As we have advocated several times on this site, that your primary care physician should be an active participant in this endeavor. Many of the labs we target below requires your physician to provide script to the laboratory in order to draw them.

Obviously, we want to see the markers move in the opposite direction that historical values normally move.  (See: “Correlates of Aging”) If a marker historically increases as we age, we want to see a small but noticeable decrease between our last lab draw and the most recent one. You should note that many of them peak between 65-80 years of age and then begin to decline again. This can produce the false impression that things are improving, when in fact your are seeing the results of normal aging. You should also be aware that many uncontrollable factors can impact these markers. Environmental contaminants; (dust, cigaret smoke, recreational drugs, alcohol, pesticides) emotional state including stress, sleep, mild to severe infections and changes in medications can all cause changes in any or all of the biomarkers we want to monitor. This makes it important that you monitoring protocol is maintained for as long as you are implementing aging interventions.

BASP is the difference between your chronological age, which is intransigent and inevitable, and the physiological / biological age of your immunological systems including organs, cells and chronokines. Clinical and laboratory biological markers are utilized to determine your current BASP.

Environmental factors like pollution, cigarets, alcohol, poor diet and any diseases process will move your BASP higher (older age). Exercise, good diet, meditation, sleep, socialization, friends, lovers, and family moves your BASP down (younger age).

Obviously targeted, biologically active, interventional modalities hold the potential to also regress you BASP. This site is dedicated to finding and optimizing the interventional strategies that safely allow for the reduction of your BASP. Targets of opportunity and agents that effectively and safely regress your BASP are emerging daily.

We have identified a minimal, yet effective set of markers and clinical observations that will provide you with relevant feedback on your progress in regressing you BASP score.

(1) ARC-BASP CORE BIOMARKERS

Expanding this core set of markers to include more expensive and more difficult to obtain BASP markers is of course desirable. The more information you have to guide and make decisions the more effective your path to effectively reducing your BASP will be.

We have provided five sets of markers that allow you to select and expand the amount of information you want or are able to obtain. Each marker is ranked as to its ease and expense of obtaining it and its relevance to effectively determine your BASP score.

The “E-Score,” is basically an ease of obtaining each biomarker and is scored on a scale of between 1 and 3. The system was adopted from the paper titled: “Ranking Biomarkers of Aging by Citation Profiling and Effort Scoring,” They describe this criteria as:

• A low e-score (1) describes a potential biomarker which is easy to sample, to handle and to process (usually automated fast and reliable measurements are available from known sources). For example, blood counts from venous blood qualify, since such blood can be sampled easily, the plasma/serum can be stored at room temperature (up to3 h for many analytes) or in a standard freezer (≥3 month for most analytes) and be processed by equipment that is regularly available in a standard diagnostic/clinical unit or research laboratory. The costs are low to moderate (≤10 €).

• A moderate e-score (2) is assigned if one step (sampling, handling, or processing) is associated with substantial extra effort for routine laboratories. This includes sampling under special conditions, a requirement for prompt sample handling, or the need for elaborate validation.

• A high e-score (3) implies elaborate sampling (e.g., biopsy, lumbar puncture, etc.), handling (e.g., storage in liquid nitrogen) and/or processing (e.g., non-routine nucleotide or protein sequencing). The financial costs are usually high.

Click [√] to Enlarge Image

CLICK [√] to Enlarge

This same group also attempted to provide a relevance score for each marker. This is simply a citation search of all published peer reviewed articles that contained the search criteria shown on the right. The field is moving so fast that some of the scores this process has generated no longer accurately reflect some indicators actual relevance. The authors freely admit that all of their scores are somewhat subjective.

These search results were then further divided into sub-categories. We have produced an excel spreadsheet that contains all of these markers including their RC-Scores and E-Scores that you can download by clicking on the “Excel” link below. We have annotated and added to the indicators provided and in some cases introducing new categories such as age determination by facial recognition. Finally we added our own ranking to denote the most effective and least expensive clinical/biomarkers of aging. Screenshots of each spreadsheet are available by clicking on the icon at the right of each biomarker category.

(1) Clinical, Physical Capability and Organ Function Biomarkers

(2) Routine Laboratory Biomarkers

(3) Research Laboratory Biomarkers (Non-epigenetic)

(4) Research Laboratory Biomarkers based on Epigenetic Measurements

(5) Visual Facial Age Recognition by AI

Complete Excel BioMarkers Spreadsheet is available by clicking on this image: > > >

Horvath’s DNA Methylation BASP Indicators

DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Recent research efforts provided compelling evidence of genome-wide DNA methylation alterations in aging and age-related disease. It is currently well established that DNA methylation biomarkers can determine biological age of any tissue across the entire human lifespan, even during development. [1]

Steve Horvath’s group, using large scale validation data from thousands of individuals, we demonstrate that DNA methylation GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death, time-to-coronary heart disease, time-to-cancer, its strong relationship with computed tomography data for fatty liver/excess visceral fat, and age-at-menopause. [2]

DNA methylation has also been suggested as a target in a regressive paradyme. If increased methylation is an indication of age, would a targeted therapy that reduces that methylation levels be an anti-aging intervention?

Laboratory Markers correlating with BASP

Multiple common laboratory markers included in studies like complete blood cell counts and blood chemistry panels also have demonstrated stistcically significant correlations with your BASP vs chronological ages. [3]

Multiple elements of facial recognition age determination. Skin is the largest human organ. Its visibility and accessibility make it a good BASP marker from facial images. There are several biomarkers associated with your eyes that also can contribute to an accurate estimate of your age. AI analysis of your face can produce an accurate indication of your BASP. [4]

[1] DNA Methylation Biomarkers in Aging and Age-Related Diseases

[2] DNA methylation GrimAge strongly predicts lifespan and healthspan

[3] 2021 Correlation analyses between age and indices in routine blood laboratory tests suggest potential aging biomarkers, Annals of Blood

[4]

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The primary addressable, interventional BASP targets are detailed in the following paragraph. It would represent the ultimate hubris to assume that this list in any way represents the final word, in both 1) an optimal list of targets, 2) most effective dosage; 3) most effective time of administration; 4) most effective interval of administration; 5) and/or the most effective interventional molecules. 

 On a personal note I can provide limited (N of 2) feedback on what is described at this point in time. Much like the mice in the Conboy study we have experienced improvements in energy, gastral intestinal function and comfort, memory, concentration and sleep.  Our mental outlook has dramatically improved and the feeling of heading toward a cliff that many older individuals experience has abated.  Total quality of life is at leat 50% better than prior to implementing this protocol. Activities of daily living have become much easier to accomplish. This work will continue for many years fine tuning the optimal age-regression protocol.  You own contribution to this information is critical. 

 If the word is bolded and underscored it is included in our inventory of supplemental interventions. 

1) Increasing levels of TGF-beta-1 are correlated with increasing age[4]. The Conboys in the referenced paper describe it as: “age-related elevation in the intensity of this pathway may contribute to diminished stem cell regeneration in the hippocampal niche, which combined with our prior results with the skeletal muscle stem cell niche would demonstrate conservation of signal transduction changes with age.”  ALK5 provides an effective and very druggable target that results in the downregulation or inhibition of TGF-beta-1 signaling.  Supplements able to inhibit ALK5 include EGEC, Fiesten, Qcertain, and Curcumin. Resveratrol [1] an Petrostilbene[] inhibit the signaling downstream from ALK5 at pSmad 2,3. 

 2) Levels of the hormone Oxytocin decline with age. 

 Oxytocin can be up-regulated by the administration of several forms of Oxytocin now available online.  

 Oxytocin can be up-regulated by multiple supplements including:

3) AKG is a required intermediary in the Krebs cycle. It also facilitates the assembly and transportation of many of the bodies building blocks; amino-acids. Multiple studies in multiple animal models have documented an increased life-span resulting from AKG supplementation.  

4) Glutathione is an important component of cellular metabolism and energy production. A recent paper described how the supplementation with N-acetylcysteine (NAC), and Glycine increased intercellular glutathione, producing dramatic and sustained improvements in multiple measurements, leading to an improved quality of life.  This included improved glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition. [2]  Another research group accomplished similar results providing only Lyophilized Glutathione as the interventional supplementation [3].  5) Leucine has demonstrated in multiple studies a longevity benefit [4]. Dehydroepiandrosterone (DHEA).  Vitamin D is expected to be a primary anti-aging medicine in the near future due to its numerous positive effects in the elderly population.

 5) Down regulation of IL-6. 

IL-6, perhaps considered one of the first aging biomarkers, was described as “a cytokine for gerontologists” (Ershler, 1993). IL-6 is the best characterized biomarker for “inflammaging,” a chronic low-grade inflammation that develops with advanced age and contributes to the pathogenesis of age-related diseases and most recently has been recognized as a core element of the secretome produced by senescent cells (Lopez-Otin et al., 2013; Ferrucci and Fabbri, 2018; Franceschi et al., 2018). High circulating levels of proinflammatory cytokines, such as IL-6 have been associated both cross-sectionally and prospectively with major age-related chronic diseases as well as with disability and frailty (Maggio et al., 2013). Insulin-like Growth Factor-1 (IGF-1 (IGF 1), which contributes to the decline of muscle strength with aging (Maggio et al., 2013; Johnson et al., 2020; Moaddel et al., 2021) 

 As the age increased by 1 year, IL-6 values increased by 0.05 pg/ml (95% CI: 0.02, 0.09; p < .01) [5]. 

REFERENCES:

[1] 2014 Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improvescardiac function via the TGF-!/Smad3 pathway

[2] 2021 Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial

[3] 2018 Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function

[4] 2011 Low-dose lithium uptake promotes longevity in humans and metazoans

[5] 2021 Defining IL-6 levels in healthy individuals: A meta-analysis