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Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians
Supercentenarians, people who have reached 110 y of age, are a great model of healthy aging. Their characteristics of delayed onset of age-related diseases and compression of morbidity imply that their immune system remains functional. Here we performed single-cell transcriptome analysis of 61,202 peripheral blood mononuclear cells (PBMCs), derived from 7 supercentenarians and 5 younger controls. We identified a marked increase of cytotoxic CD4 T cells (CD4 cytotoxic T lymphocytes [CTLs]) as a signature of supercentenarians. Furthermore, single-cell T cell receptor sequencing of 2 supercentenarians revealed that CD4 CTLs had accumulated through massive clonal expansion, with the most frequent clonotypes accounting for 15 to 35% of the entire CD4 T cell population. The CD4 CTLs exhibited substantial heterogeneity in their degree of cytotoxicity as well as a nearly identical transcriptome to that of CD8 CTLs. This indicates that CD4 CTLs utilize the transcriptional program of the CD8 lineage while retaining CD4 expression. Indeed, CD4 CTLs extracted from supercentenarians produced IFN-γ and TNF-α upon ex vivo stimulation. Our study reveals that supercentenarians have unique characteristics in their circulating lymphocytes, which may represent an essential adaptation to achieve exceptional longevity by sustaining immune responses to infections and diseases.
Journal Article
If I live to be 100 : the wisdom of centenarians
More than fifty extraordinary Americans, who have all celebrated their one hundredth birthday, share a century of insights. Paul Mobley has taken his camera on the road once again, this time to photograph America's oldest and wisest citizens. Mobley traveled to all fifty states to find these indomitable, extraordinary centenarians. In this inspiring collection of intimate and powerful portraits, direct quotes, and personal stories, we learn that wisdom is the reward for perseverance. The centenarians in Mobley's stunning portfolio are eyewitnesses to a century dominated by world wars and conflicts, space travel, and cultural and digital revolutions. Their stories are inspirational, educational, and deeply touching. In them, we are reminded that love, loss, hope, and grief are essential ingredients in a full life and that humor can get us through the worst of times. Mobley's heartfelt portraits are a beautiful tribute to this unique assemblage of Americans. There are more than 70,000 centenarians in the United States alone. Each of them has touched others with their gift of long lives. This book is a celebration of this generation and an inspiration to the rest of us. -- Amazon.com.
BOOK
An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging
While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8-96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The strongest contributor to iAge was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling and poor vascular function. Furthermore, aging endothelial cells in human and mice show loss of function, cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. In conclusion, we identify a key role of CXCL9 in age-related chronic inflammation and derive a metric for multimorbidity that can be utilized for the early detection of age-related clinical phenotypes.
Journal Article
Living beyond age 105: When the improbable becomes reality
Deaths at very advanced ages have increased considerably in the last two decades. The exact number of such deaths documented in the International Database on Longevity IDL is established only after a strict age validation process. The vast majority of people who attain these exceptional ages are women. Supercentenarians (aged 110 or above) are over-represented in Guadeloupe and Martinique.
Journal Article
The 100-year-old man who climbed out the window and disappeared
Confined to a nursing home and about to turn 100, Allan Karlsson, who has a larger-than-life back story as an explosives expert, climbs out the window in his slippers and embarks on an unforgettable adventure involving thugs, a murderous elephant and a very friendly hot dog stand operator.
Book
INTRODUCING CENTENARIAN STUDIES IN AN AGING WORLD
Abstract
Centenarian studies have come of age. With the first comprehensive centenarian studies conducted more than 35 years ago, there are now centenarian databases in the United States, in Europe, and in Asian countries. The major focus of these studies has been on genetic and family longevity factors, on support systems, personality, and on health behaviors. Another emphasis has been on various health components, such as physical health, mental health, frailty, and psychological well-being. In recent years, a second generation of centenarian studies has been initiated, comparing earlier born cohorts with later born cohorts. Among the first studies conducting a cohort comparison, the Danish centenarian studies, the Georgia centenarian studies, and the Tokyo centenarian studies showed inconsistent results. Whereas some studies indicated that later born cohorts enjoyed higher levels of functioning (e.g., Denmark, U.S. Georgia), other studies showed poorer performance (e.g., Japan). The current symposium sheds additional light on cohort comparisons with recently collected data from the second Hong Kong Centenarian Study, the Kyotango centenarian cohort, and the Health and Retirement Study. This presentation summarizes major findings from centenarian studies conducted around the world and highlights activities of the International Consortium of Centenarian Studies (ICC).
Journal Article
The oldest student : how Mary Walker learned to read
\"A picture book biography sharing the inspiring and incredible true story of the nation's oldest student, Mary Walker, who learned to read at the age of 116\"-- Provided by publisher.
Book
Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?
The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro-endocrine-immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.
Journal Article