Volume 3 Issue 12, December 2023

China faces urgent challenges associated with population aging. In this Comment, we summarize China’s adoption of long-term care insurance and underscore its importance for social and economic wellbeing. We provide recommendations for a future of sustainable and healthy aging in China.

Targeting tau in addition to amyloid-β could be the next phase of disease modification in Alzheimer’s disease. The TANGO trial of gosuranemab, which binds the tau N terminus, affected neither clinical outcomes nor brain levels of aggregated tau. The results highlight the importance and challenge of reducing aggregated tau.

On 22 March 2023, the Geroscience Translational Research & International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met in Toulouse, France to discuss avenues to foster the development of intrinsic capacity and frailty clinical trials under a geroscience perspective. A synthesis of these discussions and a set of recommendations are presented in this Meeting Report.

Senescent cells in the brain contribute to age-related neurodegeneration. Analysis of SARS-CoV-2 infection in human brain organoids, animals and post-mortem brain samples from patients with COVID-19 reveals virus-induced senescence. Pharmacological senolytic treatment following SARS-CoV-2 infection improves COVID-19 neuropathology and could help to protect people from long COVID.

Intrinsic capacity (IC) — a metric that reflects the composite of a person’s physical and mental capacities — varies across adulthood and between individuals of the same age. People with an IC below the tenth percentile suffer from a high burden of diseases, frailty, disabilities and recent falls.

In vivo reprogramming by expression of the transcription factors OCT4, SOX2, KLF4, and MYC (OSKM factors) has been associated with early mortality and cancer. We report that these adverse effects are associated with liver and intestinal dysfunction. Strategic control of OSKM expression in these organs through a newly developed transgenic mouse model reduced adverse effects. Our model yields valuable insights into the potential of in vivo reprogramming for rejuvenation and regeneration.

This Perspective describes and discusses the Information Theory of Aging, which proposes that aging primarily stems from the loss of youthful epigenetic information that can be restored via epigenetic reprogramming to heal injury and reverse aging.

Preclinical models are central to aging research. Yet, these models often lack key features of female humans. Here, the authors discuss shortcomings in the study of female aging and share opportunities for closing the gap in our understanding of sex-dependent aging trajectories.

Partial reprogramming to enhance regeneration and mitigate age-related phenotypes is limited by toxicity. Parras et al. report a transgenic reprogrammable mouse strain with attenuated toxicity, by avoiding OSKM expression in the liver and intestine.

There is scant evidence for how intrinsic capacity (IC), the combination of an individual’s physical and mental capacities, varies throughout adulthood. In this study, the authors demonstrated a method to establish IC reference centile curves using data of individuals aged 20–102 years from the French INSPIRE-T cohort.

Chamoli et al. identified MIC, a benzocoumarin molecule, that promotes longevity in C. elegans by inducing mitophagy via DAF-12/FXR and HLH-30/TFEB, and they demonstrate a conserved MIC efficacy in mammalian cells, indicating potential broader relevance.

Age impacts the effect of dietary health and longevity interventions but the underlying mechanisms are incompletely understood. Here the authors study fasting in killifish and find that older animals exhibit a metabolic shift resembling a fasting-like program, which is counteracted by boosting the activity of AMPKγ1, promoting health and longevity.

Aguado et al. show that SARS-CoV-2 induces senescence in human brain organoids and in the brains of COVID-19-infected mice and humans. They demonstrate the therapeutic potential of senolytic therapy in protection against COVID-19-induced brain aging.

Aging is associated with increased atherosclerosis risk and a changing immune landscape. In this study, the authors examined T cell changes in atherosclerotic plaques in mice with age and report an accumulation of clonally expanded effector and memory CD8⁺ T cells, including Gzmk⁺CD8⁺ T cells, which have cytotoxic transcriptomic signatures.

The authors present the results of a phase 2 study of gosuranemab, a monoclonal antibody targeting N-terminal tau, in patients with early Alzheimer’s disease. Gosuranemab was safe and well tolerated, but the clinical efficacy endpoint was not met.