⌛ Aging healthily: the secret might be in our skin

What if, long before the first signs of frailty appear, our cells carried clues about how we would age?

Through the analysis of skin cells, fibroblasts, from biopsies performed on participants of the Inspire-T cohort, researchers from Inserm, the University of Toulouse, CNRS, the French Blood Establishment (EFS) [1], in collaboration with IHU HealthAge, have discovered that these cells provide valuable clues about individuals' overall health status. Their work shows that certain biological markers indicating the proper functioning of fibroblasts could help detect and anticipate signs of frailty or decline in physical and mental capacities, regardless of people's age.

Their results, published in Aging Cell, open perspectives in personalized preventive medicine to support healthier aging.


While aging represents a major societal challenge, health research has long focused on biological markers related to chronological age, often disconnecting them from individuals' overall or functional health status [2].

To better understand the role of cellular aging in the overall aging process, fibroblasts present themselves as a privileged study target. Present throughout the body's tissues, they are found in the skin dermis where they play an essential structural role by secreting the extracellular matrix - a network of proteins that supports tissues and allows resident cells to perform their functions. Fibroblasts are also involved in skin regeneration and healing as well as in its immunity. Easily accessible through simple skin biopsies, they constitute valuable models for identifying new biological markers related to aging.

A team of researchers, led by Isabelle Ader, Inserm researcher, and Louis Casteilla, professor at the University of Toulouse, at the Geroscience and Rejuvenation Research Center - RESTORE (Inserm/University of Toulouse/CNRS/EFS) and in collaboration with IHU Health Age, thus became interested in how fibroblasts could provide information about health status during aging, through the identification of specific biological markers.

Their study was based on the analysis of fibroblasts taken from skin biopsies performed on 133 women and men aged 20 to 96 years, presenting varied health profiles. These participants, included in the French Inspire-T cohort (see box), were classified as more or less frail or robust depending on their age and relative health status.

The scientists subjected these fibroblasts to different stress factors mimicking those encountered during life (metabolic, infectious stresses, chemotherapy...). They then evaluated their overall functionality through three of their main functions: structural, immune/inflammatory and metabolic. The objective was to identify biological markers associated with the general and functional health status of the donors, in connection with the different stages of aging.

Two markers of functional health status caught the team's attention: fibroblasts from pre-frail or frail individuals showed reduced activity of their mitochondria - the "powerhouses" of cells. These cells also secreted less periostin, an extracellular matrix protein. The decrease in the latter was also observed in people with low intrinsic capacity, an indicator of unfavorable aging and poorer overall health status.

"These two biological markers, related to the metabolic and structural functionality of fibroblasts and independent of chronological age or sex, appear as indicators of an individual's cellular frailty, even when fibroblasts are cultured in the laboratory after biopsy, indicates Isabelle Ader. In this, they reflect what could be described as a "health memory" at the cellular level and present interesting potential for the early detection of frailty and poor health before any clinical sign", adds the researcher.

Periostin also appears for the first time as a key biological marker associated with intrinsic capacity as defined by the WHO, and thus as a potential indicator of individuals' functional health.

These results highlight the reliable signals that our body's cells could provide about an individual's overall health status.

"Our work opens concrete perspectives in the early detection of signs of frailty or decline in physical and cognitive capacities in preventive medicine", adds Isabelle Ader. "Early identification of alterations in cellular health could enable the development of targeted personalized medicine strategies to better preserve functional health and prolong autonomy throughout life", concludes the researcher.

This work is the subject of a patent filed with Inserm Transfert in 2024.

Notes:

[1] Also in collaboration with teams from INRAE and Columbia University in New York.

[2] Functional health corresponds to a person's ability to perform daily activities while maintaining their health and well-being. It depends on two variables: the living environment and intrinsic capacity, a concept developed by the WHO that designates all the physical and mental capacities specific to the person, independent of their environment. A decrease in the intrinsic capacity score is associated with impaired overall health, which can lead to loss of autonomy and dependence.