Gender, aging and longevity in humans


Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene–environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type 2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence.

On the whole, gender differences appear to be pervasive and still poorly considered and investigated despite their biomedical relevance. The basic biological mechanisms responsible for gender differences in aging and longevity are quite complex and still poorly understood. This review focuses on centenarians and their offspring as a model of healthy aging and summarizes available knowledge on three basic biological phenomena, i.e. age-related X chromosome inactivation skewing, gut microbiome changes and maternally inherited mitochondrial DNA genetic variants.

In conclusion, an appropriate gender-specific medicine approach is urgently needed and should be systematically pursued in studies on healthy aging, longevity and age-related diseases, in a globalized world characterized by great gender differences which have a high impact on health and diseases.

FULL TEXT: Clinical Science



Cell division plays a critical role in the normal growth, maintenance and repair of human tissue. Telomeres are repeated sequences of DNA at the ends of each chromosome, and are key genetic elements involved with the regulation of cell division. Telomeres shorten every time a cell divides, and once telomeres reach a critically short length, the cell either dies by apoptosis or stops dividing and senesces.

Telomerase is a naturally occurring enzyme that maintains telomeres and prevents them from shortening during cell division. Telomerase consists of at least two essential components: an RNA template, which binds to the telomere, and a catalytic subunit with reverse transcriptase activity, which adds the specific DNA sequence to the chromosome ends each time a cell divides.



Telomeres shorten …

A telomere is the end of a chromosome. Telomeres are made of repetitive sequences of non-coding DNA that protect the chromosome from damage. Each time a cell divides, the telomeres become shorter. Eventually, the telomeres become so short that the cell can no longer divide.


A reverse transcriptase

Telomerase is a special reverse transcriptase that carries its own RNA template (ribonucleoprotein) and can elongate telomeres. It has a strong presence in frequently dividing cells (to prevent loss of function). It is not present in all cells. Telomerase activity is enhanced in cancer cells.

Growth factors + aging


Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long-lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes.

These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6,000 US subjects in the NHANES CDC database.

Respondents aged 50–65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3–4 fold increased risk of cancer mortality and these findings were confirmed in mouse studies. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases.

FULL TEXT: Growth Hormone IGF Research