Spermidine and Spermine Are Enriched in Whole Blood of Nona/Centenarians

Abstract

Polyamines (putrescine, spermidine, and spermine) are a family of molecules that derive from ornithine through a decarboxylation process. They are essential for cell growth and proliferation, stabilization of negative charges of DNA, RNA transcription, translation, and apoptosis. Recently, it has been demonstrated that exogenously administered spermidine promotes longevity in yeasts, flies, worms, and human cultured immune cells. Here, using a cross-sectional observational study, we determined whole-blood polyamines levels from 78 sex-matched unrelated individuals divided into three age groups: Group 1 (31-56 years, n=26, mean age 44.6±6.07), group 2 (60-80 years, n=26, mean age 68.7±6.07), and group 3 (90-106 years, n=26, mean age 96.5±4.59). The total content of polyamines is significantly lower in groups 2 and 3 compared to group 1 (p=3.6×10(-12)). Interestingly, this reduction is mainly attributable to the lower putrescine content. Group 2 displays the lowest levels of spermidine and spermine. On the other hand, nona/centenarians (group 3) display a significantly higher median relative percentage content of spermine with respect to total polyamines, compared to the other groups (13.2% vs. 14.1% vs. 30.6%, p=6.0×10(-4)). For the first time, we report profiles of polyamines from the whole blood of healthy nona/centenarians, and our results confirm and extend previous findings on the role of polyamines in determining human longevity. However, although we found an important correlation between polyamines levels and age groups, further studies are warranted to fully understand the role of polyamines in determining life span. Also, longitudinal and nutritional studies might suggest potential therapeutic approaches to sustain healthy aging and to increase human life span.

Autophagy is a critical regulator of memory CD8+ T cell formation

“…We first confirmed that spermidine induces autophagy in T cells in vitro in a dose and time-dependent manner shown by increased levels of LC3-II (Figure 6D). Spermidine levels in the blood are known to decrease with age (Pucciarelli et al, 2012). To mimic this, we used the inhibitor of the natural spermidine synthesis pathway DFMO in the human Jurkat T cell line and found that autophagy levels detected by LC3 western blot significantly dropped in BafA treated samples and untreated samples (Figure 6E).…”

The Search for Antiaging Interventions: From Elixirs to Fasting Regimens

“…Endogenous spermidine concentrations decrease as the organism age, including in humans with the exception of centenarians (Pucciarelli et al, 2012). Acute injections of spermidine in mice activate autophagy in multiple organs (Morselli et al, 2011) while chronic spermidine feeding promotes increase in healthspan (Eisenberg et al, 2009).…”

Parkinson's disease as a result of aging

“…This protective effect has not been shown for other sirtuins (Dillin & Kelly, 2007) which, as occurs with the sirtuin 2, may even promote the cell death in animal models of PD (Outeiro et al ., 2007). Other agents that could be useful for modulating both aging and PD are the insulin growth factors (Mattson et al ., 2004; de Cabo et al ., 2014; Numao et al ., 2014), spermidine (Pucciarelli et al ., 2012; De La Hera et al ., 2013), metformin (Patil et al ., 2014), and rapamycin (Malagelada et al ., 2010; Liu et al ., 2013). …”