Humans evolved unique
gene variants that protect older adults from neurodegenerative disease, thus
preserving their valuable contributions and delaying dependency
Newswise, December 1, 2015 — Many human gene variants have
evolved specifically to protect older adults against neurodegenerative and
cardiovascular diseases, thus preserving their contributions to society, report
University of California, San Diego School of Medicine researchers in the
November 30 issue of Proceedings of the National Academy of Sciences.
“We unexpectedly discovered that humans have evolved gene
variants that can help protect the elderly from dementia,” said Ajit Varki, MD,
Distinguished Professor of Medicine and Cellular and Molecular Medicine at UC
San Diego School of Medicine, adjunct professor at the Salk Institute for
Biological Studies and co-director of the UC San Diego/Salk Center for Academic
Research and Training in Anthropogeny (CARTA).
“Such genes likely evolved to preserve valuable and wise
grandmothers and other elders, as well as to delay or prevent the emergence of
dependent individuals who could divert resources and effort away from the care
of the young.” Varki led the study, along with Pascal Gagneux, PhD, associate
professor of pathology and associate director of CARTA.
The standard model of natural selection predicts that once the
age of reproduction ends, individuals die.
That’s because selection early in life strongly favors
variants that benefit reproductive success, even at the cost of negative
consequences late in life — one major reason we age. This is indeed the case in
almost all vertebrates.
Humans (and certain whales) are an exception to this rule,
living decades beyond reproductive age. Such elders contribute to the fitness
of younger individuals by caring for grandchildren and also by passing down
important cultural knowledge.
Age-related cognitive decline compromises these benefits, and
eventually burdens the group with the need to care for dependent older members.
In this first-of-its kind discovery, Varki, Gagneux and their
teams initially focused on the gene that encodes the CD33 protein. CD33 is a
receptor that projects from the surface of immune cells, where it keeps immune
reactions in check, preventing “self” attack and curtailing unwanted
inflammation.
Previous studies suggested that a certain form of CD33
suppresses amyloid beta peptide accumulation in the brain. Amyloid beta
accumulation is thought to contribute to late-onset Alzheimer’s disease, a
post-reproductive condition that uniquely affects humans and is aggravated by
inflammation and cerebral vascular disease.
The researchers compared CD33 regulation in humans and our
closest living relatives, chimpanzees. They found that levels of the CD33
variant that protects against Alzheimer’s are four-fold higher in humans than
chimpanzees.
They also found human-specific variations in many other genes
involved in the prevention of cognitive decline, such as APOE. The ancestral
form of the gene, APOE4, is a notorious risk factor for Alzheimer’s and
cerebral vascular disease. But this study finds that variants APOE2 and APOE3
seem to have evolved to protect from dementia. All of these protective gene
variants are present in Africa, and thus predate the origin of our species.
This finding is in keeping with the valuable role of the elderly across human
societies.
“When elderly people succumb to dementia, the community not
only loses important sources of wisdom, accumulated knowledge and culture, but
elders with even mild cognitive decline who have influential positions can harm
their social groups by making flawed decisions,” Gagneux said.
“Our study does not directly prove that these factors were
involved in the selection of protective variants of CD33, APOE and other genes,
but it is reasonable to speculate about the possibility.
“After all, inter-generational care of the young and
information transfer is an important factor for the survival of younger kin in
the group and across wider social networks or tribes.”
Additional study co-authors include Flavio Schwarz, Stevan A.
Springer, Tasha Altheide, Nissi M. Varki, all of UC San Diego.
This research was funded, in part, by the National Institutes
of Health (grants P01HL107150 and R01GM095882) and the Harold and Leila Mathers
Foundation.
Full study: http://www.doi.org/10.1073/pnas.1517951112
