Biological age is increased by stress and restored upon recovery

Jesse R Poganik; Bohan Zhang; Gurpreet S Baht; Alexander Tyshkovskiy; Amy Deik; Csaba Kerepesi; Sun Hee Yim; Ake T Lu; Amin Haghani; Tong Gong; Anna M Hedman; Ellika Andolf; Göran Pershagen; Catarina Almqvist; Clary B Clish; Steve Horvath; James P White; Vadim N Gladyshev

doi:10.1016/j.cmet.2023.03.015

Biological age is increased by stress and restored upon recovery

Cell Metab. 2023 May 2;35(5):807-820.e5. doi: 10.1016/j.cmet.2023.03.015. Epub 2023 Apr 21.

Authors

Jesse R Poganik¹, Bohan Zhang¹, Gurpreet S Baht², Alexander Tyshkovskiy¹, Amy Deik³, Csaba Kerepesi⁴, Sun Hee Yim¹, Ake T Lu⁵, Amin Haghani⁵, Tong Gong⁶, Anna M Hedman⁶, Ellika Andolf⁷, Göran Pershagen⁸, Catarina Almqvist⁹, Clary B Clish³, Steve Horvath¹⁰, James P White¹¹, Vadim N Gladyshev¹²

Affiliations

¹ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
² Department of Orthopaedic Surgery, Duke University, Durham, NC 27701, USA; Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA.
³ Broad Institute of MIT and Harvard, Cambridge, MA 01241, USA.
⁴ Institute for Computer Science and Control (SZTAKI), Eötvös Loránd Research Network, Budapest, 1111, Hungary.
⁵ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Altos Labs, San Diego, CA, USA.
⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷ Department of Clinical Sciences, Division of Obstetrics and Gynaecology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
⁸ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden.
⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
¹⁰ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Altos Labs, San Diego, CA, USA; Department of Biostatistics, School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹¹ Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27701, USA. Electronic address: [email protected].
¹² Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 01241, USA. Electronic address: [email protected].

Abstract

Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report that biological age is fluid and exhibits rapid changes in both directions. At epigenetic, transcriptomic, and metabolomic levels, we find that the biological age of young mice is increased by heterochronic parabiosis and restored following surgical detachment. We also identify transient changes in biological age during major surgery, pregnancy, and severe COVID-19 in humans and/or mice. Together, these data show that biological age undergoes a rapid increase in response to diverse forms of stress, which is reversed following recovery from stress. Our study uncovers a new layer of aging dynamics that should be considered in future studies. The elevation of biological age by stress may be a quantifiable and actionable target for future interventions.

Keywords: aging; biological age; dynamics; epigenetic aging clocks; recovery; stress.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aging / physiology
Animals
COVID-19*
Humans
Mice
Parabiosis

Abstract

Publication types

MeSH terms

Grants and funding