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Unlock the Science of Longevity

Understanding Cellular Age Reversal

Understanding the science behind fat loss is pivotal for more than just weight management; it profoundly influences the aging process. This exploration reveals how obesity accelerates aging through detrimental effects on critical biological mechanisms, and how fat loss can counteract these effects, promoting longevity and overall health. The following sections will delve into these impacts, showcasing the significant relationship between body weight and the aging process in a concise and insightful manner.

The Science of Aging and Fat Loss

Understanding the 12 Hallmarks of Aging

Sources

GENOMIC INSTABILITY

(1) Jovanović M, Kovačević S, Brkljačić J, Djordjevic A. Oxidative Stress Linking Obesity and Cancer: Is Obesity a ‘Radical Trigger’ to Cancer? Int J Mol Sci. 2023 May 8;24(9):8452. doi: 10.3390/ijms24098452. PMID: 37176160; PMCID: PMC10179114.

(2) Usman M, Woloshynowych M, Britto JC, Bilkevic I, Glassar B, Chapman S, Ford-Adams ME, Desai A, Bain M, Tewfik I, Volpi EV. Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents. Int J Obes (Lond). 2021 Sep;45(9):2095-2107. doi: 10.1038/s41366-021-00879-2. Epub 2021 Jun 22. PMID: 34158611; PMCID: PMC8380542.

(3) Włodarczyk M, Nowicka G. Obesity, DNA Damage, and Development of Obesity-Related Diseases. Int J Mol Sci. 2019 Mar 6;20(5):1146. doi: 10.3390/ijms20051146. PMID: 30845725; PMCID: PMC6429223

(4) Smith ENL, Chandanathil M, Millis RM. Epigenetic Mechanisms in Obesity: Broadening Our Understanding of the Disease. Cureus. 2023 Oct 28;15(10):e47875. doi: 10.7759/cureus.47875. PMID: 37899888; PMCID: PMC10612994.

TELEMER ATTRITION

(5) Khosravaniardakani S, Bokov DO, Mahmudiono T, Hashemi SS, Nikrad N, Rabieemotmaen S, Abbasalizad-Farhangi M. Obesity Accelerates Leukocyte Telomere Length Shortening in Apparently Healthy Adults: A Meta-Analysis. Front Nutr. 2022 May 26;9:812846. doi: 10.3389/fnut.2022.812846. PMID: 35719148; PMCID: PMC9199514.

(6) Shin YA. How Does Obesity and Physical Activity Affect Aging?: Focused on Telomere as a Biomarker of Aging. J Obes Metab Syndr. 2019 Jun;28(2):92-104. doi: 10.7570/jomes.2019.28.2.92. Epub 2019 Jun 30. PMID: 31294341; PMCID: PMC6604845.

(7) Salvestrini Valentina, Sell Christian, Lorenzini Antonello, Obesity May Accelerate the Aging Process. Frontiers in Endocrinology. VOL10, 2019. https://www.frontiersin.org/articles/10.3389/fendo.2019.00266. DOI=10.3389/fendo.2019.00266. ISSN 1664-2392.

(8) D’Angelo S. Diet and Aging: The Role of Polyphenol-Rich Diets in Slow Down the Shortening of Telomeres: A Review. Antioxidants (Basel). 2023 Dec 7;12(12):2086. doi: 10.3390/antiox12122086. PMID: 38136206; PMCID: PMC10740764.

EPIGENETIC ALTERATIONS

(1) Smith ENL, Chandanathil M, Millis RM. Epigenetic Mechanisms in Obesity: Broadening Our Understanding of the Disease. Cureus. 2023 Oct 28;15(10):e47875. doi: 10.7759/cureus.47875. PMID: 37899888; PMCID: PMC10612994.

(2) Mahmoud AM. An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions. Int J Mol Sci. 2022 Jan 25;23(3):1341. doi: 10.3390/ijms23031341. PMID: 35163268; PMCID: PMC8836029.

(3) Contreras Raian E., Schriever Sonja C., Pfluger Paul T. Physiological and Epigenetic Features of Yoyo Dieting and Weight Control. Frontiers in Genetics. VOL10. 2019. https://www.frontiersin.org/articles/10.3389/fgene.2019.01015. DOI=10.3389/fgene.2019.01015. ISSN 1664-8021

(4) Wu, FY., Yin, RX. Recent progress in epigenetics of obesity. Diabetol Metab Syndr 14, 171 (2022). https://doi.org/10.1186/s13098-022-00947-1

LOSS OF PROTEOSTASIS

(5) Anderson SR, Gilge DA, Steiber AL, Previs SF. Diet-induced obesity alters protein synthesis: tissue-specific effects in fasted versus fed mice. Metabolism. 2008 Mar;57(3):347-54. doi: 10.1016/j.metabol.2007.10.009. PMID: 18249206; PMCID: PMC2323208.

(6) Beals Joseph W., Burd Nicholas A., Moore Daniel R., van Vliet Stephan. Obesity Alters the Muscle Protein Synthetic Response to Nutrition and Exercise. Frontiers in Nutrition. VOL 6. 2019. URL=https://www.frontiersin.org/articles/10.3389/fnut.2019.00087. DOI 10.3389/fnut.2019.00087. ISSN 2296-861X

(7) Villareal DT, Smith GI, Shah K, Mittendorfer B. Effect of weight loss on the rate of muscle protein synthesis during fasted and fed conditions in obese older adults. Obesity (Silver Spring). 2012 Sep;20(9):1780-6. doi: 10.1038/oby.2011.280. Epub 2011 Sep 22. PMID: 21938075; PMCID: PMC3291735.

(8) Włodarczyk M, Nowicka G. Obesity, DNA Damage, and Development of Obesity-Related Diseases. Int J Mol Sci. 2019 Mar 6;20(5):1146. doi: 10.3390/ijms20051146. PMID: 30845725; PMCID: PMC6429223.

DEREGULATED NUTRIENT SENSING

(1) Duca, F.A., Waise, T.M.Z., Peppler, W.T. et al. The metabolic impact of small intestinal nutrient sensing. Nat Commun 12, 903 (2021). https://doi.org/10.1038/s41467-021-21235-y

(2) Silvana Obici, Luciano Rossetti, Minireview: Nutrient Sensing and the Regulation of Insulin Action and Energy Balance, Endocrinology, Volume 144, Issue 12, 1 December 2003, Pages 5172–5178, https://doi.org/10.1210/en.2003-0999

(3) Ryan DH, Yockey SR. Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over. Curr Obes Rep. 2017 Jun;6(2):187-194. doi: 10.1007/s13679-017-0262-y. PMID: 28455679; PMCID: PMC5497590.

(4) Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/

MITOCHONDRIAL DYSFUNCTION

(5) Lee JH, Park A, Oh KJ, Lee SC, Kim WK, Bae KH. The Role of Adipose Tissue Mitochondria: Regulation of Mitochondrial Function for the Treatment of Metabolic Diseases. Int J Mol Sci. 2019 Oct 4;20(19):4924. doi: 10.3390/ijms20194924. PMID: 31590292; PMCID: PMC6801758.

(6) Bournat JC, Brown CW. Mitochondrial dysfunction in obesity. Curr Opin Endocrinol Diabetes Obes. 2010 Oct;17(5):446-52. doi: 10.1097/MED.0b013e32833c3026. PMID: 20585248; PMCID: PMC5001554.

(7) Patrick J Ferrara, Marisa J Lang, Jordan M Johnson, Shinya Watanabe, Kelsey L McLaughlin, John Alan Maschek, Anthony R P Verkerke, Piyarat Siripoksup, Amandine Chaix, James E Cox, Kelsey H Fisher-Wellman, Katsuhiko Funai, Weight loss increases skeletal muscle mitochondrial energy efficiency in obese mice, Life Metabolism, Volume 2, Issue 2, April 2023, load014, https://doi.org/10.1093/lifemeta/load014

(8) Breininger SP, Malcomson FC, Afshar S, Turnbull DM, Greaves L, Mathers JC. Effects of obesity and weight loss on mitochondrial structure and function and implications for colorectal cancer risk. Proc Nutr Soc. 2019 Aug;78(3):426-437. doi: 10.1017/S0029665119000533. Epub 2019 Mar 22. PMID: 30898183; PMCID: PMC6685789.

CELLULAR SENESCENE

(1) Conley Sabena M., Hickson LaTonya J., Kellogg Todd A., McKenzie Travis, Heimbach Julie K., Taner Timucin, Tang Hui, Jordan Kyra L., Saadiq Ishran M., Woollard John R., Isik Busra, Afarideh Mohsen, Tchkonia Tamar, Kirkland James L., Lerman Lilach O. Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells. Frontiers in Cell and Developmental Biology. VOL 8. 2020. DOI=10.3389/fcell.2020.00197. ISSN=2296-634X

(2) Rosa Spinelli,1,2,3 Ritesh Kumar Baboota,1,4 Silvia Gogg,1 Francesco Beguinot,2,3 Matthias Blüher,5 Annika Nerstedt,1 and Ulf Smith1. Increased cell senescence in human metabolic disorders. JCI. Published June 15, 2023

(3) Xu M, Palmer AK, Ding H, Weivoda MM, Pirtskhalava T, White TA, Sepe A, Johnson KO, Stout MB, Giorgadze N, Jensen MD, LeBrasseur NK, Tchkonia T, Kirkland JL. Targeting senescent cells enhances adipogenesis and metabolic function in old age. Elife. 2015 Dec 19;4:e12997. doi: 10.7554/eLife.12997. PMID: 26687007; PMCID: PMC4758946.

(4) Narasimhan A, Flores RR, Camell CD, Bernlohr DA, Robbins PD, Niedernhofer LJ. Cellular Senescence in Obesity and Associated Complications: a New Therapeutic Target. Curr Diab Rep. 2022 Nov;22(11):537-548. doi: 10.1007/s11892-022-01493-w. Epub 2022 Oct 14. PMID: 36239841; PMCID: PMC10123542

STEM CELL EXHAUSTION

(5) Conley Sabena M., Hickson LaTonya J., Kellogg Todd A., McKenzie Travis, Heimbach Julie K., Taner Timucin, Tang Hui, Jordan Kyra L., Saadiq Ishran M., Woollard John R., Isik Busra, Afarideh Mohsen, Tchkonia Tamar, Kirkland James L., Lerman Lilach O. Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells. Frontiers in Cell and Developmental Biology. VOL 8. 2020.

(6) Oestreich AK, Collins KH, Harasymowicz NS, Wu CL, Guilak F. Is Obesity a Disease of Stem Cells? Cell Stem Cell. 2020 Jul 2;27(1):15-18. doi: 10.1016/j.stem.2020.04.019. PMID: 32619511; PMCID: PMC8715393.

(7) Mihaylova MM, Sabatini DM, Yilmaz ÖH. Dietary and metabolic control of stem cell function in physiology and cancer. Cell Stem Cell. 2014 Mar 6;14(3):292-305. doi: 10.1016/j.stem.2014.02.008. PMID: 24607404; PMCID: PMC3992244.

ALTERED INTERCELLULAR COMMUNICATION

(1) Shamsi, F., Zheng, R., Ho, LL. et al. Comprehensive analysis of intercellular communication in the thermogenic adipose niche. Commun Biol 6, 761 (2023). https://doi.org/10.1038/s42003-023-05140-2

(2) Berumen Sánchez G, Bunn KE, Pua HH, Rafat M. Extracellular vesicles: mediators of intercellular communication in tissue injury and disease. Cell Commun Signal. 2021 Oct 16;19(1):104. doi: 10.1186/s12964-021-00787-y. PMID: 34656117; PMCID: PMC8520651.

(3) Schmidt AM (2023) Obesity research: Moving from bench to bedside to population. PLoS Biol 21(12): e3002448. https://doi.org/10.1371/journal.pbio.3002448

CHRONIC INFLAMMATION

(4) Khanna D, Khanna S, Khanna P, Kahar P, Patel BM. Obesity: A Chronic Low-Grade Inflammation and Its Markers. Cureus. 2022 Feb 28;14(2):e22711. doi: 10.7759/cureus.22711. PMID: 35386146; PMCID: PMC8967417.

(5) Hildebrandt, X., Ibrahim, M. & Peltzer, N. Cell death and inflammation during obesity: “Know my methods, WAT(son)”. Cell Death Differ 30, 279–292 (2023). https://doi.org/10.1038/s41418-022-01062-4

(6) Sarin, H.V., Lee, J.H., Jauhiainen, M. et al. Substantial fat mass loss reduces low-grade inflammation and induces positive alteration in cardiometabolic factors in normal-weight individuals. Sci Rep 9, 3450 (2019). https://doi.org/10.1038/s41598-019-40107-6

(7) Chait Alan, den Hartigh Laura J. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Frontiers in Cardiovascular Medicine. VOL 7. 2020.

DISABLED MACROPHAGE AUTOPHAGY

(1) H. J. Jansen, P. van Essen, T. Koenen, L. A. B. Joosten, M. G. Netea, C. J. Tack, R. Stienstra, Autophagy Activity Is Up-Regulated in Adipose Tissue of Obese Individuals and Modulates Proinflammatory Cytokine Expression, Endocrinology, Volume 153, Issue 12, 1 December 2012, Pages 5866–5874, https://doi.org/10.1210/en.2012-1625

(2) Namkoong S, Cho CS, Semple I, Lee JH. Autophagy Dysregulation and Obesity-Associated Pathologies. Mol Cells. 2018 Jan 31;41(1):3-10. doi: 10.14348/molcells.2018.2213. Epub 2018 Jan 23. PMID: 29370691; PMCID: PMC5792710.

(3) Castañeda, D., Gabani, M., Choi, S.-K., Nguyen, Q.M., Chen, C., Mapara, A., Kassan, A., Gonzalez, A.A., Ait-Aissa, K. and Kassan, M. (2019), Targeting Autophagy in Obesity-Associated Heart Disease. Obesity, 27: 1050-1058. https://doi.org/10.1002/oby.22455

(4) Ro Seung-Hyun, Jang Yura, Bae Jiyoung, Kim Isaac M., Schaecher Cameron, Shomo Zachery D. Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity. Frontiers in Physiology. VOL 10. 2019.

DYSBIOSIS

(5) Zhong X, Harrington JM, Millar SR, Perry IJ, O’Toole PW, Phillips CM. Gut Microbiota Associations with Metabolic Health and Obesity Status in Older Adults. Nutrients. 2020 Aug 7;12(8):2364. doi: 10.3390/nu12082364. PMID: 32784721; PMCID: PMC7468966.

(6) Breton J, Galmiche M, Déchelotte P. Dysbiotic Gut Bacteria in Obesity: An Overview of the Metabolic Mechanisms and Therapeutic Perspectives of Next-Generation Probiotics. Microorganisms. 2022 Feb 16;10(2):452. doi: 10.3390/microorganisms10020452. PMID: 35208906; PMCID: PMC8877435.

(7) Ghosh, T.S., Shanahan, F. & O’Toole, P.W. Toward an improved definition of a healthy microbiome for healthy aging. Nat Aging 2, 1054–1069 (2022). https://doi.org/10.1038/s43587-022-00306-9

(8) Koutoukidis DA, Jebb SA, Zimmerman M, Otunla A, Henry JA, Ferrey A, Schofield E, Kinton J, Aveyard P, Marchesi JR. The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis. Gut Microbes. 2022 Jan-Dec;14(1):2020068. doi: 10.1080/19490976.2021.2020068. PMID: 35040746; PMCID: PMC8796717.

(9) Jian, C., Silvestre, M.P., Middleton, D. et al. Gut microbiota predicts body fat change following a low-energy diet: a PREVIEW intervention study. Genome Med 14, 54 (2022). https://doi.org/10.1186/s13073-022-01053-7

The Role of 'Healthy Body Weight Spray' in Fat Loss

Harnessing the Power of Fat Loss

Introducing the cornerstone of our age-reversal arsenal – the Healthy Body Weight Spray. This potent tool is engineered to help shed years off your cellular age while supporting your weight management journey.

HARNESSING THE POWER OF FAT LOSS

TESTIMONIALS

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SMART FITNESS LABS’ HEALTHY BODY WEIGHT SPRAY

1 oz. bottle of Smart Fitness Labs’ Healthy Body Weight Formula Dietary Supplement

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