Perspectives

The advent of plaque-clearing antibodies to the amyloid-β as the first disease-modifying treatment for Alzheimer’s disease will change the course of this disease, the most common type of dementia. Related progress will gradually alter the trajectory of human aging.

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.

To build health equity for an aging world, research at the intersections of biology, toxicology and the social and behavioral sciences points the way: to promote healthy aging, focus on the environment.

Cognitive frailty (CF) is the complex and intertwined co-occurrence of physical frailty and cognitive decline. Untangling the interplay between these two domains and correctly diagnosing CF in the clinic is vital for early diagnosis and intervention.

Aging is associated with a variety of changes; however, which of the observed changes drive aging is incompletely understood. In this Perspective, the authors discuss cellular senescence, epigenetics and stem cell alterations with this question in mind.

High-throughput analysis of cellular landscapes is an important tool to decipher the molecular mechanisms driving aging and disease. Here, Singh and Benayoun discuss key considerations in the design and analysis of omic data to gain robust and reproducible insights into the aging process.

This Perspective describes the clinical relevance of animal models in dementia for translational research. The authors emphasize incorporating aging as a component in model organisms to understand its contribution to disease pathogenesis.

This Perspective outlines a strategy to move towards a future with personalized medicine for Alzheimer’s disease by empowering patients in orchestrating diagnosis, prediction and prevention of the onset of dementia.

In this Perspective, the authors discuss experimental scenarios that breach the assumption of independence of all samples or participants in a study, specifically in aging research. They outline various strategies to improve the rigor and accuracy of the science with design and analysis solutions, while also considering real-world constraints.

This Perspective lays out the impetus and goals of the Cellular Senescence Network established to comprehensively identify and characterize senescent cells (SnCs) across tissues and lifespan, providing a publicly available SnC atlas.

In this Perspective, Jan Vijg and Brandon Milholland discuss that at high ages the probability of survival becomes vanishingly small, presenting a soft limit to human lifespan. They elaborate on the mechanistic basis of the observed limit to maximum human lifespan, and on the seemingly impossible future developments required to circumvent the current limit.

Carol Brayne and Terrie Moffit discuss the limitations of large-scale volunteer databanks (LSVD) for understanding aging and disease, call for further evaluation of their value and offer their thoughts on how to make the reporting of LSVD studies more transparent.

This Perspective describes the blueprint, challenges and potential solutions for the transformation of Alzheimer’s disease clinical care pathway with biomarker-guided and digitally facilitated detection and intervention at early disease stages.

The authors discuss how adopting a complex systems perspective is a crucial step in advancing our understanding of the aging process and requires fundamental alteration of the questions being asked and the methods used to answer them.

Whether and how cognitive training may be used to improve cognitive functions in older age remains incompletely explored, and existing studies have yielded inconsistent results. Here, the authors argue that emerging technologies can transform the field of cognitive enhancement by enabling personalized strategies for cognitive enhancement in older adults.

Suicide is an important problem among older adults and in particular older men. Here, the author discusses factors that impact suicide risk, including social determinants of health and cultural perception of old age, and proposes strategies for a multifaceted approach to suicide prevention.

Age-friendly cities initiatives aim to facilitate active and healthy aging. Focusing on the urban physical environment, the authors argue that longevity-ready cities that aim for better health and well-being for people of all ages from a life-course perspective can accomplish more than initiatives focused solely on old age.

The integrated stress response governs adaptive reprogramming of protein synthesis following external or internal signals. The authors discuss its role in aging and longevity, and highlight strategies to enhance health and resilience.

This Perspective discusses the socioeconomic concept of the longevity dividend, in which healthy and productive aging is achieved through a positive correlation between three dimensions: life expectancy, health and the economy.