Wu Group: Laboratory for Ageing Research

Our lab studies the molecular and metabolic mechanisms that underlie biological ageing, with a focus on its impacts on female fertility. A key mechanistic interest for the lab is the role of altered metabolism, including the molecular metabolism of the redox cofactor nicotinamide adenine dinucleotide (NAD+). Our group previously showed that declining levels of this cofactor are a reversible cause of reproductive ageing, a discovery that has resulted in ongoing clinical trial translation. We conduct experiments in C. elegans, mice and humans, with a wide variety of experimental techniques, in particular the use of stable isotope tracing and metabolomics to investigate unexpected aspects of textbook metabolic pathways.

Current projects

The Laboratory for Ageing Research is works on fundamental mechanisms and interventions that could maintain healthy ageing. These have immediate applications in other conditions, including slowing the decline in fertility with age, preventing the long-term adverse effects of chemotherapy treatment, and unexplored aspects of cell biochemistry with age.

The following projects and more are available for study at both the honours and PhD level...

New treatments to maintain female fertility during biological ageing and following chemotherapy treatment
Role of the pentose phosphate pathway and the enzyme glucose-6-phosphate dehydrogenase in reproductive ageing
DNA transposons in genome instability and the regulation of lifespan
New treatments to reduce the side effects of chemotherapy and improve long-term health in cancer survivors
Studies of the metabolism of nicotinamide adenine dinucleotide (NAD⁺)
Understanding the role of somatic-germline interactions in reproductive ageing and lifespan
Tracing NAD+ turnover dynamics in humans
Changes in cellular metabolism during fertilization and embryo development as a treatment for age-related infertility

Highlighted publications

Bertoldo MJ; Listijono DR; Ho WHJ; Riepsamen AH; Goss DM; Richani D; Jin XL; Mahbub S; Campbell JM; Habibalahi A; Loh WGN; Youngson NA; Maniam J; Wong ASA; Selesniemi K; Bustamante S; Li C; Zhao Y; Marinova MB; Kim LJ; Lau L; Wu RM; Mikolaizak AS; Araki T; Le Couteur DG; Turner N; Morris MJ; Walters KA; Goldys E; O'Neill C; Gilchrist RB; Sinclair DA; Homer HA; Wu LE, 2020, 'NAD⁺ Repletion Rescues Female Fertility during Reproductive Aging', Cell Reports, 30, pp. 1670 - 1681.e7, http://dx.doi.org/10.1016/j.celrep.2020.01.058
Kim LJ; Chalmers TJ; Madawala R; Smith GC; Li C; Das A; Poon EWK; Wang J; Tucker SP; Sinclair DA; Quek LE; Wu LE, 2023, 'Host–microbiome interactions in nicotinamide mononucleotide (NMN) deamidation', FEBS Letters, 597, pp. 2196 - 2220, http://dx.doi.org/10.1002/1873-3468.14698
Wu LE; Fiveash CE; Bentley NL; Kang MJ; Govindaraju H; Barbour JA; Wilkins BP; Hancock SE; Madawala R; Das A; Massudi H; Li C; Kim LJ; Wong ASA; Marinova MB; Sultani G; Das A; Youngson NA; Le Couteur DG; Sinclair DA; Turner N, 2023, 'SIRT2 transgenic over-expression does not impact lifespan in mice', Aging Cell, 22, http://dx.doi.org/10.1111/acel.14027 *Corresponding
Aflatounian A; Paris VR; Richani D; Edwards MC; Cochran BJ; Ledger WL; Gilchrist RB; Bertoldo MJ; Wu LE; Walters KA, 2022, 'Declining muscle NAD⁺ in a hyperandrogenism PCOS mouse model: Possible role in metabolic dysregulation', Molecular Metabolism, 65, pp. 101583, http://dx.doi.org/10.1016/j.molmet.2022.101583 *Corresponding
Das A; Huang GX; Bonkowski MS; Longchamp A; Li C; Schultz MB; Kim LJ; Osborne B; Joshi S; Lu Y; Treviño-Villarreal JH; Kang MJ; Hung TT; Lee B; Williams EO; Igarashi M; Mitchell JR; Wu LE; Turner N; Arany Z; Guarente L; Sinclair DA, 2018, 'Impairment of an Endothelial NAD⁺-H2S Signaling Network Is a Reversible Cause of Vascular Aging', Cell, 173, pp. 74 - 89.e20, http://dx.doi.org/10.1016/j.cell.2018.02.008

Our experts

Lindsay Wu

Group Leader

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Lindsay Wu - Group Leader

Lindsay Wu is an American Federation for Aging Research (AFAR) / Hevolution Investigator, leading the Laboratory for Ageing Research at UNSW where his lab studies the molecular mechanisms that cause biological ageing, with a focus on declining female reproduction with age.