The testis, with the highest number of transcriptionally active genes among human tissues, offers a unique window into how aging affects complex gene regulation. Recent advancements in single-cell RNA sequencing have enabled multi-species studies of aging-related transcriptome changes in testes. However, a comprehensive aging-related cross-species platform for analyzing testicular single-cell transcriptomes remains absent. To address this gap, we developed Aging-TCA (Aging-related Testicular Cell Atlas, available at http://tca.xielab.tech/)— a comprehensive online platform containing aging-related testicular single cell and spatial transcriptome profiles from human, cynomolgus monkey, mouse, and zebrafish across 89 samples and over 460, 000 testicular cells, nuclei or spots. Aging-TCA provides versatile tools for temporal and spatial analyzing testicular aging, including aging-related testicular gene expression visualization, cell-cell communication comparisons, cell-trajectory analysis, gene regulatory network analysis, testicular cell type auto-identification, time-series analysis, and spatial transcriptome comparisons. In summary, we provide a novel platform Aging-TCA for advancing cross-species research into testicular aging, facilitating future investigations in this field.

Aging is a complex process resulting in a decline in organ function. Here the authors proposes that chronic activation of tissue damage response mechanisms drives aging, with aged organs displaying features similar to those seen after acute injury. This provides a unifying framework for understanding the aging process and suggests new directions for treating age-related diseases.

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The evolutionary biology of aging is fundamental to understanding the mechanisms of aging and how to develop anti-aging treatments. Thus far most evolutionary theory concerns the genetics of aging wit...

Tests on Maria Branyas Morera, who was world’s oldest person before she died aged 117, gave doctors a trove of discoveries

Background Aging is characterized by the decline in biological functions, accompanied by changes in gene-to-gene transcriptional coordination, which can be estimated by expression coordination in gene transcriptional network. Notably, gene networks and coordinated expression relationships (CERs) showed inter-individual variability, while personalized aging-related gene expression coordination dynamics in human cohorts have yet to be investigated. Methods In this study, we constructed 15,933 personalized transcriptional networks across 26 tissues from 967 donors aged 20 to 80 years old, using the sample-specific network (SSN) framework based on data from the Gene-Tissue Expression (GTEx) project. Results We identified gene–gene CERs and characterized their age-dependent dynamic trends across tissues, observing a universal trend of increased gene-to-gene coordination loss during aging across tissues. The count of lost CERs is also positively correlated with individual-level aging and senescence-related molecular phenotypes. Notably, we revealed that the lost CERs have potential as biomarkers for individual aging and health status. In addition, we identified gene coordination loss events exhibiting significant positive correlation with age, defined as aging-related lost relationships (ARLRs), which may be functionally associated with pathways related to proteolytic processes. Finally, we showed that ARLRs may contribute to deleterious effects and increased pathogenicity through gene dosage imbalances. Conclusions This study establishes, for the first time, a connection between the loss of gene-to-gene expression coordination and individual-level aging progress. It provides proof-of-principle evidence for using lost gene coordinated expression relationships as biomarkers of healthy aging and highlights the potential risks associated with coordination loss in specific biological pathways during aging.

Mice bred in 2021 were tested by the Interventions Testing Program (ITP) for possible lifespan benefits of 2BAct (2BA), dichloroacetate (DCA), Epicatechin (EPI), Forskolin (FSK), Halofuginone (HAL) and Mitoglitazone (MIT). All agents were administered in the diet ad libitum beginning at 7 months of age. In male mice, EPI increased median lifespan by ~ 5%, and HAL and MIT each increased median lifespan by ~ 9%. EPI and HAL, but not MIT, increased 90% survival. In addition to adding 3 new agents to the list of interventions identified by the ITP that extend lifespan, this report continues the strong male bias in the efficacy of life-extending drugs identified so far.

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that high...

Nature Aging - Are we getting closer to understanding why we age?

Under stress, adults of one jellyfish species revert to the post-larval stage to avoid aging and death.

The macro-experiences of aging are the result of an accumulation of micro-changes that occur over time.

In this Review, Easwaran and Weeraratna outline how ageing leads to epigenetic alterations in the tissue microenvironment, enhancing clonal expansion of mutations and ultimately increasing cancer risk...

It is easier for young animals to regenerate damaged or missing tissues. In this Viewpoint, we propose that this is, in part, attributed to epigenetic changes, with chromatin becoming more closed and...

He’s done the calculations.

A recent publication presented the results of a survey given to longevity experts that attended the 2022 Systems Aging Gordon Research Conference. Corroborating results from a prior survey and broader...

Identifying interventions that reproducibly extend lifespan is a central aim in geroscience, with hopes of translating these findings to enhance the h…

In this Perspective, de Magalhães explores the evolutionary relationship between cancer and ageing, proposing that the need to minimize cancer risk early in life may contribute to tissue degeneration ...

The question of how individual age influences demographic transition rates, such as survival probabilities and reproduction rates, has long been a main question for demographers and evolutionary ecolo...

Nature Reviews Cancer, Published online: 26 August 2025; doi:10.1038/s41568-025-00861-4In this Perspective, de Magalhães explores the evolutionary relationship between cancer and ageing, proposing that the need to minimize cancer risk early in life may contribute to tissue degeneration later on, representing a trade-off that constrains the evolution of longer lifespans.