NEW YORK – By bringing together multiomic data for young, middle-aged, and elderly women, a team from the Chinese Academy of Sciences and other centers in China have developed more than a dozen "aging clocks" reflecting the process of aging in specific tissues or body parts, molecular systems, the immune system, and the whole body.
As they reported in Med on Friday, the team used RNA sequencing, mass spectrometry, and 16S rRNA gene sequencing to track transcriptomic, proteomic, metabolomic, and gut microbiome patterns in plasma, peripheral blood mononuclear cell, or stool samples from 113 healthy female participants from China, who ranged in age from 20 to 66 years. The investigators also turned to single-cell RNA sequencing to assess transcriptome profiles in samples from a subset of 12 individuals.
"We found several reported biomarkers of aging in this study," senior and co-corresponding author Guang-Hui Liu, a stem cell and regeneration researcher at the Chinese Academy of Sciences and president of the Chinese Society of Aging Cell Research, explained in an email.
Together with physical, functional, and behavioral measurements, the omics data made it possible to put together a series of aging clocks based on single-layered or composite data, including specific tissue aging clocks and clocks for everything from facial or phenotypic aging to protein, transcript, metabolite, hormone, lipid, or immune system aging.
"In total, we built 14 distinct aging clocks," Liu said. "These aging clocks can act as an integrated estimator of biological age and be utilized to monitor aging trajectory and to evaluate aging intervention strategies."
From the transcriptomic data, for example, the investigators highlighted age-related changes in immune cell representation, including a decline in naïve T cell levels and an uptick in the prevalence of cytotoxic T cells, Liu noted. Their results also revealed distinct immune cell combinations or immunotypes in the young, middle-age, or elderly participants profiled.
On the other hand, the protein profiles pointed to increasing levels of known aging biomarkers such as C-reactive protein (CRP) or GPNMB protein in the older individuals, the team reported, along with enhanced blood plasma levels of apolipoproteins and inflammatory proteins in aging participants.
With these analyses, the team identified pathways that appeared to be particularly important at different stages of life, including processes showing enhanced activity in women in their 30s and in their 50s.
For example, the clocks pointed to age-related contributions of processes such as lipid metabolism, chronic inflammation, hormone dysregulation, and tissue degeneration. In particular, the analyses suggested that "elevated inflammation and perturbed hormone metabolism might contribute to the decline of tissue fitness," Liu noted.
From these and other findings, the investigators speculated that some aging effects might be boosted or staved off by altered hormone levels — a notion backed up by the reduced rate of biological aging detected with the aging clock models in individuals receiving hormone replacement therapy.
"In line with this hypothesis, we did find high correlation between [a hormone-focused aging clock known as] hormoneAge and the other aging clocks," Liu said. "More importantly, individuals receiving hormone replacement therapy (HRT) exhibit a slower aging pace of multiple aging clocks compared to the age-matched individuals without HRT."