The full benefits of senescence are achieved when the process
includes the clearance of the senescent cells, thereby restoring the
pre-damage status of the tissue. However, in chronic pathological
situations such as aging (as modelled by
tert
−
/
−
fish), cardiac
regeneration is impaired and a fibrotic scar remains. This inability to
regenerate is primarily due to a strong inhibition of the proliferative
response and an accumulation of senescent cells that becomes
persistent, and these cells even extend beyond the injured area,
further aggravating tissue dysfunction (Bednarek et al., 2015)
(Fig. 3B). The difficulty in handling and clearing damaged and
senescent cells could overload the tissue with SASP. This effect
results in a persistent chronic inflammatory microenvironment that
further aggravates tissue dysfunction and impairs proper
regeneration. This process might not be applicable to other types
of aged tissues, but constitutes a clear example of how short
telomeres and cellular senescence can contribute to age-related
defects in tissue regeneration.
Senescence is a double-edged sword, beneficial when it is
transient and easily handled but pathological when chronic and
unresolved. So, what makes an aged tissue more prone to the
accumulation of senescent cells? On the one hand, clearance of
senescent cells by the immune system might become impaired with
aging, leading to a net accumulation of senescent cells that further
aggravate tissue dysfunction via the SASP
Modern society is extremely interested in finding ways to extend
human healthy lifespan. There are ongoing pharmacological tests
and biological therapies to prevent telomere shortening and
accumulation of senescent cells during aging. The impact this will
have on human health and disease is currently unknown, although it
will likely reveal new biological phenomena. If shortening of
telomeres can be prevented and/or senescent cells can be eliminated
in human tissues, will this simply delay the very familiar aging
phenomenon, or will new types of pathology emerge? These
nuances and complexities demand further investigation in order to
guide potential new therapeutic options.
Why don't you ever read the papers you post beyond the title?
There is little in the paper in counter-argument to SENS therapies. If anything, they would very much like to see them tested.