Exercise, APOE genotype, and the evolution of the human lifespan

Raichlen, David A.; Alexander, Gene E.

doi:10.1016/j.tins.2014.03.001

Cited by 106 publications

(115 citation statements)

References 123 publications

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“…An increased total mortality for ApoE ε4 carriers has been reported in several studies [35,36]. Thus, one might argue that the excess dementia-related mortality among the ε4 carriers in our study is merely due to increased total mortality (our cases were dead, while controls were alive).…”

Section: Discussionsupporting

confidence: 51%

Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR)

Strand

Rosness²,

Engedal³

et al. 2015

Dement Geriatr Cogn Disord

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Background/Aims: Our aims were two-fold: firstly, to investigate the association and interaction between apolipoprotein E (ApoE), lifestyle risk factors and dementia-related mortality and, secondly, to examine if using dementia-related mortality yielded comparable risk estimates for the ApoE genotypes as reported in studies using a clinical dementia diagnosis as the end point. Methods: We used a nested case-control study with 561 cases drawn from dementia deaths in the Cohort of Norway (CONOR) and 584 alive controls. Results: ApoE ε4 carriers were at increased risk of dementia-related mortality compared to noncarriers [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.93-3.13], and ε4 homozygotes were at particularly high risk (OR 7.86, 95% CI 3.80-13.8), while the ε2 type was associated with a lower risk. The highest risk of dementia-related mortality was found among ε4 carriers with more lifestyle risk factors (ε4 carriers who were smokers, hypertensive, physically inactive and diabetics) versus ε4 noncarriers without lifestyle risk factors (OR 15.4, 95% CI 4.37-52.4). The increased risk was additive, not multiplicative. Conclusions: Ensuring a healthy lifestyle is important to be able to prevent dementia in populations at large, but especially for ε4 carriers. Using dementia mortality gives comparable results for the ApoE-dementia association as studies using clinical dementia diagnoses.

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Section: Discussionsupporting

confidence: 51%

Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR)

Strand

Rosness²,

Engedal³

et al. 2015

Dement Geriatr Cogn Disord

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“…Such reductions in capacity in the context of neurologically healthy aging are expressed as age-related brain atrophy. This concept also suggests that genetic risk factors for neurodegenerative diseases, such as Alzheimer’s disease, that were maintained throughout our evolutionary history (e.g., the Apolipoprotein E [APOE] ε4 allele [56]) may only lead to enhanced risk of cognitive impairment or vulnerability to dementia when met with a lack of exercise-induced stimulation (Figure 1). …”

Section: The Adaptive Capacity Modelmentioning

confidence: 99%

Adaptive Capacity: An Evolutionary Neuroscience Model Linking Exercise, Cognition, and Brain Health

Raichlen

Alexander

2017

Trends in Neurosciences

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The field of cognitive neuroscience was transformed by the discovery that exercise induces neurogenesis in the adult brain, with the potential to improve brain health and stave off the effects of neurodegenerative disease. However, the basic mechanisms underlying exercise-brain connections are not well understood. Here, we use an evolutionary-neuroscience approach to develop the Adaptive Capacity Model (ACM), detailing how and why physical activity improves brain function based on an energy-minimizing strategy. Building on studies showing a combined benefit of exercise and cognitive challenge to enhance neuroplasticity, our ACM addresses two fundamental questions: 1) what are the proximate and ultimate mechanisms underlying age-related brain atrophy? and 2) how do lifestyle changes influence the trajectory of healthy and pathological aging?

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“…We noted that the evolutionary history of CD33 is similar to that of APOE, in that both genes have derived alleles that protect from a novel liability that is uniquely human (31)(32)(33). The APOE gene, which encodes for the plasma protein APOE, is polymorphic in humans.…”

Section: Cd33m Is Expressed At Higher Levels In Humans Than In Chimpamentioning

confidence: 99%

Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline

Schwarz

Springer

Altheide

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer’s dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer’s disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin.

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Exercise, APOE genotype, and the evolution of the human lifespan

Cited by 106 publications

References 123 publications

Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR)

Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR)

Adaptive Capacity: An Evolutionary Neuroscience Model Linking Exercise, Cognition, and Brain Health

Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline

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