Theory 7 of WHY WE AGE. Thymus failure

As we age, our immune systems grow progressively weaker, with diminished ability to produce B and T cells or respond to antigens sensitively.  Vaccines for older adults often have higher doses of antigen.

The Thymus gland is vital to our immune system. T-cells originate in the Thymus.  Deterioration of that gland is a major cause of aging.  The Principal Investigator, Gregory M Fahy, PhD, and his group conducted the TRIIM (Thymus Regeneration, Immunorestoration, and Insulin Mitigation) study on 9 older white males. T caution their clinical study was small and lacked a control group.  They are optimistic that a person’s biological age can be reversed. Their findings were published in 2019 in Aging Cell .

“To date, evidence that systemic aging can be reversed has not been substantiated by determinations of epigenetic age, which can now provide a simple but compelling indication of biological as opposed to chronological age (Horvath & Raj, 2018; Jylhava, Pedersen, & Hagg, 2017). In addition, there is a need to specifically address immunosenescence stemming from thymic involution (Bodey, Bodey, Siegel, & Kaiser, 1997). Thymic involution leads to the depletion of critical immune cell populations (Arnold, Wolf, Brunner, Herndler-Brandstetter, & Grubeck-Loebenstein, 2011), resulting in a collapse of the T-cell receptor (TCR) repertoire in humans after the age of ~63 (Naylor et al., 2005), and is linked to age-related increases in cancer incidence (Falci et al., 2013), infectious disease (Ventevogel & Sempowski, 2013), autoimmune conditions (Goronzy & Weyand, 2003), generalized inflammation (Goronzy & Weyand, 2003), atherosclerosis (Dai, Zhang, Wang, Wu, & Liang, 2018), and all-cause mortality (Fernando-Martinez et al., 2013; Roberts-Thomson, Whittingham, Youngschaiyud, & Mackay, 1974; Strindhall et al., 2007). In contrast, maintained immune function is seen in centenarians (Strindhall et al., 2007).”

“For these reasons, we conducted what may be the first human clinical trial designed to reverse aspects of human aging, the TRIIM trial, in 2015–2017. “

“we combined recombinant human growth hormone with both dehydroepiandrosterone (DHEA) and metformin in an attempt to limit the “diabetogenic” effect of GH (Fahy, 2003, 2010; Weiss, Villareal, Fontana, Han, & Holloszy, 2011). DHEA has many effects, in both men and women, that oppose deleterious effects of normal aging (Cappola et al., 2009; Forti et al., 2012; Shufelt et al., 2010; Weiss et al., 2011). Metformin is a powerful calorie restriction mimetic in aging mice (Dhahbi, Mote, Fahy, & Spindler, 2005) and has been proposed as a candidate for slowing aging in humans (Barzilai, Crandall, Kritchevsky, & Espeland, 2016). Neither DHEA (Riley, Fitzmaurice, & Regelson, 1990) nor metformin are known to have any thymotrophic effects of their own.”

DOSAGE given for one year included a personally prescribed dosage of human growth hormone and DHEA and metformin.  Note that DHEA and metformin alone did not work.