Personalized, Consistent Exercise as a Preventive and Therapeutic Approach to Healthy Longevity

In the Italian Senate, a bill is being drafted to make physical activity prescribable as a therapy within the National Health Service (SSN). The guiding principle with which work is proceeding is to formally recognize exercise as a component of prevention and treatment pathways in healthcare. If this measure is completed, it would certainly be a forward‑looking decision that could, over time, improve healthy longevity and reduce healthcare expenditures.

There is now a substantial body of scientific literature supporting the idea that regular physical activity, tailored to age and health status of individuals, is a fundamental tool for preventing and treating chronic diseases and psychological disorders, and, therefore, treating exercise—with personalized programs for each person—as a medicine is undeniably an excellent idea (1).

Regular physical activity has demonstrably improved human health by countering insulin resistance (IR) and by stimulating the production of myokines from contracting muscle (2–5).

It is well known that IR, widespread in the modern world, is in its own right an independent risk factor for the development of various diseases, and among the best known are type 2 diabetes and cardiovascular diseases. But there is ample evidence that IR is associated with cellular senescence, cancer, and neurodegenerative diseases as well (6).

Therefore, reducing IR through a therapy based on consistent physical activity could yield very important preventive results.

On the other hand, in recent years it has been discovered that skeletal muscle is not only responsible for movement, but is, in fact, an endocrine organ (7). In fact, contracting muscle releases myokines. These are special proteins produced and released by contracting skeletal muscles, particularly after longer-duration exercise, that exhibit autocrine, paracrine, and endocrine actions. Through myokines, the muscle can interact with other organs, such as the brain, the liver, the bones, and adipose tissue (8).

It has been shown that they confer numerous health benefits, having anti-inflammatory effects, reducing IR and thereby improving how the body handles sugars and fats, stimulating brain plasticity and improving mood and cognitive function, and supporting the immune system to help prevent several diseases. It is plausible that all these beneficial effects are also linked to a reduction in mortality. After all, consistent physical activity protects against the development of sarcopenia, which is a major driver of frailty and death in older adults (9).

These are only some of the important mechanisms, among many others, through which physical activity yields health benefits and reduces mortality (Figure 1).

Therefore, the welcome prospect of a law that formally recognizes physical activity as a fundamental component of prevention and treatment pathways is clear.

References

1. Istituto Superiore di Sanità. EpiCentro. L’epidemiologia per la sanità pubblica. Attività fisica. https://www.epicentro.iss.it/attivita_fisica/
2. Małkowska P. Positive Effects of Physical Activity on Insulin Signaling. Curr Issues Mol Biol. 2024 May 30;46(6):5467-5487. doi: 10.3390/cimb46060327. PMID: 38920999; PMCID: PMC11202552.
3. Kjøbsted R, Wojtaszewski JF, Treebak JT. Role of AMP-Activated Protein Kinase for Regulating Post-exercise Insulin Sensitivity. Exp Suppl. 2016;107:81-126. doi: 10.1007/978-3-319-43589-3_5. PMID: 27812978.
4. Severinsen MCK, Pedersen BK. Muscle-Organ Crosstalk: The Emerging Roles of Myokines. Endocr Rev. 2020 Aug 1;41(4):594–609. doi: 10.1210/endrev/bnaa016. Erratum in: Endocr Rev. 2021 Jan 28;42(1):97-99. doi: 10.1210/endrev/bnaa024. PMID: 32393961; PMCID: PMC7288608.
5. Pedersen BK. Physical activity and muscle-brain crosstalk. Nat Rev Endocrinol. 2019 Jul;15(7):383-392. doi: 10.1038/s41574-019-0174-x. PMID: 30837717.
6. Fazio S, Affuso F, Cesaro A, Tibullo L, Fazio V, Calabrò P. Insulin Resistance/Hyperinsulinemia as an Independent Risk Factor That Has Been Overlooked for Too Long. Biomedicines. 2024 Jun 26;12(7):1417. doi: 10.3390/biomedicines12071417. PMID: 39061991; PMCID: PMC11274573.
7. Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012 Apr 3;8(8):457-65. doi: 10.1038/nrendo.2012.49. PMID: 22473333.
8. Chen W, Wang L, You W, Shan T. Myokines mediate the cross talk between skeletal muscle and other organs. J Cell Physiol. 2021 Apr;236(4):2393-2412. doi: 10.1002/jcp.30033. Epub 2020 Sep 3. PMID: 32885426.
9. Martin FC, Ranhoff AH. Frailty and Sarcopenia. 2020 Aug 21. In: Falaschi P, Marsh D, editors. Orthogeriatrics: The Management of Older Patients with Fragility Fractures [Internet]. 2nd ed. Cham (CH): Springer; 2021. Chapter 4. PMID: 33347228.