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Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity
Open accessAbstract
Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio‐economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been ‘compression of morbidity’ and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, ‘geroscience’, is focused on healthspan extension. Superimposed on this background are new attitudes and demand for ‘optimal longevity’ – living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first‐line function‐preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel ‘nutraceutical’ compounds, serving as potential complementary approaches. Future research efforts should focus on defining the temporal patterns of functional declines with ageing, identifying the underlying mechanisms and modulatory factors involved, and establishing the most effective lifestyle practices and pharmacological options for maintaining function. Continuing development of effective behavioural approaches for enhancing adherence to healthy ageing practices in diverse populations, and ongoing analysis of the socio‐economic costs and benefits of healthspan extension will be important supporting goals. To meet the demands created by rapid population ageing, a new emphasis in physiological geroscience is needed, which will require the collaborative, interdisciplinary efforts of investigators working throughout the translational research continuum from basic science to public health.
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Cites
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
Jemal, A., Siegel, R., Xu, J., & Ward, E. (2010) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20073 · Cited by 12,596
Gait speed and survival in older adults.
Studenski, S. (2011) · JAMA · doi:10.1001/jama.2010.1923 · Cited by 4,558 · cited 1×
“…example, in late-middle-aged/older adults, cardiorespiratory fitness (aerobic exercise capacity) (Lee et al. 2011; Vigen et al. 2012), gait speed (Studenski et al. 2011), grip strength (Rantanen et al. 2012) and integrative neuromuscular tasks, such as the ability to sit and rise from…”
BackgroundBlessed, G., Tomlinson, B. E., & Roth, M. (1968) · British Journal of Psychiatry · doi:10.1192/bjp.114.512.797 · Cited by 4,117
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
Aging, natural death, and the compression of morbidity
Fries, J. F. (1980) · New England Journal of Medicine · doi:10.1056/nejm198007173030304 · Cited by 3,356
Heidenreich, P. A., Trogdon, J. G., Khavjou, O. A., Butler, J., Dracup, K., Ezekowitz, M. D., Finkelstein, E. A., Hong, Y., Johnston, S. C., Khera, A., et al. (2011) · Circulation · doi:10.1161/cir.0b013e31820a55f5 · Cited by 3,208
Geroscience: Linking Aging to Chronic Disease
Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.039 · Cited by 2,764
Lakatta, E. G., & Levy, D. (2003) · Circulation · doi:10.1161/01.cir.0000048892.83521.58 · Cited by 2,244
Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107
Cited by
Making sense of the ageing methylome
Seale, K., Horvath, S., Teschendorff, A., Eynon, N., & Voisin, S. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00477-6 · Cited by 274
Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement
Tenchov, R., Sasso, J. M., Wang, X., & Zhou, Q. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00531 · Cited by 276
Physical activity, aging, and physiological function
Harridge, S. D. R., & Lazarus, N. R. (2017) · Physiology · doi:10.1152/physiol.00029.2016 · Cited by 214
Sánchez-Sánchez, J. L., Lu, W.-H., Gallardo-Gómez, D., del Pozo Cruz, B., de Souto Barreto, P., Lucia, A., & Valenzuela, P. L. (2024) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(24)00092-8 · Cited by 180
Justice, J. N., Gregory, H., Tchkonia, T., LeBrasseur, N. K., Kirkland, J. L., Kritchevsky, S. B., & Nicklas, B. J. (2018) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glx134 · Cited by 129
Self-citationDeclining performance of master athletes: silhouettes of the trajectory of healthy human ageing?
Lazarus, N. R., & Harridge, S. D. R. (2017) · The Journal of Physiology · doi:10.1113/jp272443 · Cited by 116
Muscle morphology and performance in master athletes: A systematic review and meta-analyses
Mckendry, J., Breen, L., Shad, B. J., & Greig, C. A. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.04.007 · Cited by 111
Sánchez-Sánchez, J. L., de Souto Barreto, P., Antón-Rodrigo, I., Ramón-Espinoza, F., Marín-Epelde, I., Sánchez-Latorre, M., Moral-Cuesta, D., & Casas-Herrero, Á. (2022) · Age and Ageing · doi:10.1093/ageing/afac303 · Cited by 106
Justice, J., Miller, J. D., Newman, J. C., Hashmi, S. K., Halter, J., Austad, S. N., Barzilai, N., & Kirkland, J. L. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glw126 · Cited by 96
Self-citationNutrition and longevity—From mechanisms to uncertainties
Ekmekcioglu, C. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2019.1676698 · Cited by 87
Nutrition and other lifestyle influences on arterial aging
LaRocca, T. J., Martens, C. R., & Seals, D. R. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.002 · Cited by 83
Self-citationExercise-Induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension
Musci, R., Hamilton, K., & Linden, M. (2019) · Sports · doi:10.3390/sports7070170 · Cited by 73
Nitric oxide, aging and aerobic exercise: Sedentary individuals to Master's athletes
Shannon, O. M., Clifford, T., Seals, D. R., Craighead, D. H., & Rossman, M. J. (2022) · Nitric Oxide · doi:10.1016/j.niox.2022.06.002 · Cited by 51
Self-citationBallak, D. B., Brunt, V. E., Sapinsley, Z. J., Ziemba, B. P., Richey, J. J., Zigler, M. C., Johnson, L. C., Gioscia‐Ryan, R. A., Culp‐Hill, R., Eisenmesser, E. Z., et al. (2020) · Aging Cell · doi:10.1111/acel.13074 · Cited by 44
Self-citationRebsamen, S., Knols, R. H., Pfister, P. B., & de Bruin, E. D. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01019 · Cited by 39
Reprogramming: Emerging Strategies to Rejuvenate Aging Cells and Tissues
Alle, Q., Le Borgne, E., Milhavet, O., & Lemaitre, J.-M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22083990 · Cited by 35
Exercise prevents impaired autophagy and proteostasis in a model of neurogenic myopathy
Campos, J. C., Baehr, L. M., Gomes, K. M. S., Bechara, L. R. G., Voltarelli, V. A., Bozi, L. H. M., Ribeiro, M. A. C., Ferreira, N. D., Moreira, J. B. N., Brum, P. C., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-30365-1 · Cited by 32
Carter, S. J., Gruber, A. H., Raglin, J. S., Baranauskas, M. N., & Coggan, A. R. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.109732 · Cited by 21
Compression of morbidity by interventions that steepen the survival curve
Yang, Y., Mayo, A., Levy, T., Raz, N., Shenhar, B., Jarosz, D. F., & Alon, U. (2025) · Nature Communications · doi:10.1038/s41467-025-57807-5 · Cited by 18
Yu, K., Vyavahare, S., Alhamad, D., Bensreti, H., Ruan, L., Tuladhar, A., Dai, C., Shaver, J. C., Tripathi, A., Ding, K., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.192047 · Cited by 12
β 2 ‐adrenoceptor activation improves skeletal muscle autophagy in neurogenic myopathy
Campos, J. C., Baehr, L. M., Ferreira, N. D., Bozi, L. H. M., Andres, A. M., Ribeiro, M. A. C., Gottlieb, R. A., Bodine, S. C., & Ferreira, J. C. B. (2020) · The FASEB Journal · doi:10.1096/fj.201902305r · Cited by 10
The New Frontier of Ageing: Innovations and Insights in Gerontology
Tohit, N. F. M., & Haque, M. (2024) · Advances in Human Biology · doi:10.4103/aihb.aihb_110_24 · Cited by 8
Metadata
- Authors
- Seals, D. R., Justice, J. N., & LaRocca, T. J.
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2015-03-11
- Volume
- 594
- Issue
- 8
- Pages
- 2001-2024
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- OpenAlex
- W1583921993
- Cited by
- 312
- References
- 50
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Open access
- green
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