Human Hippocampal Neurogenesis Persists throughout Aging

Abstract

SUMMARY Adult hippocampal neurogenesis declines in aging rodents and primates. Aging humans are thought to exhibit waning neurogenesis and exercise-induced angiogenesis, with a resulting volumetric decrease in the neurogenic hippocampal dentate gyrus (DG) region, although concurrent changes in these parameters are not well studied. Here we assessed whole-autopsy hippocampi from healthy human individuals ranging from 14 to 79 years of age. We found similar numbers of intermediate neural progenitors and thousands of immature neurons in the DG, comparable numbers of glia and mature granule neurons, and equivalent DG volume across ages. Nevertheless, older individuals have less angiogenesis and neuroplasticity and a smaller quiescent progenitor pool in anterior-mid DG, with no changes in posterior DG. Thus, healthy older subjects without cognitive impairment, neuropsychiatric disease, or treatment display preserved neurogenesis. It is possible that ongoing hippocampal neurogenesis sustains human-specific cognitive function throughout life and that declines may be linked to compromised cognitive-emotional resilience.

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…Age‐related decline of cognitive function is associated with decreased numbers of neural stem cells (Fan, Wheatley, & Villeda, 2017). However, recent two researches (Boldrini et al, 2018; Sorrells et al, 2018) are contradictory to each other on whether endogenous neurogenesis exists in adult human hippocampus and new techniques need to be developed to track the newly generated neurons. Stem cell‐based therapeutics, both exogenous (transplantation) and endogenous (via factors such as growth factors that stimulate stem cells), could have important implications for both aging and AD (Limke & Rao, 2002).…”

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression

“…Most of the post-mortem studies have now evidenced that in adult humans, new neurons continued to be generated with a modest decline during aging (Eriksson et al 1998; Reif et al 2006; Spalding et al 2013). Although recently questioned by Sorrells et al (2018) who suggested that human neuroplasticity could differ from other species, it has been nevertheless confirmed that in human DG, about 700 new neurons were generated per day whatever the age (Boldrini et al 2018). …”

The α7 nicotinic acetylcholine receptors regulate hippocampal adult-neurogenesis in a sexually dimorphic fashion

“…NSCs are usually quiescent, while immature granule cells differ from sparsely activated (Chawla et al 2005; Jung and McNaughton 1993) mature granule cells by responding to the normally inhibitory neurotransmitter GABA with excitation, and being prone to long-term potentiation (Esposito et al 2005; Ge et al 2007; Schmidt-Hieber et al 2004). Despite some controversy (Sorrells et al 2018), most data agree that adult neurogenesis occurs at a rate of 1.75% per year in humans (Spalding et al 2013) and persists through aging (Boldrini et al 2018), and can be modified by environmental factors such as exercise (van Praag et al 1999) and social isolation (Holmes 2016). NSCs can be induced to differentiate through excitation (Deisseroth et al 2004), but activated neurons may differentiate into astrocytes, leading to decreases in the NSC pool and a loss of neurogenic potential (Encinas et al 2011).…”