When it comes to development there are a number of steps which can be quite well defined. One, of course, is death. Another is birth. Then there is sexual maturity and for some people menopause.
There are plenty of papers which link precocious puberty with early menopause. There are also those which link early menopause with higher mortality and earlier age based diseases. This points to those being driven by the mRNA splicing changes and other changes in mRNA transcription primarily from the average mitochondrial membrane potential.
I was wondering recently, however, about birth. Is that step potentially driven by MMP. There are a number of pieces of evidence that point to this. One is that mothers who were born prematurely are also likely to have premature children. Importantly people who are born prematurely also face health problems in their lives at an earlier stage.
An overview of adult health outcomes after preterm birth
" Large cohort studies have shown that among persons born in the modern neonatal care era who survived to adulthood (≥18 years), those born preterm had approximately 30% to 50% higher all-cause mortality in early to mid-adulthood (ages ranging from 18 to 45 years) than those born full-term [9]. A recent systematic review [9] identified 7 published studies (5 in Sweden [6,7,[10], [11], [12]], 1 in Norway [13], and 1 in Australia [14]) that examined preterm birth in relation to all-cause mortality in adulthood. After adjusting for other perinatal and sociodemographic factors, most relative risks were in the 1.2 to 1.6 range [9].
The largest study to date included >4 million persons born as singletons in Sweden during 1973–2015 who were followed up through 2017 (including >2.5 million who reached adult ages) [6]. All-cause mortality in adulthood was assessed separately at ages 20–29 and 30–45 years. Adjusted hazard ratios (HRs) for all-cause mortality associated with preterm birth among women and men, respectively, were 1.54 (95% CI, 1.31–1.82; P < 0.001) and 1.32 (1.20–1.46; P < 0.001) at ages 20–29 years, and 1.55 (1.28–1.89; P < 0.001) and 1.17 (1.01–1.34; P = 0.03) at ages 30–45 years, compared with full-term birth (39–41 weeks). Extremely preterm birth (22–27 weeks) was associated with 2-fold mortality at ages 20–29 or 30–45 years. Most HRs were higher among women because of lower background mortality in those born at term compared with men. However, preterm birth accounted for significantly more total deaths among men (additive interaction, P < 0.001). In addition, a co-sibling analysis to control for unmeasured shared familial factors in 3.5 million persons with at least one sibling showed minimal change in risk estimates, suggesting that the observed associations were not due to confounding by shared genetic or environmental factors in families [6]. Fig. 1 shows the adjusted HRs for all-cause mortality from birth to age 45 years associated with gestational age at birth in this large cohort [6].
This fits with the hypothesis that average mitochondrial efficiency lies behind this. A critical test, therefore, is what happens when efforts are made to prevent a pre-term birth. Does that have a long term health benefit or in fact is it not treating the underlying problem and hence does not benefit the child to the same extent.
Medical and Pregnancy Conditions Associated with Preterm Birth
"Family History and Spontaneous Preterm Birth Several observations support the hypothesis that spontaneous preterm birth is influenced by a family history of preterm birth. First, evidence from two studies performed with twins suggests a genetic predisposition for preterm birth with estimates of the proportion of preterm births among women with a family history of preterm birth ranging from 20 to 40 percent (Blackmore-Prince et al., 2000; Fuentes-Afflick and Hessol, 2000). Other observations support the idea that genetic factors affect the risk of preterm birth: (1) the leading risk factor for preterm birth is a previous preterm birth (James et al., 1999; Klerman et al., 1998; Shults et al., 1999); (2) an association between race-ethnicity and preterm birth persists in some instances, even if it is corrected for socioeconomic condition (Ekwo and Moawad, 1998); and (3) mothers who were preterm themselves (Basso et al., 1998) or who have a sister who had delivered an infant preterm (Kallan, 1997) have an increased risk of delivering their infants preterm."
I think it is clear that puberty is affected by MMP. The fact that Melatonin operates to hold back puberty tends to support this. Melatonin is a good tool for preventing mitochondrial DNA damage.
Contrary to this hypothesis, however, there is mixed evidence linking Puberty with Premature birth.
Preterm birth and the timing of puberty: a systematic review
Results
Our search identified 1051 studies, of which 16 met the inclusion criteria. In females, 8 studies found no association between preterm birth and the timing of menarche. Five studies found earlier onset in preterm infants, 1 found later onset, and 1 showed both earlier and later menarche, depending on birth weight. The range of effect of studies showing earlier menarche was - 0.94 to −0.07 years in the preterm group, with a median of - 0.3 years. In males, 2 studies showed earlier onset of puberty in the preterm group, 5 showed no difference, and 1 showed later onset. Most studies did not present outcomes in the form of a mean with standard deviation, precluding a meta-analysis. There was insufficient data to address potential confounding factors.
Conclusions
The published evidence does not suggest that being born preterm leads to a significant acceleration in the onset of puberty. This should prove reassuring for public health purposes, and for clinicians counseling parents of infants born preterm.
There are plenty of papers which link precocious puberty with early menopause. There are also those which link early menopause with higher mortality and earlier age based diseases. This points to those being driven by the mRNA splicing changes and other changes in mRNA transcription primarily from the average mitochondrial membrane potential.
I was wondering recently, however, about birth. Is that step potentially driven by MMP. There are a number of pieces of evidence that point to this. One is that mothers who were born prematurely are also likely to have premature children. Importantly people who are born prematurely also face health problems in their lives at an earlier stage.
An overview of adult health outcomes after preterm birth
" Large cohort studies have shown that among persons born in the modern neonatal care era who survived to adulthood (≥18 years), those born preterm had approximately 30% to 50% higher all-cause mortality in early to mid-adulthood (ages ranging from 18 to 45 years) than those born full-term [9]. A recent systematic review [9] identified 7 published studies (5 in Sweden [6,7,[10], [11], [12]], 1 in Norway [13], and 1 in Australia [14]) that examined preterm birth in relation to all-cause mortality in adulthood. After adjusting for other perinatal and sociodemographic factors, most relative risks were in the 1.2 to 1.6 range [9].
The largest study to date included >4 million persons born as singletons in Sweden during 1973–2015 who were followed up through 2017 (including >2.5 million who reached adult ages) [6]. All-cause mortality in adulthood was assessed separately at ages 20–29 and 30–45 years. Adjusted hazard ratios (HRs) for all-cause mortality associated with preterm birth among women and men, respectively, were 1.54 (95% CI, 1.31–1.82; P < 0.001) and 1.32 (1.20–1.46; P < 0.001) at ages 20–29 years, and 1.55 (1.28–1.89; P < 0.001) and 1.17 (1.01–1.34; P = 0.03) at ages 30–45 years, compared with full-term birth (39–41 weeks). Extremely preterm birth (22–27 weeks) was associated with 2-fold mortality at ages 20–29 or 30–45 years. Most HRs were higher among women because of lower background mortality in those born at term compared with men. However, preterm birth accounted for significantly more total deaths among men (additive interaction, P < 0.001). In addition, a co-sibling analysis to control for unmeasured shared familial factors in 3.5 million persons with at least one sibling showed minimal change in risk estimates, suggesting that the observed associations were not due to confounding by shared genetic or environmental factors in families [6]. Fig. 1 shows the adjusted HRs for all-cause mortality from birth to age 45 years associated with gestational age at birth in this large cohort [6].
This fits with the hypothesis that average mitochondrial efficiency lies behind this. A critical test, therefore, is what happens when efforts are made to prevent a pre-term birth. Does that have a long term health benefit or in fact is it not treating the underlying problem and hence does not benefit the child to the same extent.
Medical and Pregnancy Conditions Associated with Preterm Birth
"Family History and Spontaneous Preterm Birth Several observations support the hypothesis that spontaneous preterm birth is influenced by a family history of preterm birth. First, evidence from two studies performed with twins suggests a genetic predisposition for preterm birth with estimates of the proportion of preterm births among women with a family history of preterm birth ranging from 20 to 40 percent (Blackmore-Prince et al., 2000; Fuentes-Afflick and Hessol, 2000). Other observations support the idea that genetic factors affect the risk of preterm birth: (1) the leading risk factor for preterm birth is a previous preterm birth (James et al., 1999; Klerman et al., 1998; Shults et al., 1999); (2) an association between race-ethnicity and preterm birth persists in some instances, even if it is corrected for socioeconomic condition (Ekwo and Moawad, 1998); and (3) mothers who were preterm themselves (Basso et al., 1998) or who have a sister who had delivered an infant preterm (Kallan, 1997) have an increased risk of delivering their infants preterm."
I think it is clear that puberty is affected by MMP. The fact that Melatonin operates to hold back puberty tends to support this. Melatonin is a good tool for preventing mitochondrial DNA damage.
Contrary to this hypothesis, however, there is mixed evidence linking Puberty with Premature birth.
Preterm birth and the timing of puberty: a systematic review
Results
Our search identified 1051 studies, of which 16 met the inclusion criteria. In females, 8 studies found no association between preterm birth and the timing of menarche. Five studies found earlier onset in preterm infants, 1 found later onset, and 1 showed both earlier and later menarche, depending on birth weight. The range of effect of studies showing earlier menarche was - 0.94 to −0.07 years in the preterm group, with a median of - 0.3 years. In males, 2 studies showed earlier onset of puberty in the preterm group, 5 showed no difference, and 1 showed later onset. Most studies did not present outcomes in the form of a mean with standard deviation, precluding a meta-analysis. There was insufficient data to address potential confounding factors.
Conclusions
The published evidence does not suggest that being born preterm leads to a significant acceleration in the onset of puberty. This should prove reassuring for public health purposes, and for clinicians counseling parents of infants born preterm.
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