XClose

UCL Great Ormond Street Institute of Child Health

Home

Great Ormond Street Institute of Child Health

Menu

Vampires and Supercentenarians: Why do some people live extreme long lives?

Supervisors: Professor Kevin Mills, Dr Simon Eaton and Dr Wendy Heywood

Background: 

Why some human beings live longer than others has fascinated mankind for 1000s of years, with legends of vampires using the blood of the young to perpetuate long life.  However, recent evidence has demonstrated that parabiosis of giving plasma from young animals injected into older animals, can actually induce antiaging effects and improve memory (1,2).  We participated recently in a large European H2020 consortium looking at the metabolism of supercentenarians (people who live >105 years of age).  Contrary to the belief that Supercentenarians had a perfect metabolism, we demonstrated that these small groups of people actually have a partial deficiency in enzymes involved in energy metabolism.  This deficiency actually forcing their energy metabolism towards the ketogenesis or the equivalent of ketogenic diet.  It is well known that ketogenesis is neuroprotective and results in significantly less free radical production than glycolysis and gluconeogenesis.   Therefore, we would like to investigate the phenomenon of changing energy metabolism and the effect it has on the cell by using hepatocyte and neuronal cell models, combined with state of the art omic technologies of proteomics, metabolomics/fluxomics and lipidomics. 

In addition, we will study the parabiosis effect gained from the plasma transplants from young and older individuals on the regeneration and anti-aging process in order to identify those molecules critical for this process (3). The final translational outcome of this research is to identify the mechanisms, and factors or dietary interventions that could potentially increase longevity or reduce neurodegeneration as observed in Alzheimer’s Disease and other dementias.

Aims/Objectives:

a)  Develop a ‘normal’ homoeostatic profile and a ‘supercentenarian’ model of a cell.

b)  Develop stable isotope tracer assays to monitor critical biochemical pathways involved in aging and neurodegeneration

c)  Elucidate the effects of manipulating the energy pathways of a cell to determine the beneficial effects of the ketogenic diet

d)  Find the ‘x-factor’ parabiosis ingredient in young people’s plasma that advocates anti-aging and neuroprotection.

Methods:

Stable isotopes of amino acids, metabolites and lipids will be fed to cell models under different metabolic conditions (high glucose/low lipid vs. low glucose vs high lipid). These stable isotope tagged molecules will be the perfect tracer in that they behave identically and cannot be distinguished by the cell from endogenous molecules. Thus, they are metabolised exactly the same.  Identifying a tagged protein, metabolite or lipid can only be achieved by ‘weighing’ the molecules using high-resolution mass spectrometers. By feeding cellular models these stable isotope precursors of amino acids, metabolites, drugs and lipids, we can detect the presence of these ‘tracer tags’ as they are metabolised (Figure 1). We will use a cocktail of stable isotope tracer molecules that will allow us to study all metabolic pathways thought to be critical in the aging and neurodegenerative process.  

References:

  1. Plasma from Young Rats Injected into Old Rats Induce Antiaging Effects, Rejuvenation Res, 2021 Jun;24(3):206-212. Tripathi et al (2021)
  2. Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17 , Nature volume 605: 509–515. Iram et al (2022)
  3. Vampires 2.0? The ethical quandaries of young blood infusion in the quest for eternal life. Med Health Care Philos 2020 Sep;23(3):421-432. Lavazza et al (2020)