Nonlinear Aging in Humans, with Transition Points of Increased Risk
This is not the only study to show evidence for points of transition in the progression of degenerative aging. You might recall a study of the gut microbiome published a few years ago that identified a transition into a less beneficial balance of microbial populations taking place in the mid-30s. Here, the points of rapid transition in omics data are identified as mid-40s and 60. This sort of data is interesting, but it should be replicated in larger populations before we get too fired about about interpreting it or speculating about the arrangement of mechanisms driving large and rapid shifts in metabolism at certain ages.
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 metabolism, 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.
Most definitely non linear - from Nature Medicine 5/12/2019
Undulating changes in human plasma proteome profiles across the lifespan
Benoit Lehallier, David Gate, Nicholas Schaum, Tibor Nanasi, Song Eun Lee, Hanadie Yousef, Patricia Moran Losada, Daniela Berdnik, Andreas Keller, Joe Verghese, Sanish Sathyan, Claudio Franceschi, Sofiya Milman, Nir Barzilai & Tony Wyss-Coray
Nature Medicine volume 25, pages1843-1850 (2019)Cite this article
Abstract
Aging is a predominant risk factor for several chronic diseases that limit healthspan1. Mechanisms of aging are thus increasingly recognized as potential therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues2,3,4,5,6,7,8,9,10, which supports a hypothesis that age-related molecular changes in blood could provide new insights into age-related disease biology. We measured 2,925 plasma proteins from 4,263 young adults to nonagenarians (18-95 years old) and developed a new bioinformatics approach that uncovered marked non-linear alterations in the human plasma proteome with age. Waves of changes in the proteome in the fourth, seventh and eighth decades of life reflected distinct biological pathways and revealed differential associations with the genome and proteome of age-related diseases and phenotypic traits. This new approach to the study of aging led to the identification of unexpected signatures and pathways that might offer potential targets for age-related diseases.
I am very surprised and concernd that any research with such a low number of participants, 108 (!), is considered generally relevant, even more that the paper appeared in a renowned journal!