Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity

Abstract

The biomechanical properties of extracellular matrices (ECM) and their consequences for cellular homeostasis have recently emerged as a driver of aging. Here we review the age-dependent deterioration of ECM in the context of our current understanding of the aging processes. We discuss the reciprocal interactions of longevity interventions with ECM remodeling. And the relevance of ECM dynamics captured by the matrisome and the matreotypes associated with health, disease, and longevity. Furthermore, we highlight that many established longevity compounds promote ECM homeostasis. A large body of evidence for the ECM to qualify as a hallmark of aging is emerging, and the data in invertebrates is promising. However, direct experimental proof that activating ECM homeostasis is sufficient to slow aging in mammals is lacking. We conclude that further research is required and anticipate that a conceptual framework for ECM biomechanics and homeostasis will provide new strategies to promote health during aging.

Age-Invariant Genes: Multi-Tissue Identification and Characterization of Murine Reference Genes

“…Our results suggest that these three are the most vulnerable to aging as not many genes related to these hallmarks resist age-related change. In agreement with this finding, these hallmarks are key targets across many existing longevity interventions, i.e., epigenetic reprogramming, senolytics, and enhancing extracellular matrix homeostasis [60–62]. Considering that age-invariant genes tend to be essential for life, one hypothesis is that early changes in these hallmarks may not be particularly detrimental for the organism and thus lack the selective pressure to evolve stability mechanisms in aging.…”

Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation

“…Decades of rigorous research have significantly enhanced our understanding of their pathophysiology. Recent reviews have summarized advances in the dynamics of the extracellular matrix and the regulation of intracellular transcription factors [ 129 , 130 ]. A growing body of research has shifted focus toward the role of neuroinflammation, providing novel insights that could potentially impede or inhibit the progression of such age-related brain disorders [ 131 , 132 ].…”

Strengths and opportunities in research into extracellular matrix ageing: A consultation with the ECMage research community

“…Whilst it is known that models of accelerated ageing show a dysfunctional ECM and a ‘younger ECM’ can rejuvenate old cells, limited research has been done to show that ECM‐based interventions can influence the rate of intrinsic aging. [ 9 ] Thus, there is critical need to expand our knowledge in this area.…”