Aging and senescence: approach from apitherapy

In recent decades there has been an increase in the world population and life expectancy. During the last century the world population quadrupled and estimates indicate that in the next decades it will double again (1). Likewise, life expectancy has been shown to increase significantly, before 1800 it was 32 years old, in countries like Sweden by 1900 it was 50 years old and it is currently estimated at 82 years (2 ,3).

Demographic dynamics, changing according to populations, show different scenarios, according to birth rates, mortality and life expectancy. Developed countries generally show low birth rates and a higher life expectancy, which leads to a population that is over 40 years of age. Of course, many countries are still in this transition process (4,5). This, in addition to technological, medical advances and improvement in people’s living conditions, has modified the profile of diseases that occur in populations (6,7). That is, there is an increasingly aging population worldwide.

There are some approaches to the concept of aging. Aging has been defined as that process that leads to persistent deterioration in the components that are responsible for maintaining the natural state of the body due to physiological deterioration (8). It has also been defined as the process of progressive deterioration of physiological function that leads to an increase in age-dependent mortality (9). There are several important elements that arise from these definitions: functional capacity, onset of diseases and age-dependent mortality. They then define aging as a stage of life however it is clear that it does not start at the same chronological age (years old) in all people.

In a recent investigation it was tried to evaluate the age at which the process of aging of the body begins by measuring the activity and expression of various proteins related to aging, being evident that on average 34 years is the age at which it begins (10). There is of course in some cases the mismatch between the chronological age and the biological age, that is the identifiable age according to the state of the body. The evaluation of mitochondrial and nuclear DNA methylations is a method currently used to assess aging and serves as a predictor of mortality (11). Premature aging deteriorates the quality of life and is related to the development of various diseases and their outcomes (12).

Biological processes involved in aging


There are several theories that try to explain the origin of aging. These can be classified into three groups: deterministic (only by studying the genes is it possible to explain aging, for example), stochastic (various random factors explain aging) and mixed theories (13). The truth is that only by combining various physiological and pathological processes is it possible to explain all the events that occur in aging. Next, several of the processes involved in the aging process are addressed:

Genetic factors. The processes of cell division over time, exposure to trauma, allostatic overload and chemical and physical agents leads to the development of mutations in the DNA that alter cellular functioning (14). The study of the progreria has allowed to identify genes of relevance in the explanation of aging:

Shortening of telomeres. Telomeres give stability to genetic information and over time they become progressively and significantly shortened. This process is related to the speed with which aging occurs (15). It has also been established that a smaller telomere size is related to a higher mortality from all causes (16).

Mitochondrial DNA injury. Mitochondrial DNA lesions resulting from the action of free radicals, accumulated mutations throughout life and alterations in the processes of fusion and mitochondrial fission are related to biological age, shorter telomere length and phenotypic changes. of aging (17).

Hyperactivation of the nuclear factor Kappa Beta. Senescent cells show exaggerated activation of the nuclear factor Kappa Beta which leads to functional loss and destruction of tissues and systemic inflammation (18).

Free radicals. Free radicals are involved in aging by the induction of cell death they produce, the generation of mutations and functional alteration (19).

Cross junctions of cellular structures. The glycation processes affect cell structures, modify the extracellular matrix and affect the function of organs and tissues. These processes are related to a higher aging rate (20).

Immune system. With the increase of age there are many senescent immune system cells. This causes a decrease in the repertoire of B and T cells, a decrease in their response and alterations in the release of cytokines necessary for communication with other cell groups (21).

Epigenetics. Methylation processes affect the nucleosome and the way in which DNA is stored by altering the expression of different proteins. Greater methylation is related in turn to the speed with which aging occurs (22).

Use of apitherapy in anti aging

The Beehive products are very useful in the aging process. There are several mechanisms through which they act:

Bibliographic references

1.          Vilches A., Gil Pérez D., Toscano J.C., Macías O. Crecimiento demográfico y Sostenibilidad. Oei. 2018.

2.          Herce JA. El impacto del envejecimiento de la población en España. Cuad Inf Económica. 2016;

3.          Bezrukov V, Foigt NA. Longevidad centenaria en Europa. Revista Espanola de Geriatria y Gerontologia. 2005.

4.          Miró G. C. Transición demográfica y envejecimiento demográfico. Papeles de población. 2003;

5.          Chackiel J. La dinámica demográfica en América Latina. Población y Desarro. 2004;

6.          Luis Arredondo García J, Nora Carranza Rodríguez M, Margarita Vázquez Cruz Q, Ángel Rodríguez Weber M. Transición epidemiológica. Acta Pediatr Méx. 2003.

7.          Ramos-Clason EC. Transición epidemiológica en Colombia: de las enfermedades infecciosas a las no transmisibles. Rev Ciencias Biomédicas. 2012;

8.          Galloway A. The evolutionary biology of aging. By Michael R. Rose. New York: Oxford University Press. 1991. ix + 221 pp. ISBN 0-19-506133-0. $35.00 (cloth). Am J Phys Anthropol [Internet]. 1993 Jun;91(2):260–2. Available from: http://doi.wiley.com/10.1002/ajpa.1330910217

9.          Fabian DK, Flatt T. The evolution of Aging. Nat Educ Knowl. 2011;3(10):9.

10.        Lehallier B, Gate D, Schaum N, Nanasi T, Lee SE, Yousef H, et al. Undulating changes in human plasma proteome profiles across the lifespan. Nat Med [Internet]. 2019 Dec 5;25(12):1843–50. Available from: http://www.nature.com/articles/s41591-019-0673-2

11.        Jazwinski SM, Kim S. Metabolic and Genetic Markers of Biological Age. Front Genet [Internet]. 2017 May 23;8. Available from: http://journal.frontiersin.org/article/10.3389/fgene.2017.00064/full

12.        Seco M, B. Edelman JJ, Forrest P, Ng M, Wilson MK, Fraser J, et al. Geriatric Cardiac Surgery: Chronology vs. Biology. Hear Lung Circ [Internet]. 2014 Sep;23(9):794–801. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1443950614001814

13.        Semsei I. On the nature of aging. Mech Ageing Dev [Internet]. 2000 Aug;117(1–3):93–108. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0047637400001470

14.        Ren J, Zhang Y. Genetics and Epigenetics in Aging and Longevity: Myths and Truths. Biochim Biophys Acta – Mol Basis Dis [Internet]. 2019 Jul;1865(7):1715–7. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0925443919300572

15.        Rizvi S, Raza ST, Mahdi F. Telomere Length Variations in Aging and Age-Related Diseases. Curr Aging Sci [Internet]. 2015 Mar 2;7(3):161–7. Available from: http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1874-6098&volume=7&issue=3&spage=161

16.        Arbeev KG, Verhulst S, Steenstrup T, Kark JD, Bagley O, Kooperberg C, et al. Association of Leukocyte Telomere Length With Mortality Among Adult Participants in 3 Longitudinal Studies. JAMA Netw Open [Internet]. 2020 Feb 26;3(2):e200023. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2761863

17.        Dolcini J, Wu H, Nwanaji-Enwerem JC, Kiomourtozlogu M-A, Cayir A, Sanchez-Guerra M, et al. Mitochondria and aging in older individuals: an analysis of DNA methylation age metrics, leukocyte telomere length, and mitochondrial DNA copy number in the VA normative aging study. Aging (Albany NY) [Internet]. 2020 Feb 2;12(3):2070–83. Available from: http://www.aging-us.com/article/102722/text

18.        Tornatore L, Thotakura AK, Bennett J, Moretti M, Franzoso G. The nuclear factor kappa B signaling pathway: integrating metabolism with inflammation. Trends Cell Biol [Internet]. 2012 Nov;22(11):557–66. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0962892412001407

19.        Davinelli S, Bertoglio JC, Polimeni A, Scapagnini G. Cytoprotective Polyphenols Against Chronological Skin Aging and Cutaneous Photodamage. Curr Pharm Des [Internet]. 2018 Apr 5;24(2):99–105. Available from: http://www.eurekaselect.com/156953/article

20.        Simm A, Müller B, Nass N, Hofmann B, Bushnaq H, Silber R-E, et al. Protein glycation — Between tissue aging and protection. Exp Gerontol [Internet]. 2015 Aug;68:71–5. Available from: https://linkinghub.elsevier.com/retrieve/pii/S053155651400360X

21.        Sadighi Akha AA. Aging and the immune system: An overview. J Immunol Methods [Internet]. 2018 Dec;463:21–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022175917304878

22.        Pal S, Tyler JK. Epigenetics and aging. Sci Adv [Internet]. 2016 Jul 29;2(7):e1600584. Available from: https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.1600584

23.        Gu SM, Park MH, Hwang CJ, Song HS, Lee US, Han SB, et al. Bee venom ameliorates lipopolysaccharide-induced memory loss by preventing NF-kappaB pathway. J Neuroinflammation [Internet]. 2015 Dec 26;12(1):124. Available from: http://www.jneuroinflammation.com/content/12/1/124

24.        Cai M, Lee JH, Yang EJ. Bee Venom Ameliorates Cognitive Dysfunction Caused by Neuroinflammation in an Animal Model of Vascular Dementia. Mol Neurobiol [Internet]. 2017 Oct 29;54(8):5952–60. Available from: http://link.springer.com/10.1007/s12035-016-0130-x

25.        Jang H-S, Kim SK, Han J-B, Ahn H-J, Bae H, Min B-I. Effects of bee venom on the pro-inflammatory responses in RAW264.7 macrophage cell line. J Ethnopharmacol [Internet]. 2005 May;99(1):157–60. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0378874105001996

26.        Kocyigit A, Guler EM, Kaleli S. Anti-inflammatory and antioxidative properties of honey bee venom on Freund’s Complete Adjuvant-induced arthritis model in rats. Toxicon [Internet]. 2019 Apr;161:4–11. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0041010119300571

27.        Hozzein WN, Badr G, Badr BM, Allam A, Ghamdi A Al, Al-Wadaan MA, et al. Bee venom improves diabetic wound healing by protecting functional macrophages from apoptosis and enhancing Nrf2, Ang-1 and Tie-2 signaling. Mol Immunol [Internet]. 2018;103:322–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/30366166

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29.        Lee E-J, Kang M-K, Kim D, Kim Y-H, Oh H, Kang Y-H. Chrysin Inhibits Advanced Glycation End Products-Induced Kidney Fibrosis in Renal Mesangial Cells and Diabetic Kidneys. Nutrients [Internet]. 2018 Jul 9;10(7):882. Available from: http://www.mdpi.com/2072-6643/10/7/882

30.        Cruz LC, Ecker A, Rodrigues NR, Martins IK, Posser T, Maciel FE, et al. Honey protects against wings posture error and molecular changes related to mitochondrial pathways induced by hypoxia/reoxygenation in adult Drosophila melanogaster. Chem Biol Interact [Internet]. 2018 Aug;291:245–52. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0009279717313509

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