2026-03-12 スタンフォード大学
＜関連情報＞
- https://news.stanford.edu/stories/2026/03/architecture-aging-behavior-animals-research
- https://www.science.org/doi/10.1126/science.aea9795
- https://www.nature.com/articles/s43587-024-00692-2
- https://www.cell.com/cell/fulltext/S0092-8674(15)01488-9
生涯にわたる行動スクリーニングにより脊椎動物の老化の構造が明らかに Lifelong behavioral screen reveals an architecture of vertebrate aging
Claire N. Bedbrook, Ravi D. Nath, Libby Zhang, Scott W. Linderman, […] , and Karl Deisseroth
Science Published:12 Mar 2026
Editor’s summary
Continuous recording of a vertebrate’s adult life from adolescence until death would provide a complete view into the behavioral architecture of aging. However, the long time scale and complexity of vertebrate aging have so far precluded such observations. Bedbrook et al. leveraged major advances in machine learning and computer vision to follow nearly every moment of the adult life of a naturally short-lived vertebrate, the African killifish. The authors found that individual animals followed distinct aging trajectories defined by abrupt transitions in behavior. These results might lead to better understanding of the aging process in other vertebrates, including humans. —Mattia Maroso
Structured Abstract
INTRODUCTION
With increased age comes a substantially increased risk of devastating illnesses, including cancers, cardiovascular diseases, and dementias. As elderly populations grow, so does the urgency to better understand the lifelong process of aging. We hypothesized that fundamental insights into the dynamic process of aging could come from continuously observing individuals across life until aging-related death. However, given the long timescale of vertebrate aging, continuous observation across an individual vertebrate animal’s life has not been practical.
RATIONALE
We studied the African turquoise killifish, a vertebrate model for aging with a naturally compressed lifespan (median 4 to 8 months), to continuously record behavior from puberty to death and explore the architecture of adult lifespan progression and aging. Behavior is a rich readout of animal state that integrates diverse features of multiorgan system physiology, including the core nervous system functions of sensation, cognition, and action. We designed an unbiased screen to systematically explore how behavioral patterns change with age and to determine whether behavior could predict future aging differences and even remaining lifespan. This unbiased approach also allowed us to explore the impact of interventions on behavior and to test for the presence of behavioral stages that define progression through adult life.
RESULTS
We built a system to continuously screen behavior across the entire adult lifespan of individual animals, which enabled the initial investigation of vertebrate multidimensional behavioral dynamics spanning timescales from single video frames (tens of milliseconds) to whole lifespans (~250 days from puberty to death) in a systematic and quantitative manner. With this view into the process of aging, we discovered that behavioral trajectories of short-lived animals are distinct from those of long-lived animals. Based on these behavioral trajectories, we separated chronologically age-matched animals predicted to be long- versus short-lived and performed multiorgan transcriptomic profiling. Animals destined for a long lifespan exhibited transcriptomic changes in ribosomal and metabolic pathways but not in other key aging-related pathways such as inflammation. Through our machine-learning models, we found that the behavior of an individual at a relatively young age sufficed to predict future short or long lifespan, and key predictive behaviors appeared to be conserved across the animal kingdom. The noninvasive behavioral screen also enabled the exploration of how a human-relevant longevity intervention (dietary restriction) influences the process of aging. Finally, our continuous tracking of the aging process from adolescence to death revealed the surprising observation that animals exhibit notable transitions between stereotyped behavioral stages at distinct ages. These data suggest a model for the architecture of adult life progression, in which the process of aging encompasses the succession of discrete life stages, rather than a gradual continuous decline.
CONCLUSION
We designed and built a platform to continuously track naturalistic behavior across lifespan from adolescence to death, allowing for a high-resolution unbiased screen of the process of aging in vertebrates. We found that animal behavior can be a highly informative noninvasive readout of the process of aging and that vertebrate animals progress through adulthood in an orderly sequence of stable and stereotyped behavioral stages. The lifespan architecture described here advances basic understanding of biological aging and may also enable targeted mechanistic and therapeutic discovery work that is relevant to human aging and age-related disease.
Lifelong behavioral screen.
To investigate the lifelong progression of aging, we continuously tracked behavior from adolescence to death in the naturally short-lived African turquoise killifish. Naturalistic behavioral readout, which is noninvasive, revealed individual animal aging trajectories across life. Behavior not only can be used to infer age but also can forecast future lifespan. The continuous nature of behavioral tracking suggests an architecture of aging whereby individuals progress through adulthood in an orderly sequence of stable and stereotyped behavioral stages.
Abstract
Mapping behavior of individual vertebrate animals across lifespan could provide an unprecedented view into the lifelong process of aging. We created a platform for high-resolution continuous behavioral tracking of the African killifish across natural lifespan from adolescence to death. We found that animals follow distinct individual aging trajectories. The behaviors of long-lived animals differed markedly from those of short-lived animals, even relatively early in life, and were linked to organ-specific transcriptomic shifts. Machine-learning models accurately inferred age and even forecasted an individual’s future lifespan, given only behavior at a young age. Finally, we found that animals progressed through adulthood in a sequence of stable and stereotyped behavioral stages with abrupt transitions, revealing precise structure for an architecture of aging.
ヒトの加齢過程におけるマルチオミクスプロファイルの非線形ダイナミクス Nonlinear dynamics of multi-omics profiles during human aging
Xiaotao Shen,Chuchu Wang,Xin Zhou,Wenyu Zhou,Daniel Hornburg,Si Wu & Michael P. Snyder
Nature Aging Published:14 August 2024
DOI:https://doi.org/10.1038/s43587-024-00692-2
Abstract
Aging is a complex process associated with nearly all diseases. Understanding the molecular changes underlying aging and identifying therapeutic targets for aging-related diseases are crucial for increasing healthspan. Although many studies have explored linear changes during aging, the prevalence of aging-related diseases and mortality risk accelerates after specific time points, indicating the importance of studying nonlinear molecular changes. In this study, we performed comprehensive multi-omics profiling on a longitudinal human cohort of 108 participants, aged between 25 years and 75 years. The participants resided in California, United States, and were tracked for a median period of 1.7 years, with a maximum follow-up duration of 6.8 years. The analysis revealed consistent nonlinear patterns in molecular markers of aging, with substantial dysregulation occurring at two major periods occurring at approximately 44 years and 60 years of chronological age. Distinct molecules and functional pathways associated with these periods were also identified, such as immune regulation and carbohydrate metabolism that shifted during the 60-year transition and cardiovascular disease, lipid and alcohol metabolism changes at the 40-year transition. Overall, this research demonstrates that functions and risks of aging-related diseases change nonlinearly across the human lifespan and provides insights into the molecular and biological pathways involved in these changes.
アフリカ産ターコイズキリフィッシュのゲノムは、寿命の進化と遺伝的構造に関する洞察を提供する The African Turquoise Killifish Genome Provides Insights into Evolution and Genetic Architecture of Lifespan
Dario Riccardo Valenzano ∙ Bérénice A. Benayoun ∙ Param Priya Singh ∙ … ∙ Andreas Beyer ∙ Eric A. Johnson ∙ Anne Brunet
Cell Published: December 3, 2015
DOI:https://doi.org/10.1016/j.cell.2015.11.008
Highlights
- De novo genome assembly and annotation of the African turquoise killifish
- Key aging genes are under positive selection in the turquoise killifish
- Differences in lifespan between killifish strains are genetically linked to sex
- A resource for comparative genomics and experimental aging studies
Summary
Lifespan is a remarkably diverse trait ranging from a few days to several hundred years in nature, but the mechanisms underlying the evolution of lifespan differences remain elusive. Here we de novo assemble a reference genome for the naturally short-lived African turquoise killifish, providing a unique resource for comparative and experimental genomics. The identification of genes under positive selection in this fish reveals potential candidates to explain its compressed lifespan. Several aging genes are under positive selection in this short-lived fish and long-lived species, raising the intriguing possibility that the same gene could underlie evolution of both compressed and extended lifespans. Comparative genomics and linkage analysis identify candidate genes associated with lifespan differences between various turquoise killifish strains. Remarkably, these genes are clustered on the sex chromosome, suggesting that short lifespan might have co-evolved with sex determination. Our study provides insights into the evolutionary forces that shape lifespan in nature.
