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The SENS PlatformThe "Seven Deadly Things" and Why There Are Only Seven

SENS is a practical, foreseeable approach to curing aging because all the types of metabolic side-effects whose accumulation is (or is even hypothesised to be) eventually pathogenic are amenable to repair (or in some cases obviation, i.e. disruption of the mechanism by which they become pathogenic) by techniques that, according to the experimentalists who have performed the key work on which those techniques build, can (with adequate funding) probably be implemented in mice within a decade or so. There are seven major categories of such damage, listed below, along with the leading technique or techniques that can address them. Follow the links to read more detail about these techniques. I apologise that these more detailed pages do not yet include references to the literature. In most cases you can find the key references in my relevant publications, which are all available here.

Note: The dates given are when the category of damage in question was first proposed, in the gerontology literature, to be responsible for aging or some major age-related cause of death or debilitation. The earlier ones may not in fact be the first such mention, but they are well-known and often cited as pioneering publications in the area in question. The full citations are below the table. The relevance of these dates is that they are all over 20 years ago. The fact that we have not discovered another major category of even potentially pathogenic damage accumulating with age in two decades, despite so tremendous an improvement in our analytical techniques over that period, strongly suggests that no more are to be found -- at least, none that would kill us in a presently normal lifetime.

Damage rising with age	Date [ref below]	Reversible or obviatable by [see links for more info]
Cell loss, cell atrophy	1955	Stem cells, growth factors, exercise
Nuclear [epi]mutations (only cancer matters)	1959/1982	WILT (Whole-body Interdiction of Lengthening of Telomeres)
Mutant mitochondria	1972	Allotopic expression of 13 proteins
Death-resistant cells	1965	Cell ablation, reprogramming
Extracellular crosslinks	1981	AGE-breaking molecules/enzymes
Extracellular junk	1907	Phagocytosis; beta-breakers
Intracellular junk	1959	Transgenic microbial hydrolases

The above table is to some extent similar to Table 4.3 in Holliday's 1995 book Understanding Ageing, though with important differences resulting from the focus on types of damage rather than types of maintenance. Some of the studies cited here were in fact incorrect in their interpretation of the data they examined, but the point is that they brought the corresponding type of damage to the fore as a candidate component of aging.

• Alzheimer A. Über eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift für Psychiatrie und psychisch-gerichtliche Medizin, Berlin, 1907, 64: 146-148.
• Brody H. Organization of the cerebral cortex III. J Comp Neurol 1955; 102:511-556.Szilard L. On the nature of the ageing process. Proc Natl Acad Sci USA 1959; 45:35-45.
• Strehler BL, Mark DD, Mildvan AS, Gee MV. Rate and magnitude of age pigment accumulation in the human myocardium. J Gerontol 1959; 14:430-439.
• Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37:614-636.
• Harman D. The biologic clock: the mitochondria? J Am Geriatr Soc 1972;20:145-147.
  Monnier VM, Cerami A. Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science 1981;211:491-493.
• Cutler RG. The dysdifferentiation hypothesis of mammalian aging and longevity. In: The Aging Brain: Cellular and Molecular Mechanisms of Aging in the Nervous System (Gicobini E et al., eds), Raven (New York), 1982, pp. 1-19.

 

Active SENS Research Strands

New discoveries in the realm of biological science reveal common mechanisms are shared by age-related diseases and conditions. More significantly, research suggests that these mechanisms can be modified. These new discoveries indicate that more benefit could be realized by treating age-related diseases not as distinct disorders, but rather as a collection of syndromes tied together by a few common threads. We believe the time has come to declare the arrival of the real "war on aging" and use our new tools to attack aging at its root, the fundamental biological processes which drive it.

The Methuselah Foundation is working to develop science that is capable of repairing the damage that accumulates over time to cause the pathology of age-related disease and dysfunction. Foundation initiatives join those of many research teams already hard at work towards repairing certain forms of this damage. Research into stem cells promises to help rebuild tissues and address the problem of cell loss with age, for example.

However, some forms of damage are not currently under strong investigation, and it is on therapies for these less scrutinized forms that the Methuselah Foundation concentrates it efforts, so as to ensure that all age-related damage be examined with an eye to developing therapies of repair and prevention.

To this end the Foundation currently funds two projects:

1) LysoSENS - isolation and targeting of bacterial enzymes to the lysosome to degrade otherwise indigestible and damaging 'junk'.

2) MitoSENS - the transfer of damage prone mitochondrial genes from vulnerable mitochondria to the relative safety of the cellular nucleus

With preliminary results from LysoSENS proving exciting we are eager to push forward and add even more research projects aimed at removing the damage of aging to our list. If you wish to support this research you may do so by joining the ranks of generous donors who see to make this new aging science a reality. Click here to donate.