Volume 1 Issue 9, September 2021

A new study shows that increased microRNA-31 expression is associated with hair follicle aging. Genetic deletion of the microRNA or pharmacological inhibition of its downstream effectors suppresses hair follicle stem cell aging in mice.

New research reveals that the mitochondrial citrate carrier is crucial for the accumulation of acetyl-CoA in the cytosol and nucleus, and efficient histone acetylation. Lysosomal degradation of this carrier drives mesenchymal stem cell aging in a process characterized by tightly packed chromatin and reduced expression of osteogenic genes.

The ability to remain true to cellular identity and function is lost during aging and carcinogenesis when DNA damage triggers inflammation that progressively erodes homeostatic cues. Shalabi et al. show that these losses are accelerated in patients with germline cancer mutations in DNA repair genes and are independent of chronological age.

The integrated stress response governs adaptive reprogramming of protein synthesis following external or internal signals. The authors discuss its role in aging and longevity, and highlight strategies to enhance health and resilience.

COVID-19 causes high mortality in older adults compared to younger people. Bartleson et al. review the immunological mechanisms that make older adults vulnerable to COVID-19 and discuss ways to bolster immunity in this population during COVID-19.

In this whole-exome sequencing study of the largest centenarian cohort to date, Lin et al. demonstrate that conserved pathways—for example, IIS and AMPK signaling—are as relevant to human longevity and healthy aging as they are in worms, flies and mice.

Changes in hair and skin can be the most obvious and earliest signs of aging. The authors report that skin and hair follicle stem cell (HFSC) aging is driven by stress-induced upregulation of miR-31, which targets Clock to activate MAPK/ERK and deplete HFSCs via transepidermal elimination. Blocking the pathway with MAPK/ERK inhibitors protects against skin aging.

Aged mesenchymal stem cells exhibit decreased osteogenesis. Pouikli et al. link impaired MSC differentiation to histone hypoacetylation caused by lower mitochondrial acetyl-CoA export due to enhanced lysosomal degradation of the citrate carrier Slc25a1. Restoring histone acetylation to youthful levels rescues osteogenesis.

Transient expression of the pluripotency factors Oct4, Sox2, Klf4 and c-Myc can mitigate the effects of stem cell aging on tissue health. Neumann and colleagues show that Myc expression alone converts aged oligodendrocyte progenitor cells into neonatal-like cells, and is sufficient to enhance central nervous system regeneration in an otherwise aged environment.

Aging is the most important risk factor for breast cancer in women without genetic mutations. Shalabi and colleagues now show that histologically normal mammary epithelial cells genetically predisposed to cancer exhibit features of accelerated aging, such as the loss of cell lineage markers, differentiation defects and transcriptome-wide enrichment of expression of genes related to aging and inflammation.

As part of Myeloid Cells in Neurodegenerative Disease (MyND) initiative, the authors profiled the transcriptome of primary monocytes and microglia from patients with Parkinson’s disease and controls, revealing the pathways and genes that are altered in the immune system of patients with Parkinson’s disease.