Longevity Papers

Loss of immune cell identity with age inferred from large atlases of single cell transcriptomes.

Erin Connolly, Tony Pan, Maneesha Aluru ... · Transcriptome · Center for Integrative Genomics, and School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA. · pubmed

By analyzing two large atlases of almost 4 million cells, we show that immune-senescence involves a gradual loss of cellular identity, reflecting increased cellular heterogeneity, for effector, and cytotoxic immune cells. The effects are largely similar in both males and females and were robustly reproduced in two atlases, one assembled from 35 diverse studies including 678 adults, the other the OneK1K study of 982 adults. Since the mean transcriptional differences among cell-types remain constant across age deciles, there is little evidence for the alternative mechanism of convergence of cell-type identity. Key pathways promoting activation and stemness are down-regulated in aged T cells, while CD8 TEM and CD4 CTLs exhibited elevated inflammatory, and cytotoxicity in older individuals. Elevated inflammatory signaling pathways, such as MAPK and TNF-alpha signaling via NF-kB, also occur across all aged immune cells, particularly amongst effector immune cells. This finding of lost transcriptional identity with age carries several implications, spanning from a fundamental biological understanding of aging mechanisms to clinical perspectives on the efficacy of immunomodulation in elderly people.

Longevity Relevance Analysis (5)

The paper addresses the loss of immune cell identity with age, which is a fundamental aspect of aging mechanisms. By analyzing large datasets, it provides insights into immune senescence and its implications for aging, making it relevant to longevity research. The findings contribute important knowledge about the biological processes underlying aging and potential clinical implications for immunomodulation in the elderly, thus advancing the field. However, while the findings are significant, they do not represent a major breakthrough, hence the score of 5.

DNA methylation in mammalian development and disease.

Zachary D Smith, Sara Hetzel, Alexander Meissner · DNA Methylation · Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA. z.smith@yale.edu. · pubmed

The DNA methylation field has matured from a phase of discovery and genomic characterization to one seeking deeper functional understanding of how this modification contributes to development, ageing and disease. In particular, the past decade has seen many exciting mechanistic discoveries that have substantially expanded our appreciation for how this generic, evolutionarily ancient modification can be incorporated into robust epigenetic codes. Here, we summarize the current understanding of the distinct DNA methylation landscapes that emerge over the mammalian lifespan and discuss how they interact with other regulatory layers to support diverse genomic functions. We then review the rising interest in alternative patterns found during senescence and the somatic transition to cancer. Alongside advancements in single-cell and long-read sequencing technologies, the collective insights made across these fields offer new opportunities to connect the biochemical and genetic features of DNA methylation to cell physiology, developmental potential and phenotype.

Longevity Relevance Analysis (5)

The paper discusses DNA methylation in the context of mammalian development and disease, particularly focusing on how these modifications relate to aging and the transition to cancer. It explores the functional understanding of DNA methylation and its implications for cell physiology and developmental potential, which are relevant to the root causes of aging. However, while it presents important findings, it does not propose novel solutions or significant breakthroughs that could transform the field, thus receiving a moderate impact score.