You may have heard the term geroprotective supplements for the first time.
But what are they?
Under this name we can group a wide range of options that, in the form of supplements, have been shown to have verified actions on the complex mechanisms of aging.

Aging

Ageing is a topic that has always been talked about, especially the fight against it and the promotion of good health. At Salengei we prefer to accompany aging from another point of view; we want to ensure that the passage of time is lived in a natural way, preventing those diseases that are possible and achieving a fuller life.

Cellular senescence is one of the most important in vivo mechanisms related to aging. Senescent cells limit tissue function through irreparable cell damage resulting from acute stress or natural aging, restricting life expectancy inexorably.
Cellular senescence can be classified into two groups.

Replicative senescence, observed after approximately sixty rounds of cell division in cultures (Hayflick’s limit), results from the progressive erosion of telomeres after each division.
This progressive erosion leads to telomere dysfunction and irreversible cell cycle arrest.

The second category is defined as premature cellular senescence and is related to persistent cellular stress.
Thus, replicative stress caused by oxidative DNA damage, oncogene activation, and loss of tumor suppressor genes also results in premature senescence.
In addition, premature senescence includes the irreversible impairment of the reproductive capacity of tumor cells through chemo or radiation therapy-induced apoptosis, which is defined as drug- or radiation-induced senescence.
Stress-induced premature senescence of normal cells in vivo is considered a critical mechanism affecting aging and longevity of the organism.

Geroprotective supplements

Geroprotectants are a series of substances that have been shown to act on the molecular factors of aging.
If you are a reader of our blog, you will know that we have already addressed some of them in our articles.
Others are medicinal substances – which are beyond our objectives – that have added beneficial effects to those already known, as is the case of metformin.

In recent years, numerous geroprotectants, senolytics, and nutraceuticals have emerged as potential disruptors of aging and could be viable interventions in terms of human longevity.
The doubling of life expectancy in the last century can be attributed to progressive advances in health and clinical care for the human population.
However, at the expense of longevity comes an increased risk of age-related diseases.
As the main risk factor for the increasing incidence of neurodegenerative, cardiovascular, cancer, and other chronic diseases, aging has come to the fore as a new clinical target in itself, with the aim of serving as a preventive measure for the development of such diseases.
DOI: 10.1016/j.cub.2012.07.024

To put it a little drastically, aging can be characterized as a universal, intrinsic, progressive deterioration that is harmful to the health of the individual.
A multimodal attack on the body’s physiological processes, whether through environmental damage, a decrease in endogenous protective mechanisms, or a breakdown of the physiological process due to natural wear and tear.

Targeting the characteristics of aging as a model of action would allow interventions that improve these processes, such as genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, dysregulated detection of nutrients, mitochondrial dysfunction, cellular senescence, stem cell depletion and altered intercellular communication. It is believed that each intervention focused on these characteristics could have a multimodal cross-effect that would enhance the biological processes of aging. DOI: 10.1016/j.tem.2014.08.003

Appropriate, widespread and easily implemented interventions are key factors in combating the newly defined epidemic of ageing and age-related disorders. The use of supplementation as a therapeutic approach to slow down the aging process is of great application when selecting and formulating geroprotective treatments. Longevity supplements have shown great potential to boost health, and research on longevity supplements is one of the fastest advancing fields of aging science today. https://doi.org/10.1038/sj.ejcn.1602438

Resveratrol

One of the most studied nutraceuticals is the phenolic compound non-flavonoid stilbene, better known as resveratrol.
This compound, which is naturally found in grapes and berries, possesses a host of anti-inflammatory and antioxidant characteristics, and may even combat many age-related disorders.

While resveratrol may have many other targets, experimental models have demonstrated a close association with the SIRT1 pathway when investigating dosage and supplementation.
Resveratrol has shown many health benefits, but it has yielded mixed results when used specifically for the treatment of diseases.

This agent appears to be involved at least indirectly in activating SIRT1 to induce the beneficial effects of calorie restriction, which has been shown numerous times to induce a lifespan extension.
The activation of SIRT1 together with AMPK and PGC1α in response to resveratrol is implicated, but more studies are still needed.
Even so, resveratrol could be considered an age-related metabolic modulator.
https://doi.org/10.1155/2021/9932218

The imitation of caloric restriction would occur through several mechanisms.
First, increase telomerase and FoxO3a activity, a transcription factor associated with increased longevity.
Also, through the active regulation of Sirt1 (AROS).
Finally, increasing the Hu R antigen (HuR) and decreasing p53 may prevent cellular senescence, but inhibit tumor suppression. https://doi.org/10.3390/cancers14112666

Resveratrol may also enhance neuroprotection by reducing neuroinflammation, thereby improving cognition and neurometabolic protection and decreasing the risk of age-related neurodegeneration.
In addition, it possesses the ability to enhance oxidative stress in the vasculature by reducing superoxide generation and increasing the antioxidant response of endothelial cells, thereby dissipating the risk of age-related cardiovascular disease, also initiated through the pathway involved in SIRT1.

Cognitive decline due to aging was attenuated by improved cognitive performance in older mice and decreased levels of inflammatory mediators such as IL-1β and TNF-α in response to resveratrol, and aged mice given resveratrol showed improvements in cerebrovascularity.
In response to a high-fat diet in rats, resveratrol or alpha-ketoglutarate (aKG) improved brain and metabolic aging profiles, especially through inflammatory response genes. https://doi.org/10.31883/pjfns/139081

Witte et al., 2014, looked at the administration of resveratrol at 200 mg daily in older adults to affect memory performance, hippocampal connectivity, and glucose metabolism. The results were that memory retention increased in the interventionist group, along with greater functional connectivity in the frontal, parietal, and occipital regions of the hippocampus.
Hemoglobin A1c (HB1Ac) and body fat decreased, implying a reduction in blood sugar, and the satiety hormone, leptin, increased.
Both changes correlated with higher memory retention and greater functional connectivity.
These changes were consistent with the benefits reported in previous studies, further demonstrating improved cognitive function and improved metabolic profiles through resveratrol supplementation. https://doi.org/10.1523/JNEUROSCI.0385-14.2014

In the context of patients with neurodegeneration and Alzheimer’s disease with mild impairment, treatment with resveratrol resulted in a decrease in the neuroinflammatory profile and MMP9 expression, but more studies are still needed to validate the mechanism and efficacy in neurodegenerative disorders. https://doi.org/10.1186/s12974-016-0779-0

Interestingly, the administration of resveratrol has been quite beneficial in improving postmenopausal symptoms in older women.
A 24-month crossover study in 125 postmenopausal women showed marked improvements in cognition, cerebrovascular function, and insulin sensitivity, and sustained cognitive, cardiovascular, and cerebrovascular benefits were reported over a 12-month study period in response to the same daily treatment with doses of 75mg. https://doi.org/10.3390/nu12030828

Berberine

Berberine is a primary active ingredient isolated from the root and bark of the rhizome of Coptidis, a traditional herb of Traditional Chinese Medicine.
It has long been used as an over-the-counter medication to treat gastrointestinal infections, such as bacillary dysentery.
Due to its multi-drug effects on a wide spectrum of age-related diseases, such as hypertension, hyperlipidemia and Alzheimer’s disease, it has been proposed as an attractive “elixir of eternal life” to combat ageing.

Most components of berberine, including coptisin, palmatin, and jatrorrhizin, have been found to have beneficial effects on hyperlipidemia, hyperglycemia, and hypertension in aging-related diseases.
The mechanism of these effects involves multiple cellular kinases and signaling pathways, including anti-oxidation, activation of AMPK signaling, and its downstream targets, including mTOR/rpS6, Sirtuin1/forkhead box transcription factor O3 (FOXO3), erythroid-related nuclear factor-2 (Nrf2), NAD+, and nuclear factor-κB (NF-κB) pathway.
Most of these mechanisms converge in the regulation of AMPK on mitochondrial oxidative stress.
Therefore, such evidence supports the possibility that berberine is a promising natural anti-aging product and has pharmaceutical potential to combat aging-related diseases through anti-oxidation and activation of the cellular kinase AMPK.
DOI: 10.14336/AD.2016.0620

In several model ageing/senescence systems, such as the diploid fibroblasts of the fetal lung of the Drosophila fly and in mice, berberine has readily demonstrated an anti-senescence or life-prolonging function.
In addition, it was hypothesized that berberine, with potential anti-aging effects, could treat senescence in aging cells. https://doi.org/10.1016/B978-0-12-823679-6.00020-5

As aging is a multifaceted process, it is likely that an anti-aging drug is related to multiple processes. Specifically, berberine would negatively regulate p16 and positively regulate the expression of cyclin D1 and CDK4, promoting cell cycle progression.
In addition, it was observed that berberine’s protective effect against aging could be related to its effect on the expression of p16, RB, cyclin protein, and their specific kinases. https://doi.org/10.1111/acel.13060

Salengei Products

Numerous articles talk about the possibilities of being able to live a long and healthy life through the improvement of our habits, effective supplementation and specific modifications that are not complicated to make.

At Salengei we offer supplements made from assets from certified sources that have the best quality on the market.
Because we are aware that taking any supplement is not the same as taking one that contains the right amounts and comes from the best suppliers.

On our website you can access more information about Active Resveratrol and Active Berberine.

Conclusion

In the present article, we have established the benefits of two ingredients involved in longevity-related pathways in the context of supplementation for healthy aging.
Many ingredients alone show numerous benefits in the realm of many age-related disorders, such as neurodegeneration, cardiovascular and metabolic diseases, diabetes, and cancer.

A beneficial direction could be to further investigate other geroprotectants and senolytics that improve numerous characteristics of aging.
Further clarification of SIRT1 activity is required, for example, in relation to the downstream effects involved in longevity extensions shown in experimental models, particularly in humans, to determine the maximum effect through nutraceutical interventions.

The potential of knowledge generated from a deeper analysis of these relationships within the context of human ageing may offer insights into other pathways that may be involved in longevity.
In addition, avenues may emerge to address the pathology of aging and age-related diseases to increase life expectancy after further exploration of other geroprotectants, particularly in clinical trials.

By looking for compounds that show an effect on molecular pathways related to aging, innovative formulations of geroprotective ingredients can be achieved.

Perhaps the maximum benefit can be derived not simply from one compound but from an ingredient profile that incorporates multiple compounds that work together to achieve a synergistic effect.