Higher IGF-1 and DHEA levels, longer telomere lengths

[Nelson Vergel]

Your life expectancy grows, the more anabolic – and fewer catabolic – hormones your body produces. Researchers at Harvard Medical School reached this conclusion after performing a molecular-epidemiological study on 925 men and women over the age of 54.


The more anabolic hormones your body produces, the longer you live

 

[Cataceous]

How do we reconcile this with the link between higher IGF-1 and increasing mortality?

 

[Nelson Vergel]

Damn, I knew someone was going to ask that! LOL

This small study was to measure telomere length. That is only one of the factors involved in longevity.

I challenge anyone on here to help me digest this for others:

ROLE of IGF-1 System in the Modulation of Longevity: Controversies and New Insights From a Centenarians' Perspective

 

[Sean Mosher]

Challenge indeed.
Their basic conclusion was still that they still remain unclear which IGF-1 levels/ranges increase longevity.

I clearly understood the part below tho ;-)

Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 

[littlemanb]

Growth hormone supplementation would probably be an excellent start after 55 years..

 

[tareload]

Your life expectancy grows, the more anabolic – and fewer catabolic – hormones your body produces. Researchers at Harvard Medical School reached this conclusion after performing a molecular-epidemiological study on 925 men and women over the age of 54.


The more anabolic hormones your body produces, the longer you live

One way to "improve" the apparent "statistical significance" when testing models especially logistic (linear) models is to include in the fitting set extra variables, which are correlated, to increase the degrees of freedom in your model and change the residual variance.

for more info: What is the effect of having correlated predictors in a multiple regression model?
However, this is typically frowned upon. I don't have access to their models but the authors don't share in the paper if there was a high correlation between IL-6 and cortisol which has been shown in the literature (see for example):

Relationships between inflammatory cytokine and cortisol responses in firefighters exposed to simulated wildfire suppression work and sleep restriction

If the cortisol score was removed from the A/C imbalance summary, I'm wondering in the odd's ratio for the A/C imbalance summary would still be significant. The odds ratio with 95% CI ain't very strong. Seems like the author's are just picking up the IL-6 effect which makes sense, long-term inflammation bad.

Abstract
The interplay between inflammatory and cortisol responses modulates an appropriate response to a stressor. Exposure to severe stressors, however, may alter the actions and relationships of these responses and contribute to negative health outcomes. Physical work and sleep restriction are two stressors faced by wildland firefighters, yet their influence on the relationship between inflammatory and cortisol responses is unknown. The aim of the present study was to quantify the relationship between the cytokine and cortisol responses to sleep restriction while performing simulated physical wildfire suppression work. Firefighters completed 3 days of simulated physical firefighting work separated by either an 8-h (Control condition; n = 18) or 4-h sleep (Sleep restriction condition; n = 17) opportunity on each of the two nights. Salivary cortisol and inflammatory cytokines (IL-6, IL-8, IL-1β, TNF-α, IL-4, and IL-10) were measured throughout each day. An increase in morning IL-6 was related to a rise (6.2%, P = 0.043) in evening cortisol among firefighters in the sleep restriction condition. Higher morning IL-6 levels were related to increased (5.3%, P = 0.048) daily cortisol levels, but this relationship was not different between conditions. Less pronounced relationships were demonstrated between TNF-α, IL-10, IL-4, and cortisol independent of the sleep opportunity, but relationships did not persist after adjusting for demographic factors and other cytokines. These findings quantify the relationship between cytokine and cortisol responses among wildland firefighters exposed to simulated occupational stressors. Potential disturbances to the IL-6 and cortisol relationship among sleep-restricted firefighters’ supports further investigations into the negative health effects related to possible imbalances between these systems.
Keywords: Cortisol, cytokines, firefighters, physical work, sleep restriction

 

[tareload]

How do we reconcile this with the link between higher IGF-1 and increasing mortality?

These two papers, given the data available to us, don't appear inconsistent. Mid range IGF-1 ("normal") + low level of inflammation (typically shows up as significant level of IL-6) is recipe for success.

Note the A/C imbalance score isn't a ratio, the authors just added up the number of tests that ranged outside the cutoffs:

A/C imbalance was considered using three parameterizations. First, individual associations of at-risk levels of each anabolic and catabolic hormone to telomere length were investigated. Second, we also considered the balance between anabolic and catabolic hormones by examining DHEAS/cortisol and IGF-1/cortisol ratios (as often used in the literature, e.g., Cruess et al., 1999; Daly, Rich, Kelin, 1998). Third, a summary measure of A/C imbalance was created for each respondent by summing the number of at-risk anabolic and catabolic markers (range 0–6; individuals with high or low cortisol levels received one point for the score). Logistic regression models were used to determine the relationship between at-risk levels of individual anabolic and catabolic hormones, DHEAS/cortisol and IGF-1/cortisol ratios, and the summary measure of A/C imbalance with short telomere length. All models were adjusted for age, sex, marital status, and urban/rural residency using STATA Version 11 (StataCorp, 2007).

This method is juiced probably because cortisol and IL-6 are correlated in this population. Therefore, I don't agree with Ergo-Log title : "The more anabolic hormones your body produces, the longer you live". Their subtitle should be normal anabolic hormones and low inflammation (correlated with cortisol), the longer you live. The authors "A/C imbalance summary" score is not indicative of an imbalance between anabolic and catabolic hormones, it's indicative of abnormal level of IL-6 that's probably correlated with cortisol. Hope this makes sense.

 

[Nelson Vergel]

A new study:

Cross‐sectional associations of sex hormones with leucocyte telomere length, a marker of biological age, in a community‐based cohort of older men

https://onlinelibrary.wiley.com/doi/abs/10.1111/cen.13918

Context
Telomeres protect chromosomes from damage, and shorter leukocyte telomere length (LTL) is a marker of advancing biological age. The association between testosterone (T) and its bioactive metabolites, dihydrotestosterone (DHT) and oestradiol (E2) with telomere length, particularly in older men, is uncertain. The study aimed to clarify associations of sex hormones with LTL in older men.

Participants and methods
We used cross‐sectional data from 2913 men aged 76.7 ± 3.2 years with morning blood samples assayed for T, DHT, E2 (mass spectrometry), and sex hormone‐binding globulin (SHBG, immunoassay), to correlate sex hormones with LTL measured using PCR and expressed as T/S ratio in multivariable linear regression models adjusted for age, cardiometabolic risk factors and cardiovascular disease history.

Results
Average difference per decade of age was T −0.46 nmol/L, DHT −0.11 nmol/L, E2 −7.5 pmol/L, SHBG +10.2 nmol/L and LTL (T/S ratio) −0.065. E2 correlated with T/S ratio (r = 0.038, P = 0.039) and SHBG was inversely correlated (r = −0.053, P = 0.004). After multivariable adjustment, E2 was associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, P = 0.043), T and DHT were not associated. When E2 and SHBG were simultaneously included, E2 remained positively (coefficient 0.014, P = 0.014) and SHBG inversely (coefficient −0.013, P = 0.037) associated with T/S ratio.

Conclusions
In older men, neither T nor DHT is associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated, thus relating sex hormone exposure to lower biological age. Further research is needed to determine causality and clarify the role of sex hormones in male ageing.

 

[JPB]

As heteroplasmic rates increase with age, the general consensus is that adding growth factors to the mix increases cancer risk. This poses a conundrum to aging muscle heads. Metformin is a good example of this conundrum. Lower your cancer risk but lose your gainz. Bummer.