Cell, volume 186, issue 13, pages 2929-2949.e20
Distinct longevity mechanisms across and within species and their association with aging
Tyshkovskiy Alexander
1, 2
,
Ma Siming
2
,
Shindyapina Anastasia V.
2
,
Tikhonov Stanislav
1
,
Lee Sang-Goo
2
,
Bozaykut Perinur
2, 3
,
Castro José
2, 4, 5
,
Seluanov Andrei
6
,
Schork Nicholas J.
7
,
Gorbunova Vera
6
,
G. F. Ulmishek, R. R. Charpentier, Richard H.
8
,
Gladyshev Vadim N.
2, 9
1
2
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
|
4
I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
|
5
Aging and Aneuploidy Laboratory, IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal
|
6
Departments of Biology and Medicine, University of Rochester, Rochester, NY, USA
|
7
Quantitative Medicine and Systems Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA
|
8
Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI 48109, USA
|
9
Broad institute, Cambridge, MA, USA
|
Publication type: Journal Article
Publication date: 2023-06-03
General Biochemistry, Genetics and Molecular Biology
Abstract
•Distinct molecular mechanisms control lifespan within and across species •Aging effects are reversed by longevity interventions but not by species longevity •Regulation of Igf1 and mitochondrial translation are shared signatures of longevity •Longevity signatures enable the discovery of geroprotectors, such as KU0063794 Lifespan varies within and across species, but the general principles of its control remain unclear. Here, we conducted multi-tissue RNA-seq analyses across 41 mammalian species, identifying longevity signatures and examining their relationship with transcriptomic biomarkers of aging and established lifespan-extending interventions. An integrative analysis uncovered shared longevity mechanisms within and across species, including downregulated Igf1 and upregulated mitochondrial translation genes, and unique features, such as distinct regulation of the innate immune response and cellular respiration. Signatures of long-lived species were positively correlated with age-related changes and enriched for evolutionarily ancient essential genes, involved in proteolysis and PI3K-Akt signaling. Conversely, lifespan-extending interventions counteracted aging patterns and affected younger, mutable genes enriched for energy metabolism. The identified biomarkers revealed longevity interventions, including KU0063794, which extended mouse lifespan and healthspan. Overall, this study uncovers universal and distinct strategies of lifespan regulation within and across species and provides tools for discovering longevity interventions. Lifespan varies within and across species, but the general principles of its control remain unclear. Here, we conducted multi-tissue RNA-seq analyses across 41 mammalian species, identifying longevity signatures and examining their relationship with transcriptomic biomarkers of aging and established lifespan-extending interventions. An integrative analysis uncovered shared longevity mechanisms within and across species, including downregulated Igf1 and upregulated mitochondrial translation genes, and unique features, such as distinct regulation of the innate immune response and cellular respiration. Signatures of long-lived species were positively correlated with age-related changes and enriched for evolutionarily ancient essential genes, involved in proteolysis and PI3K-Akt signaling. Conversely, lifespan-extending interventions counteracted aging patterns and affected younger, mutable genes enriched for energy metabolism. The identified biomarkers revealed longevity interventions, including KU0063794, which extended mouse lifespan and healthspan. Overall, this study uncovers universal and distinct strategies of lifespan regulation within and across species and provides tools for discovering longevity interventions.
Citations by journals
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Nature
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Citations by publishers
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1
2
3
4
5
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5 publications, 20%
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Impact Journals
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Pleiades Publishing
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Tyshkovskiy A. et al. Distinct longevity mechanisms across and within species and their association with aging // Cell. 2023. Vol. 186. No. 13. p. 2929-2949.e20.
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Tyshkovskiy A., Ma S., Shindyapina A. V., Tikhonov S., Lee S., Bozaykut P., Castro J., Seluanov A., Schork N. J., Gorbunova V., Dmitriev S. E., G. F. Ulmishek, R. R. Charpentier, R. H., Gladyshev V. N. Distinct longevity mechanisms across and within species and their association with aging // Cell. 2023. Vol. 186. No. 13. p. 2929-2949.e20.
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TY - JOUR
DO - 10.1016/j.cell.2023.05.002
UR - https://doi.org/10.1016%2Fj.cell.2023.05.002
TI - Distinct longevity mechanisms across and within species and their association with aging
T2 - Cell
AU - Tyshkovskiy, Alexander
AU - Ma, Siming
AU - Shindyapina, Anastasia V.
AU - Tikhonov, Stanislav
AU - Lee, Sang-Goo
AU - Bozaykut, Perinur
AU - Castro, José
AU - Seluanov, Andrei
AU - Schork, Nicholas J.
AU - Gorbunova, Vera
AU - Dmitriev, Sergey E.
AU - G. F. Ulmishek, R. R. Charpentier,, Richard H.
AU - Gladyshev, Vadim N.
PY - 2023
DA - 2023/06/03 00:00:00
PB - Elsevier
SP - 2929-2949.e20
IS - 13
VL - 186
SN - 0092-8674
SN - 1097-4172
ER -
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@article{2023_Tyshkovskiy,
author = {Alexander Tyshkovskiy and Siming Ma and Anastasia V. Shindyapina and Stanislav Tikhonov and Sang-Goo Lee and Perinur Bozaykut and José Castro and Andrei Seluanov and Nicholas J. Schork and Vera Gorbunova and Sergey E. Dmitriev and Richard H. G. F. Ulmishek, R. R. Charpentier, and Vadim N. Gladyshev},
title = {Distinct longevity mechanisms across and within species and their association with aging},
journal = {Cell},
year = {2023},
volume = {186},
publisher = {Elsevier},
month = {jun},
url = {https://doi.org/10.1016%2Fj.cell.2023.05.002},
number = {13},
pages = {2929--2949.e20},
doi = {10.1016/j.cell.2023.05.002}
}
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Tyshkovskiy, Alexander, et al. “Distinct longevity mechanisms across and within species and their association with aging.” Cell, vol. 186, no. 13, Jun. 2023, pp. 2929-2949.e20. https://doi.org/10.1016%2Fj.cell.2023.05.002.
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