-1 Mpc^-1 versus CMB-derived values around 67 km s^-1 Mpc^-1, with shrinking error bars but no resolution. A third method leveraging gravitational lensing time delays is introduced. The concept is that light from a distant event, such as a supernova, can take multiple paths around an intervening massive object, arriving at different times and positions. By measuring these delays, along with the lens’s mass distribution and sky geometry, one can infer the distance and H0 in a way independent of standard candles or CMB theory.

"you can use that to triangulate back to where the supernova came from and calculate its distance" - Daniel Cleary

Section 2 — How lensing translates to a cosmological measure

The episode details how time delays depend on the geometry of the lens system and general-relativistic time dilation, with longer light paths and strong gravity producing measurable delays that can anchor distance estimates. The conversation notes that only a handful of such lensed supernovae have been used to constrain H0 so far, but upcoming surveys like the Vera Rubin Observatory in Chile are projected to dramatically increase the sample. The goal is to converge on a robust H0 value that can adjudicate whether the tension points to new physics in cosmology or unrecognized systematics in distance measurements. The potential payoff includes tighter constraints on dark energy and the expansion history of the universe.

"time delays between images give you a handle on the distance to that distant object" - Daniel Cleary

Section 3 — Implications and future directions

The program closes the cosmology thread by outlining how gravitational-lensing measurements, if refined, could tip the balance toward or away from the CMB- or standard-candle-based values, helping identify where the problem lies. The conversation also touches on dark energy, the cosmological constant, and how improved H0 measurements might illuminate the physics of cosmic acceleration. The episode then transitions to the ISR discussion, signaling a shift from the cosmos to the brain, where a different kind of tension—memory decline linked to cellular stress—receives attention.

Section 4 — Integrated stress response and memory in mouse models

The ISR segment introduces a cellular pathway that reduces general protein synthesis during stress while boosting select recovery factors, a mechanism proposed to be critical for memory formation and maintenance. Costa Mattioli explains that mutations in PPP1R15B can hyperactivate ISR, correlating with cognitive impairments and microcephaly, observed in both patients and mouse models. In mice engineered to mimic these mutations, memory formation is impaired and long-term memory is compromised, reflecting the human condition. The researchers then activate a viral protein that suppresses ISR, effectively reawakening protein synthesis and restoring memory-related synaptic plasticity after a single intracranial administration in aged or disease-model mice.

The integrated stress response basically does this for cells. It dials down most protein synthesis, but boosts some key proteins needed for recovery" - Mauro Costa Mattioli

The discussion highlights how memory tasks that couple context with aversive experiences reveal deficits in the ISR-activated brain, and how pharmacological or gene-therapy-like approaches could offer therapeutic avenues for disorders associated with cognitive decline, including Down syndrome and Alzheimer's disease. The speakers emphasize that the ISR-based strategy is not disease-specific but targets a shared cellular vulnerability across diverse cognitive disorders, though they caution that translating findings from mice to humans will require careful validation and safety considerations. The segment concludes with a tempered but enthusiastic outlook on ISR inhibitors and their potential to improve memory by restoring protein synthesis and synaptic strength, while acknowledging that more work is needed to establish clinical impact and timing for treatment in humans.

"this viral protein... is incredibly effective at suppressing the integrated stress response" - Mauro Costa Mattioli

"they perform very similar to normal mice" - Mauro Costa Mattioli

"time will tell how impactful this can be in cognitive disorders" - Mauro Costa Mattioli