Bio-thermodynamics and aging

I suspect nature is constrained by basic physics/chemistry/thermodynamics in a variety of interesting ways.

For example, chemical reactions (and thus biological processes) proceed more quickly when they are warm than cold–this is pretty much a tautology, since temperature=movement–and thus it seems reasonable to expect certain biological processes to proceed more slowly in colder places/seasons than in warmer ones.

The Greenland Shark, which lives in very cold waters, lives to be about 300-500 years old. It’s no coincidence:

Temperature is a basic and essential property of any physical system, including living systems. Even modest variations in temperature can have profound effects on organisms, and it has long been thought that as metabolism increases at higher temperatures so should rates of ageing. Here, we review the literature on how temperature affects longevity, ageing and life history traits. From poikilotherms to homeotherms, there is a clear trend for lower temperature being associated with longer lifespans both in wild populations and in laboratory conditions. Many life-extending manipulations in rodents, such as caloric restriction, also decrease core body temperature.

This implies, in turn, that people (or animals) who overeat will tend to die younger, not necessarily due to any particular effects of having extra lumps of fat around, but because they burn hotter and thus faster.

Weighing more may trigger certain physiological changes–like menarchy–to begin earlier due to the beneficial presence of fat–you don’t want to menstruate if you don’t have at least a little weight to spare–which may in turn speed up certain other parts of aging, but there could be an additional effect on aging just from the presence of more cells in the body, each requiring additional metabolic processes to maintain.

Increased human height (due to better nutrition) over the past century could have a similar effect–shorter men do seem to live longer than taller men, eg: 

Observational study of 8,003 American men of Japanese ancestry from the Honolulu Heart Program/Honolulu-Asia Aging Study (HHP/HAAS), a genetically and culturally homogeneous cohort followed for over 40 years. …

A positive association was found between baseline height and all-cause mortality (RR = 1.007; 95% CI 1.003–1.011; P = 0.002) over the follow-up period. Adjustments for possible confounding variables reduced this association only slightly (RR = 1.006; 95% CI 1.002–1.010; P = 0.007). In addition, height was positively associated with all cancer mortality and mortality from cancer unrelated to smoking. A Cox regression model with time-dependent covariates showed that relative risk for baseline height on mortality increased as the population aged. Comparison of genotypes of a longevity-associated single nucleotide polymorphism in FOXO3 showed that the longevity allele was inversely associated with height. This finding was consistent with prior findings in model organisms of aging. Height was also positively associated with fasting blood insulin level, a risk factor for mortality. Regression analysis of fasting insulin level (mIU/L) on height (cm) adjusting for the age both data were collected yielded a regression coefficient of 0.26 (95% CI 0.10–0.42; P = 0.001).

The more of you there is, the more of you there is to age.

Interesting: lots of data on human height.

But there’s another possibility involving internal temperature–since internal body temperature requires calories to maintain, people who “run hot” (that is, are naturally warmer) may burn more calories and tend to be thinner than people who tend to run cool, who may burn fewer calories and thus tend to weigh more. Eg, low body temperature linked to obesity in new study: 

A new study has found that obese people (BMI >30) have lower body temperature during the day than normal weight people. The obese people had an average body temperature that was .63 degrees F cooler than normal weight people. The researchers calculated that this lower body temperature—which reflects a lower metabolic rate—would result in a body fat accumulation of approximately 160 grams per month, or four to five pounds a year, enough for the creeping weight gain many people experience.

There’s an interesting discussion in the link on thyroid issues that cause people to run cold and thus gain weight, and how some people lose weight with thyroid treatment.

On the other hand, this study found the opposite, and maybe the whole thing just washes out to women and men having different internal temperatures?

Obese people are–according to one study–more likely to suffer mood or mental disorders, which could also be triggered by an underlying health problem. They also suffer faster functional decline in old age:

Women had a higher prevalence of reported functional decline than men at the upper range of BMI categories (31.4% vs 14.3% for BMI > or =40). Women (odds ratio (OR) = 2.61, 95% confidence interval (CI) = 1.39-4.95) and men (OR = 3.32, 95% CI = 1.29-8.46) exhibited increased risk for any functional decline at BMI of 35 or greater. Weight loss of 10 pounds and weight gain of 20 pounds were also risk factors for any functional decline.

Note that gaining weight and losing weight were also related to decline, probably due to health problems that caused the weight fluctuations in the first place.

Of course, general physical decline and mental decline go hand-in-hand. Whether obesity causes declining health, declining health causes obesity, or some underlying third factor, like biological aging underlies both, I don’t know.

Anyway, I know this thought is a bit disjointed; it’s mostly just food for thought.

African Americans, Hispanics, and longevity

I’ve known for a while that women live longer than men, Hispanic Americans live longer than Euro Americans, and the oldest people in the US are disproportionately black:

Susannah Mushatt Jones, 116 years old, is not only the oldest woman in the US, but also the entire world.
At 116 years old, Susannah Mushatt Jones is not only the oldest woman in the US, but also the entire world.

One theory I considered was that higher infant mortality rates in Mexico (I don’t actually know the infant mortality rates in Mexico, this is just an idea,) results in the deaths of premature infants and others with severe health problems, whereas in the US these infants survive for several years–maybe even decades–before dying. The population of Hispanic immigrants, therefore, does not include these children–they’re already gone–but the US population does. This could result in a higher life expectancy among the immigrants than among non-immigrants.

But what about women and blacks? Their infant mortality would be included in the native rates, and even if worse medical care resulted in higher infant mortality among them, this still wouldn’t explain why so many supercentenarians are black.

While researching hippocampi yesterday, I ran across an article about hippocampal volumes in the elderly: Brain Morphology in Older African Americans, Caribbean Hispanics, and Whites From Northern Manhattan

We already know that different people age at different rates, but it appears as well that different races age at different rates, with black brains aging the slowest:

Results of the regression analysis revealed significant effects of age, sex, vascular disease history, and race/ethnicity on relative brain volume (F5,685 = 38.290, P < .001). For each additional year in age, there was an associated 0.3% decrease in relative brain volume (β = −0.003, t = 10.34, P < .001) (Figure 2). Relative brain volume among women was 2% larger than that among men (β = 0.02, t = 5.93, P < .001). Hispanic (β = 0.03, t = 7.20, P < .001) and African American (β = 0.02, t = 4.09, P < .001) participants had 2.8% and 1.6% larger relative brain volumes than white subjects, respectively. Finally, for each additional vascular disease, there was a 0.5% associated reduction in relative brain volume (β = −0.005, t = −2.70, P < .001). When interaction terms were entered into the model, none were significant, demonstrating that the association of vascular disease history and age with relative brain volume did not differ across race/ethnicity or sex. Analysis of variance controlling for age and vascular disease history confirmed main effects of sex (F1,685 = 34.906, P < .001) and race/ethnicity (F2,685 = 23.528, P < .001) but no sex × race/ethnicity interaction (F2,685 = 0.167, P =.85) (Figure 3).

Relative brain volume across racial/ethnic groups and by sex.
Relative brain volume across racial/ethnic groups and by sex.
relationship among chronologic age, race/ethnicity, and relative brain volume.
relationship among chronologic age, race/ethnicity, and relative brain volume.


So why are white males (at least in these samples) aging so quickly?

The Insidious Approach of Death

A friend recently attended their 20th highschool reunion, the sort of event that makes one feel very old. Worse, three of their classmates have already died.

I thought that sounded way statistically unlikely, especially given the group’s demographics, but I ran the numbers, and it turns out that it’s only a little unlikely. Given the small N, we’re probably talking about random chance making the class unlucky rather than a particular propensity for death, but it’s unfortunate either way.

Highschool reunions are also a great (by which I mean depressing) opportunity to see who has aged the most. Some classmates look hardly older than the last time you saw them, while others look like they got hit by a semi full of old. Hopefully not you, of course.

In “Quantification of biological aging in young adults,” Belsky et al confirm what I’ve long suspected: that different people age at radically different rates, not just emotionally/mentally, but also biologically.

From the abstract: “We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older.” (bold mine.)

” We scaled the Pace of Aging so that the central tendency in the cohort indicates 1 y of physiological change for every one chronological year. On this scale, cohort members ranged in their Pace of Aging from near 0 y of physiological change per chronological year to nearly 3 y of physiological change per chronological year.”

“Study members with advanced Biological Age performed less well on objective tests of
physical functioning at age 38 than biologically younger peers (Fig. 5). They had more difficulty with balance and motor tests (for unipedal stance test of balance, r = −0.22, P < 0.001; for grooved pegboard test of fine motor coordination, r = −0.13, P < 0.001), and they were not as strong (grip strength test, r = −0.19, P < 0.001).”

“Study members with older Biological Ages had poorer cognitive functioning at midlife (r = −0.17, P < 0.001). Moreover, this difference in cognitive functioning reflected actual cognitive decline over the
years. When we compared age-38 IQ test scores to baseline test scores from childhood, study members with older Biological Age showed a decline in cognitive performance net of their baseline
level (r = −0.09, P = 0.010).”

“Neurologists have also begun to use high-resolution 2D photographs of the retina to evaluate age-related loss of integrity of blood vessels within the brain. Retinal and cerebral small vessels
share embryological origin and physiological features, making retinal vasculature a noninvasive indicator of the state of the brain’s microvasculature (32). Retinal microvascular abnormalities are associated with age-related brain pathology, including stroke and dementia (33–35) … study members with advanced Biological Age had older retinal vessels (narrower arterioles, r = −0.20, P < 0.001; wider venules, r = 0.17, P < 0.001).”

“… these biologically older study members were perceived to be older by independent observers.”

“Based on Pace of Aging analysis, we estimate that roughly 1/2 of the difference in Biological Age
observed at chronological age 38 had accumulated over the past 12 y.”

“… our analysis was limited to a single cohort, and one that lacked ethnic minority populations. Replication in other cohorts is needed, in particular in samples including sufficient numbers of ethnic minority individuals to test the “weathering hypothesis” that the stresses of ethnic minority status accelerate aging.”

“Three Dunedin Study members had Pace of Aging less than zero, appearing to grow physiologically younger during their thirties.”

While I suspect measurement error is at play, I’d still like to know what those guys did.