Adam Antebi

Max Planck Institute for Biology of Ageing

Prof. Dr. Adam Antebi

Principle Investigator
Director of MPI for Biology of Ageing

+49 0221 379 70 502

aantebi[at]age.mpg.de

Website

AntebiLab

Curriculum Vitae

Research Areas

Molecular Genetics of Ageing

Our lab studies the regulatory processes that govern longevity using the nematode C. elegans,the African killifish N. furzeri, mice and human cells, using a combination of genetics, systems and molecular biology.

Research Focus

Our goal is to understand the various processes that result in the gradual decline of organismal homeostasis and physiological functions during aging, and identify cellular protective mechanisms and regulatory pathways that help prevent ageing and promote longevity.

Over the last several decades, molecular genetic studies in model organisms have identified multiple evolutionarily conserved pathways that regulate longevity, including insulin/IGF, AMPK, and mTOR signaling, mitochondrial function, dietary restriction and signals from the reproductive system. We have elucidated some of the key players and mechanisms that underly these pathways. Our recent work has focused on whether these various pathways converge on shared mechanisms, in order to understand what lies at the heart of longevity and to identify critical therapeutic targets that could extend health and lifespan. Such shared processes include regulation of nucleolar function, one-carbon metabolism, and Mondo-TFEB transcriptional networks.

C. elegans expressing the nucleolar protein fibrillarin (FIB-1) tagged with green fluorescent protein (GFP). FIB-1::GFP allows us to visualize the nucleolus. A group of worms was imaged at 10 x magnification.

Photo of an adult male killifish. Their short lifespan of six to eight months makes them an ideal model for studying the aging process, as well as longevity interventions.

Our Goals

Our current goals focus on very fundamental cellular processes impacting life span.

In particular, the fidelity of information flow from DNA to RNA to protein is crucial to cellular and organismal function. Surprisingly, we found that mild mutations in RNA polymerase II, the enzyme transcribing DNA to RNA, diminish transcriptional speed and extend C. elegans lifespan. Similarly, a mild dysregulation of mRNA splicing factor RNP-6/PUF60 prolongs life. We hypothesize that slowing information flow triggers a specific stress response that is protective and mitigates damage. We now aim to better understand the coupling of information flow, and unravel the mechanism by which specific splicing factors impinge on stress signaling pathways to impact health and longevity from worms to humans.
On the level of information flow to protein, we previously discovered that the nucleolus is a central convergence point of different longevity pathways. This intranuclear organelle is essential for the biogenesis of ribosomes, the molecular machines that carry out protein synthesis. Interestingly, small nucleoli often correlate with longevity in C. elegans, and with metabolic health in humans, while large nucleoli often correlate with senescence. Current work focuses on deciphering regulatory pathways upstream and downstream of the nucleolus responsible for lifespan control.
Fasting/refeeding regimens, like caloric restriction and intermittent fasting, enhance health and lifespan, and can promote tissue regeneration. However, the underlying molecular mechanisms mediating regeneration remain largely elusive. We are investigating both short term fasting/refeeding, as well as long term diapause states in both C. elegans and killifish to identify conserved pathways modulating longevity and rejuvenation. Using molecular genetic and systems approaches, we are identifying the underlying mechanisms and metabolites involved in these processes.
Chronic low-grade inflammation is a key hallmark of aging (inflammaging). We are using killifish to monitor inflammation during aging, and specifically study the involvement of nucleotide sensing pathways of the innate immune system in normative aging, and under conditions of DNA damage.

Key Publications

Ripa, R., Ballhysa, E., Steiner, J.D., Laboy, R., Annibal, A., Hochhard, N., Latza, C., Dolfi, L., Calabrese, C., Meyer, A.M., Polidori, M.C., Müller, R.-U., and Antebi, A. (2023). Refeeding-associated AMPKγ1 complex activity is a hallmark of health and longevity. Nature Aging. 10.1038/s43587-023-00521-y.
Huang, W., Kew, C., Fernandes, S.A., Lohrke, A., Han, L., Demetriades, C., and Antebi, A. (2022). Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity. Nat Aging 2, 796-808. 10.1038/s43587-022-00275-z.
Gerisch, B., Tharyan, R.G., Mak, J., Denzel, S.I., Popkes-van Oepen, T., Henn, N., and Antebi, A. (2020). HLH-30/TFEB Is a Master Regulator of Reproductive Quiescence. Dev Cell 53, 316-329 e315. 10.1016/j.devcel.2020.03.014.
Tharyan, R.G., Annibal, A., Schiffer, I., Laboy, R., Atanassov, I., Weber, A.L., Gerisch, B., and Antebi, A. (2020). NFYB-1 regulates mitochondrial function and longevity via lysosomal prosaposin. Nat Metab 2, 387-396. 10.1038/s42255-020-0200-2.
Tiku, V., Jain, C., Raz, Y., Nakamura, S., Heestand, B., Liu, W., Späth, M., Suchiman, H.E.D., Müller, R.-U., Slagboom, P.E., Partridge, L., and Antebi, A. (2017). Small nucleoli are a cellular hallmark of longevity. Nature communications 8, 16083-16083. 10.1038/ncomms16083.