Today, I review, link to, and excerpt from Cell Reports Medicine‘s The multiomics blueprint of the individual with the most extreme lifespan [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Cell Rep Med. 2025 Sep 24:102368. doi: 10.1016/j.xcrm.2025.102368. Online ahead of print.
All that follows is from the above resource.
Abstract
Extreme human lifespan, exemplified by supercentenarians, presents a paradox in understanding aging: despite advanced age, they maintain relatively good health. To investigate this duality, we have performed a high-throughput multiomics study of the world’s oldest living person, interrogating her genome, transcriptome, metabolome, proteome, microbiome, and epigenome, comparing the results with larger matched cohorts. The emerging picture highlights different pathways attributed to each process: the record-breaking advanced age is manifested by telomere attrition, abnormal B cell population, and clonal hematopoiesis, whereas absence of typical age-associated diseases is associated with rare European-population genetic variants, low inflammation levels, a rejuvenated bacteriome, and a younger epigenome. These findings provide a fresh look at human aging biology, suggesting biomarkers for healthy aging, and potential strategies to increase life expectancy. The extrapolation of our results to the general population will require larger cohorts and longitudinal prospective studies to design potential anti-aging interventions.
Keywords: aging; epigenetics; genetics; microbiome; supercentenarian.
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
Introduction
The indexed individual, from now on termed M116, was the world’s oldest verified living person from January 17th, 2023, until her passing on August 19th, 2024, reaching the age of 117 years and 168 days (https://www.grg-supercentenarians.org/wop/). She was a Caucasian woman born on March 4th, 1907, in San Francisco, USA, from Spanish parents and settled in Spain since she was 8. A timeline of her life events and her genealogical tree are shown in Figures S1A and S1B. Although centenarians are becoming more common in the demographics of human populations, the so-called supercentenarians (over 110 years old) are still a rarity. In Catalonia, the historic nation where M116 lived, the life expectancy for women is 86 years, so she exceeded the average by more than 30 years (https://www.idescat.cat). In a similar manner to premature aging syndromes, such as Hutchinson-Gilford Progeria and Werner syndrome, which can provide relevant clues about the mechanisms of aging, the study of supercentenarians might also shed light on the pathways involved in lifespan. To unfold the biological properties exhibited by such a remarkable human being, we developed a comprehensive multiomics analysis of her genomic, transcriptomic, metabolomic, proteomic, microbiomic, and epigenomic landscapes in different tissues, as depicted in Figure 1A, comparing the results with those observed in non-supercentenarian (NSC) populations. The picture that emerges from our study, although derived only from this one exceptional individual, shows that extremely advanced age and poor health are not intrinsically linked and that both processes can be distinguished and dissected at the molecular level.
