Metabolic Signatures of Aging and Gametogenesis in Hydra oligactis

Aging can be experimentally induced in Hydra oligactis, making it an exception among the "immortal" cnidarian genus Hydra. In response to cold temperatures, H. oligactis polyps switch from asexual to "emergency" sexual reproduction and eventually age and die. We used GC-MS-based metabolite profiling to characterize cold-induced (CI) metabolic reprogramming during concurrent sexual differentiation and aging in H. oligactis. Metabolites in four clusters either decreased or increased progressively until week 8, when animals were severely aged, whereas others peaked at sexual maturity after 4-6 weeks. At week 4, signatures of failing cytoprotection and neurotransmitter function appeared in both sexes, including a drastic reduction of taurine, whose deficiency is a known driver of aging in other organisms. Taurine supplementation partly reversed interstitial stem cell loss during the first 2 weeks of cold induction and subsequent sexual differentiation. Metabolites in the NAD⁺ synthesis and salvage pathways, such as picolinate and niacin, also declined. Changes in pyruvate and TCA cycle intermediates indicated increased energy demands associated with both gametogenesis and aging. Urate, the final oxidation product of purine metabolism, showed the highest fold-change, peaking at sexual maturity in both sexes and remaining elevated. The abundance of most purine and pyrimidine bases also increased, in line with nucleotide cleavage by apoptosis, as part of gametogenesis and aging. Sexual maturity was clearly reflected by high levels of polyamines, such as putrescine, cadaverine, and 3-hydroxybutyrate, required for spermatogenesis. Our study reveals metabolic processes related to gametogenesis and aging and highlights differences between female and male metabolism.