Aging neurons hinder neurogenesis in mice

Disrupting senescent cells in the senescent stem cell niche can enhance hippocampal neurogenesis and cognitive function in mice, the researchers report Jan.

Senior author David Kaplan, of the Hospital for Sick Children in Toronto, Canada, said: "Our findings further support the notion that excessive aging is the driving factor behind aging, and that the loss of these cells even in later life enables stem cells to benefit.

Senescent cells, which are permanently suppressed due to chronic stress, are partly responsible for tissue decline during aging

Several studies point to stem cells as targets for aging and aging-related functional decline

"Stem cells exist throughout life and, like us, are damaged by aging, environmental stress and the degradation of the mechanisms that enable them to function optimally," Kaplan explained

In the new study, Kaplan teamed up with SickKids' Freda Miller and Paul Frankland (@franklandlabs) to test the neural stem cell niche within the brains of middle-aged mice.

This sudden burst of neurogenesis had long-term effects in middle-aged mice

These results support the idea that senescence-dependent accumulation of senescent cells, including senescent stem cells in the hippocampal niche, negatively affects normal stem cell function and adult neurogenesis, leading to age-dependent cognitive decline in the hippocampus

"When we improve our surroundings by removing harmful cells in the stem cell niche, we start to mobilize and awaken dormant stem cells so they can generate new spatial learning and memory neurons," Kaplan said

While these findings implicate stem cell senescence in age-related decline, stem cells are clearly not the only important senescent cell matrix in the nervous system

"Furthermore, most research on waking dormant stem cells has focused on mobilizing the cells themselves," Kaplan said

According to the authors, a limitation of one study was the use of middle-aged rather than aged mice, which may be more relevant to potential treatment strategies for cognitive loss in older adults

"One remaining question is whether reducing the number of senescent stem cells alone improves normal stem cell function and cognition, or whether removing other types of senescent cells is also important," Kaplan said

article title

Restoration of hippocampal neural precursor function by ablation of senescent cells in the senescent stem cell niche