LONGEVITY: Genetic studies published in May 1998

Kathryn Aegis (aegis@igc.apc.org)
Fri, 8 May 1998 20:07:33 +0000

The May issue of the American Journal of Human Genetics contains two
articles that pertain to aging at the cellular level. One reviews
genetic strategies to study it, and the other offers more support for
the theory that programmed cell senescence results in the
manifestations of aging.


'Causes, Effects and Constraints in the Genetics of Human
Longevity', by Francois Schachter of the Laboratory of Human
Immunogenetics, Pasteur Institute, Paris (page 1008)

Schachter uses a five-level biological heirarchy (Finch and Rose,
1995) to examine various genetic factors in human aging. Schachter
opens by noting that Jeanne Calment (oldest known humanand recently
deceased at the age of 123) was descended from agenetic lineage that
contained a disproportionate number of familymembers who lived beyond
the age of 80. Due to the aggregatenature of the longevity trait,
however, he sees little utility in pursuing strategies that would
increase the occurrence of this trait. Nor has the recent increase
in the mean human MLS (maximum life span) resulted in an increase of
the actual MLS, which has continued to hover at ~120. In the next
few sections of thearticle, Schachter makes the case for rejection of
attempting to regulate or propogate longevity as a trait: 'The four
genes so far implicated in longevity, APOE, ACE, HLA-DR, and PAI-1,
share common features: (1) they have an impact on intermediary
traits, such as plasma levels of a homeostatic protein or immune
response, and (2) they display gene-environment interactions in
normal adult populations. . . these genes appear to affect longevity
by modulating an individual's responses to life-threatening
disorders, not by regulating MLS as an intrinsic physiological

After a section on CA (compensatory adaptation) and on chronobiology,
Schachter moves on to the human genome and our murky understanding of
its role in longevity. He suggests the potential utility o f
X-chromosomal loci as a testing ground for models of DNA damage in
cellular aging: 'the X chromosome is at the same time protected in
the germ line and critically vulnerable in the soma. . .' He cites a
study that indicates a significant drop in the lifespan of daughters
born of elderly fathers compared to sons born of the same fathers.


'The Genetics of Cullular Senescence' by Nathalie G. Berube, James R.
Smith, and Olivia M. Pereira-Smith of the Huffington Center on Aging, Baylor College of Medicine, Houston (page 1015).

The authors conclude that identification of the genes involved in
regulating programmatic replicative cell senescence could lead to
greater understanding of the aging process and strategies to manage
Comments from John Ashkenas, editor: 'Do our bodies age as
iron rusts-passively, with the accumulation of damage due to
external insults? Or, are the physiological changes of aging better
conceived as an intrinsic development process, similar to those of
our early histories? Berube, et al, review the recent evidence from
cell-culture studies in favor of the latter model. As Berube et al.
demonstrate, cells must continue to express several mortality
factors if they are to retain their normal capacity to senescence,
that is, to stop proliferating after a characteristic number of
divisions . The accumulation of sensescent cells in various tissues
may explain many of the conspicuous features of aging.'

These articles can be accessed online in full text at