Weiss, E. P. et al. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. Am. J. Clin. Nutr. 84, 1033–1042 (2006).
Fontana, L. et al. Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized, controlled trial. Am. J. Physiol.-Endocrinol. Metab. 293, E197–E202 (2007).
Racette, S. B. et al. One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. J. Gerontol. Seri. A: Biol. Sci. Med. Sci. 61, 943–950 (2006).
Hofer, T. et al. Long-term effects of caloric restriction or exercise on DNA and RNA oxidation levels in white blood cells and urine in humans. Rejuvenation Res. 11, 793–799 (2008).
Fontana, L., Klein, S. & Holloszy, J. O. Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production. Age 32, 97–108 (2010).
Riordan, M. M. et al. The effects of caloric restriction- and exercise-induced weight loss on left ventricular diastolic function. Am. J. Physiol. Heart Circ. Physiol. 294, H1174–H1182 (2008).
Matthews, C. E. et al. Amount and intensity of leisure-time physical activity and lower cancer risk. J. Clin. Oncol. 38, 686–697 (2020).
Moore, S. C. et al. Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA Int. Med. 176, 816–825 (2016).
Giovannucci, E. et al. Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann. Int. Med. 122, 327–334 (1995).
Meyerhardt, J. A. et al. Physical activity and survival after colorectal cancer diagnosis. J. Clin. Oncol. 24, 3527–3534 (2006).
Zhong, S. et al. Association between physical activity and mortality in breast cancer: a meta-analysis of cohort studies. Eur. J. Epidemiol. 29, 391–404 (2014).
McTiernan, A. Mechanisms linking physical activity with cancer. Nat. Rev. Cancer 8, 205–211 (2008).
Borghesan, M., Hoogaars, W. M. H., Varela-Eirin, M., Talma, N. & Demaria, M. A senescence-centric view of aging: implications for longevity and disease. Trends Cell Biol. 30, 777–791 (2020).
Sharpless, N. E. & Sherr, C. J. Forging a signature of in vivo senescence. Nat. Rev. Cancer 15, 397–408 (2015).
Kuilman, T., Michaloglou, C., Mooi, W. J. & Peeper, D. S. The essence of senescence. Genes Dev. 24, 2463–2479 (2010).
Hernandez-Segura, A. et al. Unmasking transcriptional heterogeneity in senescent cells. Curr. Biol. 27, 2652–2660. e2654 (2017).
Casella, G. et al. Transcriptome signature of cellular senescence. Nucleic Acids Res. 47, 7294–7305 (2019).
van Deursen, J. M. The role of senescent cells in ageing. Nature 509, 439–446 (2014).
Demaria, M. et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31, 722–733 (2014).
Baker, D. J. et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530, 184–189 (2016).
Burd, C. E. et al. Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model. Cell 152, 340–351 (2013).
Yamakoshi, K. et al. Real-time in vivo imaging of p16Ink4a reveals cross talk with p53. J. Cell Biol. 186, 393–407 (2009).
Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018).
Fontana, L. et al. The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon. Aging Cell 17, e12746 (2018).
Green, C. L., Lamming, D. W. & Fontana, L. Molecular mechanisms of dietary restriction promoting health and longevity. Nat. Rev. Mol. Cell Biol. 23, 56–73 (2022).
Nehme, J. et al. High dietary protein and fat contents exacerbate hepatic senescence and SASP in mice. FEBS J. https://doi.org/10.1111/febs.16292 (2021).
Englund, D. A. et al. Exercise reduces circulating biomarkers of cellular senescence in humans. Aging Cell 20, e13415 (2021).
Justice, J. N. et al. Cellular senescence biomarker p16INK4a+ cell burden in thigh adipose is associated with poor physical function in older women. J. Gerontol. A Biol. Sci. Med. Sci. 73, 939–945 (2018).
Chen, X. K. et al. Is exercise a senolytic medicine? A systematic review. Aging Cell 20, e13294 (2021).
Manninen, V. et al. Joint effects of serum triglyceride and ldl cholesterol and Hdl cholesterol concentrations on coronary heart-disease risk in the helsinki heart-study – implications for treatment. Circulation 85, 37–45 (1992).
McLaughlin, T. et al. Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann. Int. Med. 139, 802–809 (2003).
Bayerdorffer, E. et al. Decreased high-density-lipoprotein cholesterol and increased low-density cholesterol levels in patients with colorectal adenomas. Ann. Int. Med. 118, 481–487 (1993).
Cespedes Feliciano, E. M. et al. Metabolic dysfunction, obesity, and survival among patients with early-stage colorectal cancer. J. Clin. Oncol. 34, 3664 (2016).
Kammire, M. S. et al. Does walking during chemotherapy impact p16(INK4a) levels in women with early breast cancer. J. Clin. Lab. Anal. 36, e24753 (2022).
Lavin, K. M. et al. Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation in women. J. Appl. Physiol. (1985) 129, 1493–1504 (2020).
Nilsson, M. I. et al. Lifelong aerobic exercise protects against inflammaging and cancer. PLoS ONE 14, e0210863 (2019).
Kohrt, W. M. et al. Effects of gender, age, and fitness level on response of VO2max to training in 60–71 yr olds. J. Appl. Physiol. (1985) 71, 2004–2011 (1991).
