The exposome of healthy and accelerated aging across 40 countries

Hernan Hernandez^#¹, Hernando Santamaria-Garcia^#^{2

3}, Sebastian Moguilner^{1

4

5}, Francesca R Farina^{6

7}, Agustina Legaz^{1

4}, Pavel Prado⁸, Jhosmary Cuadros^{1

9

10}, Liset Gonzalez¹¹, Raul Gonzalez-Gomez¹, Joaquín Migeot^{1

6}, Carlos Coronel-Oliveros^{1

6

12}, Enzo Tagliazucchi^{1

13}, Marcelo Adrián Maito^{1

4}, María E Godoy^{1

4}, Josephine Cruzat¹, Ahmed Shaheen¹⁴, Temitope Farombi¹⁵, Daniel Salazar¹⁶, Lucas Uglione Da Ros¹⁷, Wyllians V Borelli^{17

18

19}, Eduardo R Zimmer^{19

20}, Alfred K Njamnshi^{21

22

23}, Swati Bajpai^{6

24}, A B Dey²⁴, Cyprian Mostert^{25

26}, Zul Merali^{25

27

28}, Mohamed Salama^{6

29

30}, Sara A Moustafa^{6

29

30}, Sol Fittipaldi^{1

6

31}, Florencia Altschuler⁴, Vicente Medel¹, David Huepe³², Kristine Yaffe^{33

34

35}, Chinedu Momoh²⁵, Harris A Eyre^{36

37

38}, Pawel Swieboda^{39

40}, Brian Lawlor^{6

31}, J Jaime Miranda^{41

42}, Claudia Duran-Aniotz¹, Sandra Baez^{43

44}, Agustin Ibanez^{45

46

47

48}

Affiliations

¹ Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Santiago de Chile, Chile.
² PhD Program in Neuroscience, Pontificia Universidad Javeriana, Bogotá, Colombia.
³ Center of Memory and Cognition Intellectus, Hospital Universitario San Ignacio, Bogotá, Colombia.
⁴ Cognitive Neuroscience Center, Universidad de San Andrés, Buenos Aires, Argentina.
⁵ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland.
⁷ Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
⁸ Escuela de Fonoaudiología, Facultad de Odontología y Ciencias de la Rehabilitación, Universidad San Sebastián, Santiago de Chile, Chile.
⁹ Grupo de Bioingeniería, Decanato de Investigación, Universidad Nacional Experimental del Táchira, San Cristóbal, Venezuela.
¹⁰ Advanced Center for Electrical and Electronic Engineering, Universidad Técnica Federico Santa María, Valparaíso, Chile.
¹¹ Facultad de Ingeniería, Universidad de Concepción, Concepción, Chile.
¹² Trinity College Dublin, The University of Dublin, Dublin, Ireland.
¹³ University of Buenos Aires, Buenos Aires, Argentina.
¹⁴ Alexandria Faculty of Medicine, Alexandria, Egypt.
¹⁵ Department of Medicine, University College Hospital, Ibadan, Nigeria.
¹⁶ London School of Economics and Political Science, London, UK.
¹⁷ Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
¹⁸ Department of Morphological Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
¹⁹ Graduate Program in Biological Sciences: Biochemistry (PPGBioq), UFRGS, Porto Alegre, Brazil.
²⁰ Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
²¹ Brain Research Africa Initiative (BRAIN), Yaounde, Cameroon.
²² Neuroscience Lab, Faculty of Medicine and Biomedical Sciences, The University of Yaounde I, Yoaunde, Cameroon.
²³ Neurology Department, Central Hospital Yaounde, Yaounde, Cameroon.
²⁴ All India Institute of Medical Sciences, New Delhi, India.
²⁵ Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
²⁶ Department of Population Health, Aga Khan University, Nairobi, Kenya.
²⁷ University of Ottawa, Ottawa, Ontario, Canada.
²⁸ Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
²⁹ Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt.
³⁰ Faculty of Medicine, Mansoura University, Mansoura, Egypt.
³¹ School of Psychology, Trinity College Dublin, Dublin, Ireland.
³² Center for Social and Cognitive Neuroscience, School of Psychology, Universidad Adolfo Ibáñez, Santiago, Chile.
³³ Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
³⁴ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
³⁵ Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
³⁶ Neuro-Policy Program, Center for Health and Biosciences, Baker Institute for Public Policy, Rice University, Houston, TX, USA.
³⁷ Euro-Mediterranean Economists Association, Barcelona, Spain.
³⁸ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA.
³⁹ International Center for Future Generations (ICFG), Brussels, Belgium.
⁴⁰ Brain Capital Alliance, San Francisco, CA, USA.
⁴¹ Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁴² CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.
⁴³ Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland. sandra.baez@gbhi.org.
⁴⁴ Universidad de los Andes, Bogota, Colombia. sandra.baez@gbhi.org.
⁴⁵ Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Santiago de Chile, Chile. agustin.ibanez@gbhi.org.
⁴⁶ Cognitive Neuroscience Center, Universidad de San Andrés, Buenos Aires, Argentina. agustin.ibanez@gbhi.org.
⁴⁷ Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland. agustin.ibanez@gbhi.org.
⁴⁸ Trinity College Dublin, The University of Dublin, Dublin, Ireland. agustin.ibanez@gbhi.org.

^# Contributed equally.

PMID: 40659767
DOI: 10.1038/s41591-025-03808-2

The exposome of healthy and accelerated aging across 40 countries

Hernan Hernandez et al. Nat Med. 2025 Sep.

. 2025 Sep;31(9):3089-3100.

doi: 10.1038/s41591-025-03808-2. Epub 2025 Jul 14.

Authors

Affiliations

¹ Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Santiago de Chile, Chile.
² PhD Program in Neuroscience, Pontificia Universidad Javeriana, Bogotá, Colombia.
³ Center of Memory and Cognition Intellectus, Hospital Universitario San Ignacio, Bogotá, Colombia.
⁴ Cognitive Neuroscience Center, Universidad de San Andrés, Buenos Aires, Argentina.
⁵ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland.
⁷ Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
⁸ Escuela de Fonoaudiología, Facultad de Odontología y Ciencias de la Rehabilitación, Universidad San Sebastián, Santiago de Chile, Chile.
⁹ Grupo de Bioingeniería, Decanato de Investigación, Universidad Nacional Experimental del Táchira, San Cristóbal, Venezuela.
¹⁰ Advanced Center for Electrical and Electronic Engineering, Universidad Técnica Federico Santa María, Valparaíso, Chile.
¹¹ Facultad de Ingeniería, Universidad de Concepción, Concepción, Chile.
¹² Trinity College Dublin, The University of Dublin, Dublin, Ireland.
¹³ University of Buenos Aires, Buenos Aires, Argentina.
¹⁴ Alexandria Faculty of Medicine, Alexandria, Egypt.
¹⁵ Department of Medicine, University College Hospital, Ibadan, Nigeria.
¹⁶ London School of Economics and Political Science, London, UK.
¹⁷ Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
¹⁸ Department of Morphological Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
¹⁹ Graduate Program in Biological Sciences: Biochemistry (PPGBioq), UFRGS, Porto Alegre, Brazil.
²⁰ Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
²¹ Brain Research Africa Initiative (BRAIN), Yaounde, Cameroon.
²² Neuroscience Lab, Faculty of Medicine and Biomedical Sciences, The University of Yaounde I, Yoaunde, Cameroon.
²³ Neurology Department, Central Hospital Yaounde, Yaounde, Cameroon.
²⁴ All India Institute of Medical Sciences, New Delhi, India.
²⁵ Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
²⁶ Department of Population Health, Aga Khan University, Nairobi, Kenya.
²⁷ University of Ottawa, Ottawa, Ontario, Canada.
²⁸ Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
²⁹ Institute of Global Health and Human Ecology, The American University in Cairo, New Cairo, Egypt.
³⁰ Faculty of Medicine, Mansoura University, Mansoura, Egypt.
³¹ School of Psychology, Trinity College Dublin, Dublin, Ireland.
³² Center for Social and Cognitive Neuroscience, School of Psychology, Universidad Adolfo Ibáñez, Santiago, Chile.
³³ Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
³⁴ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
³⁵ Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
³⁶ Neuro-Policy Program, Center for Health and Biosciences, Baker Institute for Public Policy, Rice University, Houston, TX, USA.
³⁷ Euro-Mediterranean Economists Association, Barcelona, Spain.
³⁸ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA.
³⁹ International Center for Future Generations (ICFG), Brussels, Belgium.
⁴⁰ Brain Capital Alliance, San Francisco, CA, USA.
⁴¹ Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁴² CRONICAS Center of Excellence in Chronic Diseases, Universidad Peruana Cayetano Heredia, Lima, Peru.
⁴³ Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland. sandra.baez@gbhi.org.
⁴⁴ Universidad de los Andes, Bogota, Colombia. sandra.baez@gbhi.org.
⁴⁵ Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Santiago de Chile, Chile. agustin.ibanez@gbhi.org.
⁴⁶ Cognitive Neuroscience Center, Universidad de San Andrés, Buenos Aires, Argentina. agustin.ibanez@gbhi.org.
⁴⁷ Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland. agustin.ibanez@gbhi.org.
⁴⁸ Trinity College Dublin, The University of Dublin, Dublin, Ireland. agustin.ibanez@gbhi.org.

^# Contributed equally.

PMID: 40659767
DOI: 10.1038/s41591-025-03808-2

Abstract

Protective and risk factors can drive healthy or accelerated aging, with distinct environments modulating their effects. The impact of the exposome-the combined physical and social exposures experienced throughout life-on accelerated aging remains unknown. We assessed delayed and accelerated aging in 161,981 participants from 40 countries (45.09% female; mean age, 67.06; s.d., 9.85) by measuring biobehavioral age gaps (BBAGs), defined as the difference between estimated age from protective and risk factors and chronological age, in cross-sectional and longitudinal designs. BBAGs predicted chronological age, followed by regional and exposomal factor analyses, linked to accelerated aging. Europe led in healthy aging, while Egypt and South Africa showed the greatest acceleration; Asia and Latin America fell in between (Cliff's delta (δd) = 0.15-0.52; all P < 0.0001). Accelerated aging was more evident in eastern and southern Europe; globally, it was also associated with lower income (δd = 0.48-0.56, P < 1 × 10^-15). Exposomal factors of accelerated aging include physical (air quality), social (socioeconomic and gender inequality, migration) and sociopolitical (representation, party freedom, suffrage, elections and democracy) determinants (all Cohen's d (d) > 0.37, P < 0.0001). BBAGs predicted future functional (r (Pearson correlation) = -0.33, P < 1 × 10^-15, d = 0.70) and cognitive declines (r = -0.22, P < 1 × 10^-15, d = 0.44), and larger BBAGs (P < 0.0001, d = 1.55). Healthy and accelerated aging are influenced by physical, social and sociopolitical exposomes, with considerable disparities across nations.

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Conflict of interest statement

Competing interests: E.R.Z. has served on scientific advisory boards for Nintx, Novo Nordisk and Masima. He is also a cofounder and a minority shareholder at Masima. The other authors declare no competing interests.

References

1. Fried, L. P. & Rowe, J. W. Health in aging—past, present, and future. N. Engl. J. Med. 383, 1293–1296 (2020). - PubMed
1. Moguilner, S. et al. Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations. Nat. Med. 30, 3646–3657 (2024). - PubMed - PMC
1. Tian, Y. E. et al. Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality. Nat. Med. 29, 1221–1231 (2023). - PubMed
1. Nowogrodzki, J. What accelerates brain ageing? This AI ‘brain clock’ points to answers. Nature 633, 20 (2024). - PubMed
1. Allada, R. & Bass, J. Circadian mechanisms in medicine. N. Engl. J. Med. 384, 550–561 (2021). - PubMed - PMC

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The exposome of healthy and accelerated aging across 40 countries

Affiliations

The exposome of healthy and accelerated aging across 40 countries

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

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