The development of ageing-related diseases seems to be closely related to the extent of damage inflicted on the cells by oxidative stress. Researchers define oxidative stress as damage to proteins, nucleic acids, and lipids caused by an imbalance between harmful reactive oxygen species (frequently referred to as free radicals) and the body’s antioxidative defenses [Alehagen 2021].
A 2021 review of the relevant research literature reveals the following findings [Alehagen 2021]:
-Optimal selenium status is necessary for the synthesis of the antioxidant seleno-enzymes: the glutathione peroxidases and the thioredoxin reductases.
-Selenium deficiency in elderly individuals seems to increase the risk of developing age-related diseases: chronic inflammation, cardiovascular disease, cancer, and neurodegenerative diseases.
-Selenium supplementation to achieve optimal selenium status may help to remodel bio-chemical and physiological changes that accompany ageing:
- improving immune function
- mediating metabolic homeostasis
- providing antioxidant defense
- alleviating heavy metal toxicity [Alehagen 2021].
Benefits of Adequate Selenium Status in the Elderly
- Adequate selenium status appears to affect positively the self-image with respect to health, physical activity, and quality of life [Gonzalez 2007; Johansson 2015].
- Adequate selenium status has been reported to protect against the development of cardiovascular disease [Al-Mubarak 2021; Alehagen 2013; Kuria 2020 ].
- Higher selenium status has been associated with higher cure-rates and lower death-rates in individuals infected with Covid-19, a disease in which the lethality increases strongly with age [Zhang 2020].
- A 2020 meta-analysis shows that selenium is protective against cancer; the effects may vary according to the type of cancer [Kuria 2020].
Selenium and Ageing: Bio-Chemical Mechanisms
Chronic inflammation and oxidative stress
It appears that oxidative stress, inflammation, and ageing interact with one other in complex ways. Chronic inflammation in the elderly represents a risk factor for several diseases including cancer, cardiovascular disease, and dementia [Alehagen 2021].
Supplementation with selenium seems to enhance antioxidant capacity and to alleviate inflammation [Hariharan 2017].
In the Swedish KiSel-10 clinical trial, supplementation with a combination of organic selenium and Coenzyme Q10 was associated with an enhancement of antioxidant capacity and alleviation of inflammation [Alehagen 2018].
Cardiovascular disease
In the BIOSTAT-CHF prospective observational cohort study, heart failure patients deficient in selenium (defined as serum selenium status below 70 mcg/L) had worse New York Heart Association (NYHA) functional class, more severe signs of heart failure, less exercise capacity, and lower quality of life than heart failure patients with higher plasma selenium. Selenium deficiency was also associated with higher rate of hospitalization for heart failure or all-cause mortality. Heart failure patients with serum selenium status between 70 and 100 mcg/L had similar adverse associations; this suggests that serum selenium status below 100 mcg/L, might be considered abnormal [Bomer 2020].
Researchers in the Malmö Preventive Project, a prospective cohort study including 4366 individuals that were followed for 9.3 (8.3-11) years, determined plasma selenoprotein-P concentrations and concluded that the risk of all-cause mortality, cardiovascular mortality, and a first cardiovascular event were all inversely associated with the plasma selenoprotein-P concentration [Schomburg 2019].
In the KiSel-10 Trial, researchers observed a significantly reduced cardiovascular disease mortality in elderly study participants (> 70 years) who were supplemented with 200 mcg selenium/day for four years. The mean baseline plasma selenium concentration in the KiSel-10 trial was quite low: 67.1 mcg/L [Alehagen 2013].
Neurodegenerative diseases
Ageing would seem to be the most significant risk factor for developing Alzheimer’s disease and Parkinson’s disease.
Oxidative stress and mitochondrial dysfunction have been proposed as causative links between ageing and neurodegenerative diseases [Alehagen 2021].
Antioxidative selenoenzymes defend against oxidative stress; consequently, sub-optimal selenium status may increase the risk of developing these disorders [Aaseth 2016]. Elevated free radical levels may play a role in the pathologies of Alzheimer’s disease and Parkinson’s disease [Alehagen 2021].
Cancer
Epidemiological studies conducted in Europe, the USA, China, and Japan have shown a significant protective role of selenium in cancer [Alehagen 2021].
Deficient intake of selenium seems to be associated with an increased risk of certain cancers in elderly people. The link may be the lesser protection against oxidative stress and inflammation associated with low selenium status. However, the mechanisms of selenium protection against cancer are not yet known [Alehagen 2021].
A 2020 meta-analysis concluded that daily selenium intakes above 55 mcg/day were associated with decreases in the risk of cancer [Kuria 2020].
Reduced renal function
Low selenium and selenoprotein P status seem to be associated with reduced renal function [Reinhardt 2015]. Elderly individuals often suffer glomerular or tubular dysfunction and manifest renal failure [Aaseth 2021; Denic 2016].
Combined supplementation with selenium and Coenzyme Q10 has been shown to improve renal function in elderly individuals deficient in selenium [Alehagen 2020].
Bottom Line: Selenium and Ageing
Biological ageing is a complex process involving molecular damage, metabolic imbalance, and changes in immune function, resulting increased susceptibility to diseases and environmental stresses.
Deficiency in selenium is closely associated with human ageing and ageing-associated diseases.
The mechanisms related to selenium deficiency and ageing are free radical associated oxidative damage and chronic inflammation.
Dietary and supplemental selenium is an important nutritional agent in the protection against age-related diseases that are mediated via the immune response.
There is still conflicting evidence regarding a relationship between selenium intake and status and cancer and cardiovascular disease.
With respect to the development of cancer, it seems that a deficient intake of selenium with the subsequent inadequate synthesis of functional selenoproteins and less protection against oxidative stress and inflammation plays an important role.
Dietary intakes of selenium vary considerably from region to region in the world, depending upon the content of selenium in the soil and in the food.
The estimate for optimal health benefit of selenium is plasma/serum selenium status of 125 mcg/L [Rayman 2020].
Sources
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Aaseth J, Alexander J, Alehagen U, et al. The Aging Kidney-As Influenced by Heavy Metal Exposure and Selenium Supplementation. Biomolecules. 2021;11(8):1078.
Alehagen U, Opstad TB, Alexander J, Larsson A, Aaseth J. Impact of selenium on biomarkers and clinical aspects related to ageing: A review. Biomolecules. 2021;11(10):1478.
Alehagen U, Aaseth J, Alexander J, Brismar K, Larsson A. Selenium and Coenzyme Q10 supplementation improves renal function in elderly deficient in selenium: observational results and results from a subgroup analysis of a prospective randomised double-blind placebo-controlled trial. Nutrients. 2020 Dec 9;12(12):3780.
Alehagen U, Aaseth J, Alexander J, Johansson P. Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly. PLoS ONE. 2018;13:e0193120.
Alehagen U, Johansson P, Björnstedt M, Rosén A, Dahlström U. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Int J Cardiol. 2013 Sep 1;167(5):1860-6.
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The information contained in this review article is not intended as medical advice and should not be used as such.
15 October 2021