Loss of Neurogenesis in Aging Hydra

Abstract

In Hydra the nervous system is composed of neurons and mechanosensory cells that differentiate from interstitial stem cells (ISCs), which also provide gland cells and germ cells. The adult nervous system is actively maintained through continuous de novo neurogenesis that occurs at two distinct paces, slow in intact animals and fast in regenerating ones. Surprisingly Hydra vulgaris survive the elimination of cycling interstitial cells and the subsequent loss of neurogenesis if force‐fed. By contrast, H. oligactis animals exposed to cold temperature undergo gametogenesis and a concomitant progressive loss of neurogenesis. In the cold‐sensitive strain Ho_CS, this loss irreversibly leads to aging and animal death. Within four weeks, Ho_CS animals lose their contractility, feeding response, and reaction to light. Meanwhile, two positive regulators of neurogenesis, the homeoprotein prdl‐a and the neuropeptide Hym‐355, are no longer expressed, while the “old” RFamide‐expressing neurons persist. A comparative transcriptomic analysis performed in cold‐sensitive and cold‐resistant strains confirms the downregulation of classical neuronal markers during aging but also shows the upregulation of putative regulators of neurotransmission and neurogenesis such as AHR, FGFR, FoxJ3, Fral2, Jagged, Meis1, Notch, Otx1, and TCF15. The switch of Fral2 expression from neurons to germ cells suggests that in aging animals, the neurogenic program active in ISCs is re‐routed to germ cells, preventing de novo neurogenesis and impacting animal survival.

Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra

“…Within 1 month, Ho_CS animals lost the ability to regenerate (Fig. 1F,G) and showed behavioral defects (Tomczyk et al, 2019) and aging became irreversible (Fig. S1F-N).…”

“…By contrast, another Hydra species named H. oligactis (Ho) undergoes aging when the temperature drops to 10°C, a condition that induces gametogenesis, budding arrest and progressive animal degeneration (Brien, 1953;Littlefield et al, 1991;Yoshida et al, 2006). The massive production of gametes is accompanied by the loss of somatic interstitial cells, cytoskeleton disorganization, decline in body movements and feeding behavior (Yoshida et al, 2006;Tomczyk et al, 2015Tomczyk et al, , 2019. Sexual animals from male and female Ho strains die within 4 months, showing Gompertzian mortality dynamics normally associated with aging (Finch, 1990) whereas Ho animals maintained at 18°C exhibit no signs of aging.…”

Phenotypic plasticity rather than genotype drives reproductive choices in Hydra populations

“…For instance, in the freshwater cnidarian Hydra oligactis , asexual individuals can be maintained in the laboratory for years without age‐specific increases in mortality or declines in fecundity (Brien, 1953; Martínez et al, 2010; Tomczyk et al, 2015). However, switching from asexual to sexual reproduction results in a senescence‐like process that consists of depletion of adult stem cells, loss of regeneration ability and neurogenesis, decrease in body size, and ultimately an increased rate of mortality (Brien, 1953; Sebestyén et al, 2018; Tomczyk et al, 2017, 2019; Yoshida et al, 2006).…”

Nontraditional systems in aging research: an update

“…Another feature of Ho-CS H. oligactis is a progressive loss of neurogenesis, which is another harbinger of their inevitable aging and death. Mechanistically, this deterioration of the neural system may be associated with the downregulation of two proneurogenic agents, the homeoprotein prdl-a and the neuropeptide Hym-355 [ 69 ].…”