The Brain-body Energy Conservation Model of Aging

Overview

Journal Nat Aging

Specialty Geriatrics

Date 2024 Oct 8

PMID 39379694

Authors

Evan D Shaulson

Alan A Cohen

Martin Picard

Affiliations

Soon will be listed here.

Abstract

Aging involves seemingly paradoxical changes in energy metabolism. Molecular damage accumulation increases cellular energy expenditure, yet whole-body energy expenditure remains stable or decreases with age. We resolve this apparent contradiction by positioning the brain as the mediator and broker in the organismal energy economy. As somatic tissues accumulate damage over time, costly intracellular stress responses are activated, causing aging or senescent cells to secrete cytokines that convey increased cellular energy demand (hypermetabolism) to the brain. To conserve energy in the face of a shrinking energy budget, the brain deploys energy conservation responses, which suppress low-priority processes, producing fatigue, physical inactivity, blunted sensory capacities, immune alterations and endocrine 'deficits'. We term this cascade the brain-body energy conservation (BEC) model of aging. The BEC outlines (1) the energetic cost of cellular aging, (2) how brain perception of senescence-associated hypermetabolism may drive the phenotypic manifestations of aging and (3) energetic principles underlying the modifiability of aging trajectories by stressors and geroscience interventions.

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References

McEwen B . Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007; 87(3):873-904. DOI: 10.1152/physrev.00041.2006. View

Doyle J, Csete M . Architecture, constraints, and behavior. Proc Natl Acad Sci U S A. 2011; 108 Suppl 3:15624-30. PMC: 3176601. DOI: 10.1073/pnas.1103557108. View

Finkel T . The metabolic regulation of aging. Nat Med. 2015; 21(12):1416-23. DOI: 10.1038/nm.3998. View

Gonzalez A, Hall M, Lin S, Grahame Hardie D . AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control. Cell Metab. 2020; 31(3):472-492. DOI: 10.1016/j.cmet.2020.01.015. View

Huynh M, Kinyua A, Yang D, Kim K . Hypothalamic AMPK as a Regulator of Energy Homeostasis. Neural Plast. 2016; 2016:2754078. PMC: 4980534. DOI: 10.1155/2016/2754078. View

Pontzer H, McGrosky A . Balancing growth, reproduction, maintenance, and activity in evolved energy economies. Curr Biol. 2022; 32(12):R709-R719. DOI: 10.1016/j.cub.2022.05.018. View

Lopez-Otin C, Galluzzi L, Freije J, Madeo F, Kroemer G . Metabolic Control of Longevity. Cell. 2016; 166(4):802-821. DOI: 10.1016/j.cell.2016.07.031. View

Moqri M, Herzog C, Poganik J, Justice J, Belsky D, Higgins-Chen A . Biomarkers of aging for the identification and evaluation of longevity interventions. Cell. 2023; 186(18):3758-3775. PMC: 11088934. DOI: 10.1016/j.cell.2023.08.003. View

Kaeberlein M, Rabinovitch P, Martin G . Healthy aging: The ultimate preventative medicine. Science. 2016; 350(6265):1191-3. PMC: 4793924. DOI: 10.1126/science.aad3267. View

10.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . Hallmarks of aging: An expanding universe. Cell. 2023; 186(2):243-278. DOI: 10.1016/j.cell.2022.11.001. View

11.

Wiley C, Campisi J . The metabolic roots of senescence: mechanisms and opportunities for intervention. Nat Metab. 2021; 3(10):1290-1301. PMC: 8889622. DOI: 10.1038/s42255-021-00483-8. View

12.

Jang J, Blum A, Liu J, Finkel T . The role of mitochondria in aging. J Clin Invest. 2018; 128(9):3662-3670. PMC: 6118639. DOI: 10.1172/JCI120842. View

13.

Moldakozhayev A, Gladyshev V . Metabolism, homeostasis, and aging. Trends Endocrinol Metab. 2023; 34(3):158-169. PMC: 11096277. DOI: 10.1016/j.tem.2023.01.003. View

14.

Bobba-Alves N, Juster R, Picard M . The energetic cost of allostasis and allostatic load. Psychoneuroendocrinology. 2022; 146:105951. PMC: 10082134. DOI: 10.1016/j.psyneuen.2022.105951. View

15.

Nelson P, Masel J . Intercellular competition and the inevitability of multicellular aging. Proc Natl Acad Sci U S A. 2017; 114(49):12982-12987. PMC: 5724245. DOI: 10.1073/pnas.1618854114. View

16.

Levin M . Bioelectric signaling: Reprogrammable circuits underlying embryogenesis, regeneration, and cancer. Cell. 2021; 184(8):1971-1989. DOI: 10.1016/j.cell.2021.02.034. View

17.

Picard M, Shirihai O . Mitochondrial signal transduction. Cell Metab. 2022; 34(11):1620-1653. PMC: 9692202. DOI: 10.1016/j.cmet.2022.10.008. View

18.

Miller H, Dean E, Pletcher S, Leiser S . Cell non-autonomous regulation of health and longevity. Elife. 2020; 9. PMC: 7728442. DOI: 10.7554/eLife.62659. View

19.

Fried L, Cohen A, Xue Q, Walston J, Bandeen-Roche K, Varadhan R . The physical frailty syndrome as a transition from homeostatic symphony to cacophony. Nat Aging. 2021; 1(1):36-46. PMC: 8409463. DOI: 10.1038/s43587-020-00017-z. View

20.

Cohen A, Ferrucci L, Fulop T, Gravel D, Hao N, Kriete A . A complex systems approach to aging biology. Nat Aging. 2023; 2(7):580-591. DOI: 10.1038/s43587-022-00252-6. View