Tissue Homeostasis Restored in Response to Chemotoxicity and Aging

(Stem Cells News image)

The accumulation of irreparable cellular damage restricts healthspan after acute stress or natural aging.

Senescent cells are thought to impair tissue function, and their genetic clearance can delay features of aging.

Identifying how senescent cells avoid apoptosis allows for the prospective design of anti-senescence compounds to address whether homeostasis can also be restored.

Here, we identify FOXO4 as a pivot in senescent cell viability. We designed a FOXO4 peptide that perturbs the FOXO4 interaction with p53.

In senescent cells, this selectively causes p53 nuclear exclusion and cell-intrinsic apoptosis.

Under conditions where it was well tolerated in vivo, this FOXO4 peptide neutralized doxorubicin-induced chemotoxicity.

Moreover, it restored fitness, fur density, and renal function in both fast aging XpdTTD/TTD and naturally aged mice.

Thus, therapeutic targeting of senescent cells is feasible under conditions where loss of health has already occurred, and in doing so tissue homeostasis can effectively be restored.

(read more)

One thought on “Tissue Homeostasis Restored in Response to Chemotoxicity and Aging”

  1. Just wondering if there were any testing places in Florida that wanted volunteers for stem cell research.

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