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Profiling and understanding plasma proteomes could unlock Longevity

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There’s no place like plasma proteomics when it comes to understanding biological processes and discovering biomarkers as two recent papers show.

Proteins are the building blocks of life; gather a group of proteins together in a certain space and you have a proteome. A proteome usually means all the proteins expressed and functioning in a certain space, whether that’s a single cell, a whole organ system or a volume of bodily fluid.

Longevity.Technology: Used in both clinical practice and laboratory testing, blood tests are the most common type of biological tests. Blood comes into contact with all tissues and cells, collecting substances that have been synthesised, secreted, degraded or absorbed all round the body and plasma is its greatest constituent. Understanding the profile of a plasma proteome creates a picture of protein expression in health and disease and the entire pathophysiological status of a living organism, leading to advances in disease diagnosis and therapeutic monitoring.

Proteomics is available to consumers too; UK start-up AgeCurve can generate deep age profiles by sequencing and quantifying thousands of human proteins to assess different aspects of the ongoing biological aging process – and all from a saliva sample. This is a case of direct-to-consumer personal proteomics.

The field of plasma proteomics has evolved to detect and analyse even proteins that are present at extremely low concentrations in plasma. This coupled with the amount of the pathophysiological information it contains make the plasma proteome the ultimate target for biomarker discovery.

Two papers published in Aging Cell detailed research that used the SomaScan® assay, a platform that uses proprietary protein-binding reagents to generate deep, broad and accurate measurements of the protein landscape in a blood sample.

The first paper, Plasma proteomic profile of age, health span, and all-cause mortality in older adults, looked at an older cohort (1,025 participants, aged 65–95) to see which proteins were associated with chronological age. The researchers found clusters of highly correlated proteins that were “significantly associated with chronological age and demonstrated that the biology of aging overlapped with complex age-associated diseases and other age-related traits [1].”

Dr Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine

The research team’s pathway analysis showed that inflammatory response, organismal injury and abnormalities, cell and organismal survival and death pathways were all associated with aging. The study also made new associations between several proteins and aging and the researchers were able to construct: “A proteomic age model that predicted mortality, and suggested possible proteomic signatures possessed by a cohort enriched for familial exceptional longevity [1].”

We spoke to Dr Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine and co-author on both papers.

“It is important that biomarkers will distinguish biological age from chronological age,” Dr Barzilai told Longevity.Technology. “If you take a test when you are 50 years old, but biologically you are only 40, you may not need a colonoscopy! It is even more important because biomarkers change with gerotherapeutics, so we know a therapy works as soon as possible without spending lots of resources. Proteomes like those in these papers reflect tissue breakdown are likely to change with any therapy, so they are great biomarkers to understand.”

The development of a proteomic age model is an exciting move; distinguishing the differences between biological and chronological age and predicting lifespan could be important clinical tools to extend both lifespan and healthspan.

In the second paper, Plasma proteomic profile of frailty, the authors sought to “decipher the proteomic signature of frailty [2]” and examine the biological manifestation of frailty through protein expression, which they thought might be regulated at genetic, transcriptional and epigenetic levels.

 


 

“The biomarkers will change with gerotherapeutics, so we know if it work as soon as possible without spending lots of resources. Proteomes like those in these papers reflect tissue breakdown are likely to change with any therapy, so they are great biomarkers to understand.”

 


 

Frailty is a complex condition particularly common among the elderly, who also suffer from increased vulnerability to adverse outcomes. It is caused by decreased physiological reserve and dysfunction in numerous biological systems and is characterised by unintentional weight loss, fatigue, and physical and cognitive impairments.

The study identified a number of proteins that were positive as well as negatively associated with the clinical frailty phenotype, as well as proteins that point towards a role for the lipid metabolism pathway in frailty. The researchers were able to confirm this by the pathway analysis.

 

[1] https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13250
[2] https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13193

Eleanor Garth
Deputy Editor Now a science and medicine journalist, Eleanor worked as a consultant for university spin-out companies and provided research support at Imperial College London and various London hospitals in a former life.
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